Diaminopyrazolo[1,5-a]pyrimidine-6-carbonitrile compounds as adenosine 2a receptor and adenosine 2b receptor antagonist

Abstract

The present disclosure provides a compound of Formula I or its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, stereoisomers, racemates, pharmaceutically active derivatives thereof. The compounds of Formula I act as antagonists to adenosine receptors. The present disclosure also provides a process for preparation of compounds of Formula I and pharmaceutical composition thereof. [Image disponible dans le document PDF, Image available in the PDF document]

Description

DIAMINOPYRAZOLO[1,5-a]PYRIMIDINE-6-CARBONITRILE COMPOUNDS AS ADENOSINE 2A RECEPTOR AND ADENOSINE 2B RECEPTOR ANTAGONIST FIELD OF INVENTION

[0001] The present disclosure relates to the field of medicinal chemistry and particularly to the development of heterocyclic compounds and a process of preparation of the same. The present disclosure more particularly to the pyrazolopyrimidine compounds and in particular diaminopyrazolopyrimidine compounds which act as antagonists for adenosine receptors. BACKGROUND

[0002] Adenosine is a purine nucleoside produced by cells for its intracellular physiological and extracellular signaling processes. It is synthesized from inosine monophosphate (IMP) as a nucleotide from adenosine monophosphate (AMP) or by the hydrolysis of adenosine triphosphate (ATP) via adenosine diphosphate (ADP) and AMP. Apart from being one of the building blocks of DNA, it is the primary energy source of cells as adenosine triphosphate (ATP) and is involved in the all-pervasive signal transduction processes as cyclic adenosine monophosphate (cAMP). Extracellular adenosine regulates inflammation, allostasis and cognitive functions in the brain, and vasodilation in the heart, lungs, and kidneys, all brought about by its binding to the adenosine receptors.

[0003] Adenosine receptors are members of the guanine nucleotide protein-coupled receptors (GPCR) family on the cell surface and consist of A1R, A2aR, A2bR, and A3R subtypes in humans (Jacobson et al., 2012, PMID: 22371149). A1 and A3 receptor couple to Gai / o, in contrast, A2a and A2b receptors couple to Gas to inhibit or stimulate adenylate cyclase (AC) respectively and are distributed ubiquitously throughout the body (Borea et al., 2018, DOI: 10.1007 / 978-3-319-90808-3; Cheng et al., 2017, PMID: 28712806). Their agonist or antagonist ligands are used as pharmacological interventions of various pro- and anti-inflammatory mediators to manage asthma, chronic pulmonary obstructive disease, heart failure, arrhythmia, diabetic kidney disease, glaucoma, stroke, sleep, anxiety, neurodegenerative disorders like Parkinson's, Alzheimer's and Huntington's diseases, epilepsy, pain, cognition and memory, and cancer (Sek et al., 2018, PMID: 30513816).

[0004] During infection, injury, hypoxia, ischemia, or seizure, extracellular adenosine is upregulated in tissues as an allostatic measure to protect tissue damage from the inflammatory responses. Similar immunosuppressive mechanisms of elevated adenosine levels (in the tumor micro-environment, TME) have been identified in tumor immune evasion. In the TME, adenosine binds to <semantics>A2aR<annotation encoding="application / x-tex">A_{2a}R< / annotation>< / semantics> and <semantics>A2bR<annotation encoding="application / x-tex">A_{2b}R< / annotation>< / semantics> on various immune cells and suppresses them by activating the cAMP-dependent Protein Kinase A (PKA) and blockade of the nuclear factor-kB (NF-kB) and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway (Allard et al., 2020, PMID: 32514148). Relieving this inhibition of the A2aR and A2bR by selective antagonists can make the immune cells capable of killing tumor cells (Vijayan et al., 2017; PMID: 29162946, Allard et al., 2020, PMID: 32514148). Thus, in the present scenario of increasing proliferative disorders, or diseases or conditions, there is a huge need for antagonists of adenosine receptors. Hence there is a huge need for the antagonists of adenosine receptors, which will be useful in treating condition related to cancer or immune- related disorders mediated by these receptors. SUMMARY OF THE INVENTION

[0005] In an aspect of the present disclosure, there is provided a compound of Formula I [Image disponible dans le document PDF, Image available in the PDF document] Formula I or its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, stereoisomers, racemates, pharmaceutically active derivatives thereof, wherein A is selected from <semantics>C5−10<annotation encoding="application / x-tex">C_{5-10}< / annotation>< / semantics> aryl, <semantics>C2−10<annotation encoding="application / x-tex">C_{2-10}< / annotation>< / semantics> heteroaryl, <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl; wherein <semantics>C5−10<annotation encoding="application / x-tex">C_{5-10}< / annotation>< / semantics> aryl, <semantics>C2−10<annotation encoding="application / x-tex">C_{2-10}< / annotation>< / semantics> heteroaryl, <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl is optionally substituted with one or more substituents selected from <semantics>R6,R7,R8,R9,R9a<annotation encoding="application / x-tex">R_6, R_7, R_8, R_9, R_{9a}< / annotation>< / semantics> or oxo; <semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics> is selected from hydrogen, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics> alkenyl, <semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics> alkynyl, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl; <semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics> is selected from hydrogen, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics> alkenyl, <semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics> alkynyl, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl; wherein <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl is optionally substituted with <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy; R4 and R5 are independently selected from hydrogen, halogen, cyano, C1-6 alkyl, C2- 6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, -CO-N(<semantics>R10<annotation encoding="application / x-tex">R_{10}< / annotation>< / semantics> <semantics>R11<annotation encoding="application / x-tex">R_{11}< / annotation>< / semantics>), <semantics>C4−10<annotation encoding="application / x-tex">C_{4-10}< / annotation>< / semantics> carbocyclyl, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl, wherein <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics> alkenyl or <semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics> alkynyl are optionally substituted with one or more groups selected from <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl; or <semantics>R4<annotation encoding="application / x-tex">R_4< / annotation>< / semantics> and <semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics> are joined together to form <semantics>C4−10<annotation encoding="application / x-tex">C_{4-10}< / annotation>< / semantics> carbocyclyl, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl, wherein <semantics>C4−10<annotation encoding="application / x-tex">C_{4-10}< / annotation>< / semantics> carbocyclyl or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl is optionally substituted with 1 to 3 groups independently selected from halogen, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy; R10 and R11 are independently selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-1 6 alkynyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkyl, C3-6 halocycloalkyl, C4-10 carbocyclyl, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl; <semantics>R6<annotation encoding="application / x-tex">R_6< / annotation>< / semantics> is selected from hydrogen, halogen, hydroxyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl, <semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics> alkenyl, <semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics> alkynyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkylhydroxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> aminoalkyl, C3-6 cycloalkyl, C3-6 halocycloalkyl, -Y-O-C1-6 alkyl, -Y-O-C3-6 cycloalkyl, -Y-CO-NH-R13, -Y-Z, C4-10 carbocyclyl, or C1-10 heterocyclyl, wherein <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> aminoalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkylhydroxy, or C1-10 heterocyclyl is optionally substituted with one or more groups selected from halogen, hydroxyl, amine, C1-6 alkoxy, C3-6 cycloalkyl, C1-6 alkylhydroxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> aminoalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy, <semantics>C4−10<annotation encoding="application / x-tex">C_{4-10}< / annotation>< / semantics> carbocyclyl, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl, wherein <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> aminoalkyl, is optionally further substituted with one or more groups independently selected from halogen, hydroxyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkylhydroxy, <semantics>−C(O)C1−6<annotation encoding="application / x-tex">-C(O)C_{1-6}< / annotation>< / semantics> alkyl, <semantics>−C(O)NH2<annotation encoding="application / x-tex">-C(O)NH_2< / annotation>< / semantics>, <semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics> alkylhydroxy, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl, and <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl has 1 to 4 heteroatoms independently selected from O, N or S, and optionally substituted with 1 to 3 groups independently selected from halogen, hydroxyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy; Y is selected from <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics> alkenyl, <semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics> alkynyl, <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, or <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkenyl; and <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl is optionally substituted with <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl; Z is selected from -OH, -NH2, -COOH, -SO2NH2, -SO2CH3, -SOCH3, -SCH3, CH2- <semantics>NH−(C1−6 alkyl)−SOCH3<annotation encoding="application / x-tex">NH-(C_{1-6} \text{ alkyl})-SOCH_3< / annotation>< / semantics>, <semantics>−O−P(=O)(OH)2<annotation encoding="application / x-tex">-O-P(=O)(OH)_2< / annotation>< / semantics>, <semantics>−CONH2<annotation encoding="application / x-tex">-CONH_2< / annotation>< / semantics>, <semantics>−CONH(C1−6 alkyl)<annotation encoding="application / x-tex">-CONH(C_{1-6} \text{ alkyl})< / annotation>< / semantics>, <semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics> <semantics>SO2NH(C1−6 alkyl)<annotation encoding="application / x-tex">SO_2NH(C_{1-6} \text{ alkyl})< / annotation>< / semantics>, <semantics>CON(C1−6 alkyl)2<annotation encoding="application / x-tex">CON(C_{1-6} \text{ alkyl})_2< / annotation>< / semantics>, <semantics>−NHCO(C1−6 alkyl)<annotation encoding="application / x-tex">-NHCO(C_{1-6} \text{ alkyl})< / annotation>< / semantics>, <semantics>C4−10<annotation encoding="application / x-tex">C_{4-10}< / annotation>< / semantics> carbocyclyl, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> 10 heterocyclyl, wherein <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl has 1 to 4 heteroatoms independently selected from O, N or S, and optionally substituted with 1 to 3 groups independently selected from halogen, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy; R13 is selected from hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, or C3-6 halocycloalkyl; <semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>, <semantics>R8<annotation encoding="application / x-tex">R_8< / annotation>< / semantics>, <semantics>R9<annotation encoding="application / x-tex">R_9< / annotation>< / semantics>, and <semantics>R9a<annotation encoding="application / x-tex">R_{9a}< / annotation>< / semantics> are independently selected from hydrogen, halogen, cyano, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy, or <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> halocycloalkyl; and n is 0, 1, or 2.

[0006] In another aspect of the present disclosure, there is provided a process of preparation of compounds of Formula I or its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, stereoisomers, racemates, pharmaceutically active derivatives thereof, said process comprising: reacting Formula (A), and Formula (B) in the presence of a base to obtain the compounds of Formula I, [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] + Formula (A) Formula (B) Formula (I) wherein R is selected from <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, <semantics>C5−10<annotation encoding="application / x-tex">C_{5-10}< / annotation>< / semantics> aryl, <semantics>C2−10<annotation encoding="application / x-tex">C_{2-10}< / annotation>< / semantics> heteroaryl, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl; and the substituents are as defined above.

[0007] In one another aspect of the present disclosure, there is provided a pharmaceutical composition comprising a compound of Formula I as disclosed herein and one or more additional therapeutic agents.

[0008] In yet another aspect of the present disclosure, there is provided a method of treatment and / or prevention of a condition mediated by adenosine receptor or a proliferative disorder or cancer, comprising administering to a subject suffering from a condition mediated by adenosine receptor or a disease or proliferative disorder or cancer, a therapeutically effective amount of the compounds of Formula I as disclosed herein or the pharmaceutical composition comprising compounds of Formula I as disclosed herein and one or more additional therapeutic agent.

[0009] In further another aspect of the present disclosure, there is provided use of the compounds as disclosed herein or the pharmaceutical composition as disclosed herein for treatment of a condition mediated by adenosine receptor <semantics>A2aR<annotation encoding="application / x-tex">A_{2a}R< / annotation>< / semantics>, or <semantics>A2bR<annotation encoding="application / x-tex">A_{2b}R< / annotation>< / semantics>; treatment and / or prevention of a proliferative disorder or disease or cancer or immune-related disorder or disease or condition; or treatment of cancer together with other clinically relevant cytotoxic agents or non-cytotoxic agents.

[00010] In furthermore aspect of the present disclosure, there is provided use of the compounds as disclosed herein or the pharmaceutical composition as disclosed herein for treatment of a condition mediated by adenosine receptors <semantics>A2aR<annotation encoding="application / x-tex">A_{2a}R< / annotation>< / semantics> and <semantics>A2bR<annotation encoding="application / x-tex">A_{2b}R< / annotation>< / semantics>; treatment and / or prevention of a proliferative disorder or disease or cancer or immune-related disorder or disease or condition; or treatment of cancer together with other clinically relevant cytotoxic agents or non-cytotoxic agents.

[00011] These and other features, aspects, and advantages of the present subject matter will become better understood with reference to the following description. This summary is provided to introduce a selection of concepts in a simplified form. This summary is not intended to identify key features or essential features of the disclosure, nor is it intended to be used to limit the scope of the subject matter. BRIEF DESCRIPTION OF THE DRAWINGS

[00012] Figure 1 depicts the in vivo efficacy effect of Example-13 on Tumor volume, in accordance with an implementation of the present disclosure.

[00013] Figure 2 depicts Tumor Granzyme B expression compared to vehicle treatment in accordance with an implementation of the present disclosure. DETAILED DESCRIPTION

[00014] Those skilled in the art will be aware that the present disclosure is subject to variations and modifications other than those specifically described. It is to be understood that the present disclosure includes all such variations and modifications. The disclosure also includes all such steps, features, compositions, and compounds referred to or indicated in this specification, individually or collectively, and any combinations of any or more of such steps or features. Definitions

[00015] For convenience, before further description of the present disclosure, certain terms employed in the specification, and examples are collected here. These definitions should be read in the light of the remainder of the disclosure and understood as by a person of skill in the art. The terms used herein have the meanings recognized and known to those of skill in the art, however, for convenience and completeness, particular terms and their meanings are set forth below.

[00016] The articles "a", "an" and "the" are used to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article.

[00017] The terms "comprise" and "comprising" are used in the inclusive, open sense, meaning that additional elements may be included. Throughout this specification, unless the context requires otherwise the word "comprise", and variations, such as "comprises" and "comprising", will be understood to imply the inclusion of a stated element or step or group of element or steps but not the exclusion of any other element or step or group of element or steps.

[00018] The term "including" is used to mean "including but not limited to". "Including" and "including but not limited to" are used interchangeably.

[00019] In the structural Formulae given herein and throughout the present disclosure, the following terms have been indicated meaning, unless specifically stated otherwise.

[00020] In this specification, the prefix <semantics>Cx−y<annotation encoding="application / x-tex">C_{x-y}< / annotation>< / semantics> as used in terms such as <semantics>Cx−y<annotation encoding="application / x-tex">C_{x-y}< / annotation>< / semantics> alkyl and the like (where x and y are integers) indicates the numerical range of carbon atoms that are present in the group; for example, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>alkyl includes <semantics>C1<annotation encoding="application / x-tex">C_{1}< / annotation>< / semantics>alkyl (methyl(-CH3), (-CH2-)), <semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>alkyl (ethyl(-<semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>H5, -CH2CH2-)), <semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>alkyl (propyl and isopropyl) and C4alkyl (butyl, 1-methylpropyl, 2-methylpropyl, and t-butyl). Unless specifically stated, the bonding atom of a group may be any suitable atom of that group; for example, propyl includes prop-1-yl and prop-2-yl.

[00021] The term "alkyl" refers to a monoradical branched or unbranched saturated hydrocarbon chain having from 1 to 6 carbon atoms. This term is exemplified by groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, t-butyl, n-hexyl, and the like. The groups may be optionally substituted.

[00022] The term "haloalkyl" as used herein refers to an alkyl group in which one or more hydrogen atoms are replaced by the same number of identical or different halogen atoms. The term "haloalkyl" is exemplified by groups such as chloromethyl, trifluoromethyl, 1-fluoroethyl, 2,2,2-trifluoroethyl, 2-fluoropropyl, 2,2-difluoropropyl, and the like. The term haloalkyl is exemplified by groups such as CF3, CHF2, CH2F, and the like.

[00023] The term "aminoalkyl" refers to a group having an amine and an alkyl group and the amine may be primary, secondary or tertiary amine. The point of attachment may be N or C i.e amine or alkyl group. The term "aminoalkyl" and "alkylamino" may be used interchangeably. The term aminoalkyl is exemplified by groups such as <semantics>−CH(CH3)2NH2<annotation encoding="application / x-tex">-CH(CH_3)_2NH_2< / annotation>< / semantics>, <semantics>−CH2CH2NH2<annotation encoding="application / x-tex">-CH_2CH_2NH_2< / annotation>< / semantics>, <semantics>−CH2CH2NHCH3<annotation encoding="application / x-tex">-CH_2CH_2NHCH_3< / annotation>< / semantics>, <semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics> CH2CH(NH2)CH3, -CH2CH2N(CH3)2, -NHCH3, -N(CH3)2, -CH2NH2, -CH2NHCH3, -CH2NHCH2-, -CH2NHCH2CH2- and the like.

[00024] The term "alkylhydroxy" or "alkylhydroxyl" refers to an alkyl group in which one or more hydrogen atoms are replaced by a hydroxyl(-OH) group. The term alkylhydroxy is exemplified by groups such as -CH2CH(CH3)2OH, - CH(CH3)2OH, -CH2OH, CH2CH2OH and the like.

[00025] The term "alkenyl" refers to a monoradical of a branched or unbranched unsaturated hydrocarbon group preferably having from 2, 3, 4, 5, or 6 carbon atoms and having 1, 2, or 3, double bond. The groups may be optionally substituted.

[00026] The term "alkynyl" refers to a monoradical of a branched or unbranched unsaturated hydrocarbon group preferably having from 2, 3, 4, 5, or 6 carbon atoms and having 1, 2, or 3, triple bond. The groups may be optionally substituted.

[00027] The term "cycloalkyl" refers to carbocyclic groups with 3 to 6 carbon atoms having a single cyclic ring or multiple condensed rings. Such cycloalkyl groups include, by way of example, single ring structures such as cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, and the like. The groups may be optionally substituted.

[00028] The term "cycloalkenyl" refers to carbocyclic groups of 3 to 6 carbon atoms having a single cyclic ring or multiple condensed rings which may be partially unsaturated.

[00029] The term "halocycloalkyl" as used herein refers to a cycloalkyl substituted with one or more halogen atoms. The halocycloalkyl refers to 3 to 6 carbon containing cycloalkyl substituted with one or more halogens.

[00030] The terms "alkoxyl" or "alkoxy" refers to an alkyl group, as defined above, having an oxygen radical attached thereto. Representative alkoxyl groups include methoxy, ethoxy, propyloxy, tert-butoxy, and the like. An "ether" is two hydrocarbons covalently linked by an oxygen. Accordingly, the substituent of an alkyl that renders an ether is or resembles an alkoxyl, such as can be represented by one of -O-alkyl, -O- alkenyl, -O-alkynyl. The alkoxy groups may be optionally substituted.

[00031] "Halo" or "Halogen", alone or in combination with any other term means halogens such as chloro (Cl), fluoro (F), bromo (Br) and iodo (I).

[00032] The term "carbocyclyl" or "carbocycle" refers to a saturated, unsaturated ring having 4 to 10 carbon atoms forming cyclic systems. Carbocyclic groups may be spiral or bridged systems, may be saturated, unsaturated or partially saturated. Carbocyclyl groups may be optionally substituted with one or more heteroatoms. Carbocyclic groups may refer to heteroaryl groups with one or more heteroatoms. Representative carbocycles include cyclopropyl, cyclobutyl, cyclopentyl, 1-cyclopent-1-enyl, 1-cyclopent-2-enyl, 1-cyclopent-3-enyl, cyclohexyl, 1-cyclohex-1-enyl, 1-cyclohex-2-enyl, 1-cyclohex-3-enyl, and the like.

[00033] The term "heterocyclyl" refers to a "carbocyclyl" as defined herein, wherein one or more carbon atoms have been replaced with a heteroatom selected from O, N, or S. The heterocyclyl group may contain 1 to 10 carbon in the ring structure, substituted with one to four heteroatoms selected from O, N, or S. The heterocyclyl may be saturated, unsaturated or partially saturated. Representative examples of heterocyclyl include oxiranyl, oxetanyl, oxolanyl, oxanyl, furanyl, dioxanyl, pyranyl, aziridinyl, piperidinyl, tetrahydropyranyl, azepinyl, oxazepinyl and the like.

[00034] The term "heteroaryl" refers to aromatic rings containing from 1 to 4 heteroatoms selected from N, O and S in the ring. "Heteroaryl" groups may be substituted with one or more substituents if so defined herein. The "C2-6 heteroaryl" rings refers to a group having 2 or 6 carbon as ring member atoms with one to four heteroatoms.

[00035] The term "aryl" refers to aromatic ring having a specified number of carbon atoms. For example, <semantics>C5−10<annotation encoding="application / x-tex">C_{5-10}< / annotation>< / semantics> aryl refers to an aryl group having 5 to 10 member atoms, or 6 member atoms. Preferred aryl groups include, without limitation, phenyl, and the like.

[00036] The term "haloalkoxy" refers to an alkoxy group as defined above further attached via halo linkage. For example, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy refers to an alkoxy group having <semantics>1−6<annotation encoding="application / x-tex">1-6< / annotation>< / semantics> carbon atoms further attached to one or more halogen. Preferred haloalkoxy groups include, without limitation, -CH2OCF3, -CH2CH2OCF3, - CH2CH2OCHF2, -OCH2Cl, -OCHCl2, -CH2OCF3 and the like.

[00037] As used herein, the term "substituted" is contemplated to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and nonaromatic substituents of organic compounds. Illustrative substituents include, for example, those described herein above. The permissible substituents can be one or more and the same or different for appropriate organic compounds. For purposes of this disclosure, the heteroatoms such as nitrogen may have hydrogen substituents and / or any permissible substituents of organic compounds described herein which satisfy the valences of the heteroatoms.

[00038] The term "effective amount" means an amount of a compound or composition which is sufficient enough to significantly and positively modify the symptoms and / or conditions to be treated (e.g., provide a positive clinical response). The effective amount of an active ingredient for use in a pharmaceutical composition will vary with the particular condition being treated, the severity of the condition, the duration of the treatment, the nature of concurrent therapy, the particular active ingredient(s) being employed, the particular pharmaceutically- acceptable excipient(s) / carrier(s) utilized, the route of administration, and like factors within the knowledge and expertise of the attending physician.

[00039] The compounds described herein may contain one or more chiral centers and / or double bonds and therefore, may exist as stereoisomers, such as double-bond isomers (i.e., geometric isomers), regioisomers, enantiomers, or diastereomers. Accordingly, the chemical structures depicted herein encompass all possible enantiomers and stereoisomers of the illustrated or identified compounds including the stereoisomerically pure form (e.g., geometrically pure, enantiomerically pure or diastereomerically pure) and enantiomeric and stereoisomeric mixtures. Enantiomeric and stereoisomeric mixtures can be resolved into their component enantiomers or stereoisomers using separation techniques or chiral synthesis techniques well known to the person skilled in the art. The compounds may also exist in several tautomeric forms including the enol form, the keto form, and mixtures thereof. Accordingly, the chemical structures depicted herein encompass all possible tautomeric forms of the illustrated or identified compounds.

[00040] The term "racemates" refers to a mixture comprising a pair of optical isomers. Racemate refers to equimolar mixture of a pair of enantiomers. Racemate does not exhibit optical activity.

[00041] The term "pharmaceutically acceptable" refers to those compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[00042] "Pharmaceutically acceptable salt" embraces salts with a pharmaceutically acceptable acid or base. Pharmaceutically acceptable acids include both inorganic acids, for example hydrochloric, sulphuric, phosphoric, diphosphoric, hydrobromic, hydroiodic and nitric acid and organic acids, for example citric, fumaric, maleic, malic, mandelic, ascorbic, oxalic, succinic, tartaric, benzoic, acetic, methanesulphonic, ethanesulphonic, benzenesulphonic or p- toluenesulphonic acid. Pharmaceutically acceptable bases include alkali metal (e.g. sodium or potassium) and alkali earth metal (e.g. calcium or magnesium) hydroxides and organic bases, for example alkyl amines, arylalkyl amines and heterocyclic amines.

[00043] The term "polymorphs" refers to crystal forms of the same molecule, and different polymorphs may have different physical properties such as, for example, melting temperatures, heats of fusion, solubilities, dissolution rates and / or vibrational spectra as a result of the arrangement or conformation of the molecules in the crystal lattice.

[00044] Salts and solvates having non-pharmaceutically acceptable counter- ions or associated solvents are within the scope of the present disclosure, for example, for use as intermediates in the preparation of other compounds of Formula I, and their pharmaceutically acceptable salts. Thus, one embodiment of the disclosure embraces compounds of Formula I, and salts thereof. Compounds according to and Formula I contain a basic functional group and are therefore capable of forming pharmaceutically acceptable acid addition salts by treatment with a suitable acid. Suitable acids include pharmaceutically acceptable inorganic acids and pharmaceutically acceptable organic acids. Representative pharmaceutically acceptable acid addition salts include hydrochloride, hydrobromide, nitrate, methylnitrate, sulfate, bisulfate, sulfamate, phosphate, acetate, hydroxyacetate, phenyl acetate, propionate, butyrate, iso-butyrate, valerate, maleate, hydroxymaleate, acrylate, fumarate, malate, tartrate, citrate, salicylate, glycollate, lactate, heptanoate, phthalate, oxalate, succinate, benzoate, o- acetoxybenzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, naphthoate, hydroxynaphthoate, mandelate, tannate, formate, stearate, ascorbate, palmitate, oleate, pyruvate, pamoate, malonate, laurate, glutarate, glutamate, estolate, methanesulfonate (mesylate), ethanesulfonate (esylate), 2-hydroxyethanesulfonate, benzenesulfonate (besylate), aminobenzenesulfonate, p- toluenesulfonate (tosylate), and naphthalene-2- sulfonate.

[00045] The term "solvate", as used herein, refers to a crystal form of a substance which contains solvent.

[00046] The term "complexes" as used herein, can be interchangeably used as "coordination complex," or "metal coordination complex," and the like. It refers to a complex of an organic compound with a metal that can be empirically differentiated from a simple metal salt of the organic compound based on physiochemical and / or spectroscopic properties, with a coordination complex typically having enhanced covalency as compared to a salt. Without limitation "complexes" as used herein also involve a combination of coordinate covalent bonds and / or ionic bonds. As used herein, the term "complexes" also includes molecules that lack an ionic component (e.g., such as a neutral coordination complex prior to deprotonation, where pKa of the coordination complex falls within a physiologically acceptable range).

[00047] The term "hydrate" refers to a solvate wherein the solvent is water.

[00048] A term once described, the same meaning applies for it, throughout the disclosure.

[00049] As discussed in the background, there has been enormous efforts for the identification and development of new compounds acting as antagonists for adenosine receptors for treating proliferative disorders or diseases or condition or diseases related to immune depression or cancer. Heterocyclic compounds have been found to act as such antagonists and in the present disclosure there is disclosed, compounds of Formula I, their synthetic preparation methods, and their biological activity towards the adenosine receptors. The compounds of Formula I are found to be adenosine receptor antagonists, in particular adenosine <semantics>A2aR<annotation encoding="application / x-tex">A_{2a}R< / annotation>< / semantics> and <semantics>A2bR<annotation encoding="application / x-tex">A_{2b}R< / annotation>< / semantics> receptor antagonists. The compounds of Formula I are suitably formulated with therapeutic agents to form the pharmaceutical composition. The pharmaceutical composition and the compounds of Formula I is used for the treatment of diseases or disorders or condition mediated by the adenosine receptors.

[00050] In an embodiment of the present disclosure, there is provided a compound of Formula I or its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, stereoisomers, racemates, pharmaceutically active derivatives thereof, [Image disponible dans le document PDF, Image available in the PDF document] Formula I wherein A is selected from <semantics>C5−10<annotation encoding="application / x-tex">C_{5-10}< / annotation>< / semantics> aryl, <semantics>C2−10<annotation encoding="application / x-tex">C_{2-10}< / annotation>< / semantics> heteroaryl, <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl; wherein <semantics>C5−10<annotation encoding="application / x-tex">C_{5-10}< / annotation>< / semantics> aryl, <semantics>C2−10<annotation encoding="application / x-tex">C_{2-10}< / annotation>< / semantics> heteroaryl, <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl is optionally substituted with one or more substituents selected from <semantics>R6<annotation encoding="application / x-tex">R_6< / annotation>< / semantics>, <semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>, <semantics>R8<annotation encoding="application / x-tex">R_8< / annotation>< / semantics>, <semantics>R9<annotation encoding="application / x-tex">R_9< / annotation>< / semantics>, <semantics>R9a<annotation encoding="application / x-tex">R_{9a}< / annotation>< / semantics> or oxo; <semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics> is selected from hydrogen, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics> alkenyl, <semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics> alkynyl, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl; <semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics> is selected from hydrogen, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics> alkenyl, <semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics> alkynyl, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl; wherein <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl is optionally substituted with <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy; R4 and R5 are independently selected from hydrogen, halogen, cyano, C1-6 alkyl, C2- 6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, -CO-N(<semantics>R10<annotation encoding="application / x-tex">R_{10}< / annotation>< / semantics> <semantics>R11<annotation encoding="application / x-tex">R_{11}< / annotation>< / semantics>), <semantics>C4−10<annotation encoding="application / x-tex">C_{4-10}< / annotation>< / semantics> carbocyclyl, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl, wherein <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics> alkenyl or <semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics> alkynyl are optionally substituted with one or more groups selected from <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl; or <semantics>R4<annotation encoding="application / x-tex">R_4< / annotation>< / semantics> and <semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics> are joined together to form <semantics>C4−10<annotation encoding="application / x-tex">C_{4-10}< / annotation>< / semantics> carbocyclyl, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl, wherein <semantics>C4−10<annotation encoding="application / x-tex">C_{4-10}< / annotation>< / semantics> carbocyclyl or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl is optionally substituted with 1 to 3 groups independently selected from halogen, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy; R10 and R11 are independently selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-1 6 alkynyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkyl, C3-6 halocycloalkyl, C4-10 carbocyclyl, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl; R6 is selected from hydrogen, halogen, hydroxyl, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, <semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics> alkynyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkylhydroxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> aminoalkyl, C3-6 cycloalkyl, C3-6 halocycloalkyl, -Y-O-C1-6 alkyl, -Y-O-C3-6 cycloalkyl, -Y-CO-NH-R13, -Y-Z, C4-10 carbocyclyl, or C1-10 heterocyclyl, wherein <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> aminoalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkylhydroxy, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl is optionally substituted with one or more groups selected from halogen, hydroxyl, amine, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkylhydroxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> aminoalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy, <semantics>C4−10<annotation encoding="application / x-tex">C_{4-10}< / annotation>< / semantics> carbocyclyl, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl, wherein <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> aminoalkyl, is optionally further substituted with one or more groups independently selected from halogen, hydroxyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkylhydroxy, <semantics>−C(O)C1−6<annotation encoding="application / x-tex">-C(O)C_{1-6}< / annotation>< / semantics> alkyl, <semantics>−C(O)NH2<annotation encoding="application / x-tex">-C(O)NH_2< / annotation>< / semantics>, <semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics> alkylhydroxy, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl, and <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl is optionally substituted with 1 to 3 groups independently selected from halogen, hydroxyl, C1-6 alkyl, C1-6 alkoxy, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy; Y is selected from <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics> alkenyl, <semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics> alkynyl, <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, or <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkenyl; and <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl is optionally substituted with <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl; Z is selected from -OH, -NH2, -COOH, -SO2NH2, -SO2CH3, -SOCH3, -SCH3, CH2- NH-<semantics>(C1−6 alkyl)<annotation encoding="application / x-tex">(C_{1-6} \text{ alkyl})< / annotation>< / semantics>-SOCH3, -O-P(=O)(OH)2, -CONH2, -CONH(C1-6 alkyl), - SO2NH(C1-6 alkyl), CON(C1-6 alkyl)2, -NHCO(C1-6 alkyl), C4-10 carbocyclyl, or C1- <semantics>10<annotation encoding="application / x-tex">10< / annotation>< / semantics> heterocyclyl, wherein <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl has 1 to 4 heteroatoms independently selected from O, N or S, and optionally substituted with 1 to 3 groups independently selected from halogen, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy; R13 is selected from hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, or C3-6 halocycloalkyl; R7, R8, R9, and R9a are independently selected from hydrogen, halogen, cyano, C1-6 alkyl, <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy, or <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> halocycloalkyl; and n is 0, 1, or 2.

[00051] In an embodiment of the present disclosure, there is provided a compound of Formula I or its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, stereoisomers, racemates, pharmaceutically active derivatives thereof, A is selected from <semantics>C5−10<annotation encoding="application / x-tex">C_{5-10}< / annotation>< / semantics> aryl, <semantics>C2−10<annotation encoding="application / x-tex">C_{2-10}< / annotation>< / semantics> heteroaryl, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl; <semantics>C5−10<annotation encoding="application / x-tex">C_{5-10}< / annotation>< / semantics> aryl, <semantics>C2−10<annotation encoding="application / x-tex">C_{2-10}< / annotation>< / semantics> heteroaryl, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl is optionally substituted with one or more substituents selected from R6, R7, R8, R9, <semantics>R9a<annotation encoding="application / x-tex">R_{9a}< / annotation>< / semantics>, or oxo; <semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics> is selected from hydrogen, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl; <semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics> is selected from hydrogen, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl and wherein <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl is optionally substituted with <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy; <semantics>R4<annotation encoding="application / x-tex">R_4< / annotation>< / semantics> and <semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics> are independently selected from hydrogen, halogen, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C1-6 alkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy, <semantics>C4−10<annotation encoding="application / x-tex">C_{4-10}< / annotation>< / semantics> carbocyclyl, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl, wherein <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> 6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, is optionally substituted with one or more groups selected from C3-6 cycloalkyl, C1-6 alkoxy, or C1-10 heterocyclyl; wherein C1- 10 heterocyclyl has 1 to 3 heteroatoms independently selected from O, N or S, and optionally substituted with 1 to 3 groups independently selected from halogen, C1- 6 alkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy; <semantics>R6<annotation encoding="application / x-tex">R_6< / annotation>< / semantics> is selected from hydrogen, halogen, hydroxyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkylhydroxy, C1-6 aminoalkyl, C3-6 cycloalkyl, C3-6 halocycloalkyl, -Y-O-C1-6 alkyl, -Y-O-C3-6 cycloalkyl, -Y-CO-NH-R13, -Y-Z, or C1-10 heterocyclyl, wherein C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylhydroxy, C1-6 aminoalkyl, C3-6 cycloalkyl, <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> halocycloalkyl or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl is optionally substituted with one or more groups selected from halogen, hydroxyl, amine, C1-6 alkoxy, C3-6 cycloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkylhydroxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> aminoalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl, wherein <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> aminoalkyl, is optionally further substituted with one or more groups selected from halogen, hydroxyl, C1-6 alkylhydroxy, <semantics>−C(O)C1−6<annotation encoding="application / x-tex">-C(O)C_{1-6}< / annotation>< / semantics> alkyl, <semantics>−C(O)NH2<annotation encoding="application / x-tex">-C(O)NH_2< / annotation>< / semantics>, <semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics> alkylhydroxy, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl; Y is selected from <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, or <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl; and <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl is optionally substituted with <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl; Z is selected from -OH, -NH2, -COOH, <semantics>−SO2NH2<annotation encoding="application / x-tex">-SO_2NH_2< / annotation>< / semantics>, <semantics>−SO2CH3<annotation encoding="application / x-tex">-SO_2CH_3< / annotation>< / semantics>, <semantics>−SOCH3<annotation encoding="application / x-tex">-SOCH_3< / annotation>< / semantics>, <semantics>−SCH3<annotation encoding="application / x-tex">-SCH_3< / annotation>< / semantics>, <semantics>−SCH3<annotation encoding="application / x-tex">-SCH_3< / annotation>< / semantics>, <semantics>−SCH3<annotation encoding="application / x-tex">-SCH_3< / annotation>< / semantics>, <semantics>−SCH3<annotation encoding="application / x-tex">-SCH_3< / annotation>< / semantics>, <semantics>−SCH3<annotation encoding="application / x-tex">-SCH_3< / annotation>< / semantics>, <semantics>−SCH3<annotation encoding="application / x-tex">-SCH_3< / annotation>< / semantics>, <semantics>−SCH3<annotation encoding="application / x-tex">-SCH_3< / annotation>< / semantics>, <semantics>−SCH3<annotation encoding="application / x-tex">-SCH_3< / annotation>< / semantics>, <semantics>−SCH3<annotation encoding="application / x-tex">-SCH_3< / annotation>< / semantics>, <semantics>−SCH3<annotation encoding="application / x-tex">-SCH_3< / annotation>< / semantics>, <semantics>−SCH3<annotation encoding="application / x-tex">-SCH_3< / annotation>< / semantics>, <semantics>−SCH3<annotation encoding="application / x-tex">-SCH_3< / annotation>< / semantics>, <semantics>−SCH3<annotation encoding="application / x-tex">-SCH_3< / annotation>< / semantics>, <semantics>−SCH3<annotation encoding="application / x-tex">-SCH_3< / annotation>< / semantics>, <semantics>−SCH3<annotation encoding="application / x-tex">-SCH_3< / annotation>< / semantics>, <semantics>−SCH3<annotation encoding="application / x-tex">-SCH_3< / annotation>< / semantics>, <semantics>−SCH3<annotation encoding="application / x-tex">-SCH_3< / annotation>< / semantics>, <semantics>−SCH3<annotation encoding="application / x-tex">-SCH_3< / annotation>< / semantics>, <semantics>−SC<annotation encoding="application / x-tex">-SC< / annotation>< / semantics> <semantics>P(=O)(OH)2<annotation encoding="application / x-tex">P(=O)(OH)_2< / annotation>< / semantics>, <semantics>−CONH2<annotation encoding="application / x-tex">-CONH_2< / annotation>< / semantics>, <semantics>−CONH(C1−6alkyl)<annotation encoding="application / x-tex">-CONH(C_{1-6} alkyl)< / annotation>< / semantics>, <semantics>−SO2NH(C1−6alkyl)<annotation encoding="application / x-tex">-SO_2NH(C_{1-6} alkyl)< / annotation>< / semantics>, <semantics>CON(C1−6alkyl)2<annotation encoding="application / x-tex">CON(C_{1-6} alkyl)_2< / annotation>< / semantics>, NHCO(<semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl), or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl, wherein <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl has 1 to 3 heteroatoms independently selected from O, N, or S, and optionally substituted with 1 to 3 groups independently selected from halogen, C1-6 alkyl, C1-6 alkoxy, or C1-6 haloalkoxy; R13 is selected from hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C1-6 alkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy, or <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> halocycloalkyl; <semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>, <semantics>R8<annotation encoding="application / x-tex">R_8< / annotation>< / semantics>, <semantics>R9<annotation encoding="application / x-tex">R_9< / annotation>< / semantics>, and <semantics>R9a<annotation encoding="application / x-tex">R_{9a}< / annotation>< / semantics> are independently selected from hydrogen, halogen, cyano, C1-6 alkyl, C3-6 cycloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy, or <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> halocycloalkyl; and n is 0, 1, or 2.

[00052] In an embodiment of the present disclosure, there is provided a compound of Formula I or its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, stereoisomers, racemates, pharmaceutically active derivatives thereof, wherein A is selected from [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] * is the point of attachment. wherein Q is N or CR1; and R1 is selected from cyano, hydrogen, halogen, C1-6 alkyl, <semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics> alkenyl, <semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics> alkynyl <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy; and <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics> alkenyl, or <semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics> alkynyl is optionally substituted with <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>alkoxy.

[00053] In an embodiment of the present disclosure, there is provided a compound of Formula I or its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, stereoisomers, racemates, pharmaceutically active derivatives thereof, wherein A is selected from [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] * is the point of attachment. Q is N or <semantics>CR1<annotation encoding="application / x-tex">CR_1< / annotation>< / semantics>; <semantics>R1<annotation encoding="application / x-tex">R_1< / annotation>< / semantics> is selected from cyano, hydrogen, halogen, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy; <semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics> is hydrogen or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl; <semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics> is hydrogen or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl; wherein <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl is optionally substituted with <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy; <semantics>R4<annotation encoding="application / x-tex">R_4< / annotation>< / semantics> and <semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics> are independently selected from hydrogen, halogen, cyano, C1-6 alkyl, C3-6 cycloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy, <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl; wherein <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl is optionally substituted with one or more groups selected from <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, <semantics>C1−<annotation encoding="application / x-tex">C_{1-}< / annotation>< / semantics> 6 alkoxy, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl, wherein <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl has 1 to 3 heteroatoms independently selected from O, N or S and optionally substituted with 1 to 3 groups independently selected from halogen, C1-6 alkyl, C1-6 alkoxy, or C1-6 haloalkoxy; R6 is selected from hydrogen, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, C1-6 alkylhydroxy, C1-6 aminoalkyl, -Y-CO-NH-R13, -Y-Z, or C1-10 heterocyclyl, wherein C1-6 alkyl, C3-6 cycloalkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 aminoalkyl, C1-6 6 alkylhydroxy, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl is optionally substituted with one or more groups selected from halogen, hydroxyl, amine, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 alkylhydroxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> aminoalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl having 1 to 4 heteroatoms independently selected from O, N or S, wherein C3-6 cycloalkyl, or C1- 6 aminoalkyl optionally substituted with 1 to 3 groups independently selected from halogen, hydroxyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkylhydroxy, - <semantics>C(O)C1−6<annotation encoding="application / x-tex">C(O)C_{1-6}< / annotation>< / semantics> alkyl, <semantics>−C(O)NH2<annotation encoding="application / x-tex">-C(O)NH_2< / annotation>< / semantics>, <semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics> alkylhydroxy, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl; Y is <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> 6 alkyl or <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, wherein <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl optionally substituted with <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl; Z is selected from -OH, -NH2, -COOH, -SO2NH2, -SO2CH3, - <semantics>S(=O)CH3<annotation encoding="application / x-tex">S(=O)CH_3< / annotation>< / semantics>, <semantics>−SCH3<annotation encoding="application / x-tex">-SCH_3< / annotation>< / semantics>, <semantics>CH2<annotation encoding="application / x-tex">CH_2< / annotation>< / semantics>-NH-<semantics>(C1−6<annotation encoding="application / x-tex">(C_{1-6}< / annotation>< / semantics> alkyl)-<semantics>SOCH3<annotation encoding="application / x-tex">SOCH_3< / annotation>< / semantics>, <semantics>−O<annotation encoding="application / x-tex">-O< / annotation>< / semantics>-<semantics>P(=O)(OH)2<annotation encoding="application / x-tex">P(=O)(OH)_2< / annotation>< / semantics>, <semantics>CONH2<annotation encoding="application / x-tex">CONH_2< / annotation>< / semantics>, <semantics>CON(C1−6 alkyl)2−CONH(C1−6 alkyl),−SO2NH(C1−6 alkyl), or -NHCO(C1−6 alkyl);<annotation encoding="application / x-tex">CON(C_{1-6} \text{ alkyl})_2 - CONH(C_{1-6} \text{ alkyl}), -SO_2NH(C_{1-6} \text{ alkyl}), \text{ or -NHCO}(C_{1-6} \text{ alkyl});< / annotation>< / semantics> <semantics>R13<annotation encoding="application / x-tex">R_{13}< / annotation>< / semantics> is selected from hydrogen, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy, or <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> halocycloalkyl; <semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>, <semantics>R8<annotation encoding="application / x-tex">R_8< / annotation>< / semantics>, <semantics>R9<annotation encoding="application / x-tex">R_9< / annotation>< / semantics>, and <semantics>R9a<annotation encoding="application / x-tex">R_{9a}< / annotation>< / semantics> are independently selected from hydrogen, halogen, cyano, C1-6 alkyl, C3-6 cycloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy, or <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> halocycloalkyl; and n is 0, 1 or 2.

[00054] In an embodiment of the present disclosure, there is provided a compound of Formula 1 or its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, stereoisomers, racemates, pharmaceutically active derivatives thereof, wherein A is selected from [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] * is the point of attachment, wherein Q is N or CR1; R1 is selected from cyano, hydrogen, halogen, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy; <semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics> is hydrogen or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl; <semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics> is hydrogen or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl and wherein <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl is optionally substituted with <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy; <semantics>R4<annotation encoding="application / x-tex">R_4< / annotation>< / semantics> and <semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics> are independently selected from hydrogen, halogen, cyano, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy, -CO-N(<semantics>R10<annotation encoding="application / x-tex">R_{10}< / annotation>< / semantics> <semantics>R11<annotation encoding="application / x-tex">R_{11}< / annotation>< / semantics>), <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl, wherein <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl optionally substituted with one or more groups selected from <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl, wherein the <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl has 1 to 4 heteroatoms independently selected from O, N or S and optionally substituted with 1 to 3 groups independently selected from halogen, C1-6 alkyl, C1-6 alkoxy, or C1-6 haloalkoxy; <semantics>R10<annotation encoding="application / x-tex">R_{10}< / annotation>< / semantics> is hydrogen or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl; <semantics>R11<annotation encoding="application / x-tex">R_{11}< / annotation>< / semantics> is selected from hydrogen, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl, wherein <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl is optionally substituted with one or more groups selected from halogen, <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl; <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl has 1 to 4 heteroatoms independently selected from O, N or S, and optionally substituted with 1 to 3 groups independently selected from halogen, C1-6 alkyl, C1-1 6 alkoxy, C1-6 haloalkoxy, *-- *-- *-- *-- *-- *-- *-- *-- *-- *-- [Image disponible dans le document PDF, Image available in the PDF document] R6 is selected from hydrogen, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkylhydroxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> aminoalkyl, -Y-CO-NH-<semantics>R13<annotation encoding="application / x-tex">R_{13}< / annotation>< / semantics>, -Y-Z, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl, wherein C1-6 alkyl, C3-6 cycloalkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 aminoalkyl, C1-6 6 alkylhydroxy, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl is optionally substituted with one or more groups selected from halogen, hydroxyl, amine, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 alkylhydroxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> aminoalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy, <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl having 1 to 4 heteroatoms independently selected from O, N or S; wherein C3-6 cycloalkyl, or C1- 6 aminoalkyl is optionally further substituted with one or more groups selected from halogen, hydroxyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkylhydroxy, - <semantics>C(O)C1−6<annotation encoding="application / x-tex">C(O)C_{1-6}< / annotation>< / semantics> alkyl, <semantics>−C(O)NH2<annotation encoding="application / x-tex">-C(O)NH_2< / annotation>< / semantics>, <semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics> alkylhydroxy, <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl, cyclopropyl, cyclobutyl, CH2CF3, CH2CHFCH3, CH2CF2CH3, CH2C(CH3)2OH, C(CH3)2OH, C(CD3)2OH, CH2OH, CH2OCH3, CH2OCF3, C(CH3CF3)OH, CH2CH2OH, CH2CH2OCH3, CH2CH(OCH3)CH3, C(CH3)2NH2, CH2NH2, <semantics>CH2CH2NH2<annotation encoding="application / x-tex">CH_2CH_2NH_2< / annotation>< / semantics>, <semantics>CH2CH2NHCH3<annotation encoding="application / x-tex">CH_2CH_2NHCH_3< / annotation>< / semantics>, <semantics>CH2CH(NH2)CH3<annotation encoding="application / x-tex">CH_2CH(NH_2)CH_3< / annotation>< / semantics>, <semantics>CH2CH2N(CH3)2<annotation encoding="application / x-tex">CH_2CH_2N(CH_3)_2< / annotation>< / semantics>, CH2CHFCH2NH2, OCH3, OCF3, OCH2CF3, OCH2CH2OCH3, OCH2CH2OCHCF2, OCH2CH2OH, OCH2CH2OCF3, CH2CF2CH2OH, <semantics>CH2C(CH3)2CH2OH<annotation encoding="application / x-tex">CH_2C(CH_3)_2CH_2OH< / annotation>< / semantics>, CHCF3OH, CHOHCH2OH, CHOHCH2OCH3, CH2CH2CH2OH, CH2CH2NHCH2CH2OH, CH2NHCH2CH2OH,CH2CH2NHCOCH3, <semantics>CH2CH2S(=O)CH3<annotation encoding="application / x-tex">CH_2CH_2S(=O)CH_3< / annotation>< / semantics>, <semantics>CH2CH2CH2S(=O)CH3<annotation encoding="application / x-tex">CH_2CH_2CH_2S(=O)CH_3< / annotation>< / semantics>, [Image disponible dans le document PDF, Image available in the PDF document] ; Y is <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl or <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, wherein <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl optionally substituted with C3-6 cycloalkyl; Z is selected from -OH, -NH2, -COOH, -SO2NH2, -SO2CH3, - <semantics>S(=O)CH3<annotation encoding="application / x-tex">S(=O)CH_3< / annotation>< / semantics>, <semantics>−SCH3<annotation encoding="application / x-tex">-SCH_3< / annotation>< / semantics>, <semantics>CH2<annotation encoding="application / x-tex">CH_2< / annotation>< / semantics>-NH-<semantics>(C1−6<annotation encoding="application / x-tex">(C_{1-6}< / annotation>< / semantics> alkyl)-SOCH3, <semantics>−O<annotation encoding="application / x-tex">-O< / annotation>< / semantics>-P<semantics>(=O)(OH)2<annotation encoding="application / x-tex">(=O)(OH)_2< / annotation>< / semantics>, <semantics>CONH2<annotation encoding="application / x-tex">CONH_2< / annotation>< / semantics>, <semantics>CON(C1−6 alkyl)2−CONH(C1−6 alkyl),−SO2NH(C1−6 alkyl), or -NHCO(C1−6 alkyl);<annotation encoding="application / x-tex">CON(C_{1-6} \text{ alkyl})_2 - CONH(C_{1-6} \text{ alkyl}), -SO_2NH(C_{1-6} \text{ alkyl}), \text{ or -NHCO}(C_{1-6} \text{ alkyl});< / annotation>< / semantics> and R13 is selected from hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy, or <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> halocycloalkyl; <semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>, <semantics>R8<annotation encoding="application / x-tex">R_8< / annotation>< / semantics>, <semantics>R9<annotation encoding="application / x-tex">R_9< / annotation>< / semantics>, and <semantics>R9a<annotation encoding="application / x-tex">R_{9a}< / annotation>< / semantics> are independently selected from hydrogen, halogen, cyano, C1-6 alkyl, C3-6 cycloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy, or <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> halocycloalkyl; and n is 0, 1 or 2.

[00055] In an embodiment of the present disclosure, there is provided a compound of Formula I or its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, stereoisomers, racemates, pharmaceutically active derivatives thereof, wherein A is selected from [Image disponible dans le document PDF, Image available in the PDF document] -- [Image disponible dans le document PDF, Image available in the PDF document] Q is N or CR1; R1 is selected from cyano, hydrogen, halogen, C1-6 alkyl, or C1-6 alkoxy; <semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics> is hydrogen or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl; <semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics> is hydrogen or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl; <semantics>R4<annotation encoding="application / x-tex">R_4< / annotation>< / semantics> and <semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics> are independently selected from hydrogen, halogen, cyano, C1-6 alkyl, C3-6 cycloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy; wherein <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl optionally substituted with one or more groups selected from <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy; R6 is selected from hydrogen, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkylhydroxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> aminoalkyl, -Y-CO-NH-<semantics>R13<annotation encoding="application / x-tex">R_{13}< / annotation>< / semantics>, -Y-Z, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl, wherein C1-6 alkyl, C3-6 cycloalkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 aminoalkyl, C1-6 6 alkylhydroxy, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl is optionally substituted with one or more groups independently selected from halogen, hydroxyl, C3-6 cycloalkyl, C1-6 alkoxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkylhydroxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> aminoalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkoxy, <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl, wherein <semantics>C3−1<annotation encoding="application / x-tex">C_{3-1}< / annotation>< / semantics> 6 cycloalkyl, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> aminoalkyl is optionally further substituted with one or more groups independently selected from halogen, hydroxyl, C1-6 alkylhydroxy, - <semantics>C(O)C1−6<annotation encoding="application / x-tex">C(O)C_{1-6}< / annotation>< / semantics> alkyl, <semantics>−C(O)NH2<annotation encoding="application / x-tex">-C(O)NH_2< / annotation>< / semantics>, or <semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics> alkylhydroxy; Y is <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl or <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl; Z is selected from -OH, -NH2, -COOH, -SO2NH2, -SO2CH3, -SOCH3, - SCH3, CH2-NH-(C1-6 alkyl)-SOCH3, -CONH2, -CONH(C1-6 alkyl), -SO2NH(C1-6 alkyl), <semantics>CON(C1−6 alkyl)2<annotation encoding="application / x-tex">CON(C_{1-6} \text{ alkyl})_2< / annotation>< / semantics>, or -NHCO(<semantics>C1−6 alkyl<annotation encoding="application / x-tex">C_{1-6} \text{ alkyl}< / annotation>< / semantics>); <semantics>R13<annotation encoding="application / x-tex">R_{13}< / annotation>< / semantics> is selected from hydrogen, <semantics>C1−6 alkyl<annotation encoding="application / x-tex">C_{1-6} \text{ alkyl}< / annotation>< / semantics> 6 alkyl, or C3-6 cycloalkyl; R7, R8, R9, and R9a are independently selected from hydrogen, halogen, cyano, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy; and n is 0, 1, or 2.

[00056] In an embodiment of the present disclosure, there is provided a compound of Formula I or its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, stereoisomers, racemates, pharmaceutically active derivatives thereof, wherein A is selected from [Image disponible dans le document PDF, Image available in the PDF document] Q is N; <semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics> is hydrogen or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl; <semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics> is hydrogen or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl; <semantics>R4<annotation encoding="application / x-tex">R_4< / annotation>< / semantics> and <semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics> are independently selected from halogen, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl; wherein <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl is optionally substituted with <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl; <semantics>R6<annotation encoding="application / x-tex">R_6< / annotation>< / semantics> is selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 alkylhydroxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> aminoalkyl, -Y-CO-NH-<semantics>R13<annotation encoding="application / x-tex">R_{13}< / annotation>< / semantics>, -Y-Z, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl, wherein <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> haloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> aminoalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkylhydroxy, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl is optionally substituted with one or more groups selected from halogen, hydroxyl, amine, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy, <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkylhydroxy, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> aminoalkyl, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl; wherein <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> aminoalkyl, is optionally further substituted with one or more groups independently selected from halogen, hydroxyl, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkylhydroxy, <semantics>−C(O)C1−6<annotation encoding="application / x-tex">-C(O)C_{1-6}< / annotation>< / semantics> alkyl, <semantics>−C(O)NH2<annotation encoding="application / x-tex">-C(O)NH_2< / annotation>< / semantics>, or <semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics> 6alkylhydroxy; Y is C1-6 alkyl, or C3-6 cycloalkyl; Z is selected from -SOCH3, -SCH3, CH2-NH-(C1-6 alkyl)-SOCH3, or -NHCO(C1-6 alkyl); R13 is selected from hydrogen, C1-6 alkyl, or C3-6 cycloalkyl; R7, R8, R9, and <semantics>R9a<annotation encoding="application / x-tex">R_{9a}< / annotation>< / semantics> are independently selected from hydrogen, halogen, cyano, <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl or <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkoxy; and n is 0, or 1.

[00057] In an embodiment of the present disclosure, there is provided a compound of Formula I or its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, stereoisomers, racemates, pharmaceutically active derivatives thereof, is selected from a group consisting of: 1.7-amino-2,3-dimethyl-5-{[1-(6-methylpyridin-2- yl)ethyl]amino}pyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 2. 7-amino-2,3-dimethyl-5-{[(1S)-1-(6-methylpyridin-2- yl)ethyl]amino}pyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 3. (R)-7-Amino-3-ethyl-2-methyl-5-((1-(pyridin-2-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 4. (S)-7-Amino-3-ethyl-2-methyl-5-((1-(pyridin-2-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 5. (S)-7-Amino-3-ethyl-2-methyl-5-((1-(6-methylpyridin-2-yl) ethyl) amino) pyrazolo [1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 6. 7-amino-2,3-dimethyl-5-{[(6-methylpyridin-2- yl)methyl]amino}pyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 7. 7-amino-5-{[(6-ethylpyridin-2-yl)methyl]amino}-2,3- dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 8. 7-amino-2,3-dimethyl-5-{methyl[(6-methylpyridin-2- yl)methyl]amino}pyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 9. 7-amino-5-({[6-(2-hydroxypropan-2-yl)pyridin-2- yl]methyl}amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 10. 7-Amino-2,3-dimethyl-5-((2-(5-methylpyridin-2-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 11. 7-amino-5-((2-(5-fluoropyridin-2-yl)ethyl)amino)-2,3- dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 12. 7-amino-5-((2-(6-methoxypyridin-2-yl)ethyl)amino)-2,3- dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] - 13. 7-amino-5-((2-(6-methylpyridin-2-yl)ethyl)amino)-2,3- dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] - 14. Chiral 7-amino-2,3-dimethyl-5-{[1-(6-methylpyridin-2-yl)propan- 2-yl]amino}pyrazolo[1,5-a]pyrimidine-6-carbonitrile (Isomer 1); [Image disponible dans le document PDF, Image available in the PDF document] 15. Chiral 7-amino-2,3-dimethyl-5-{[1-(6-methylpyridin-2-yl)propan- 2-yl]amino}pyrazolo[1,5-a]pyrimidine-6-carbonitrile (Isomer2); [Image disponible dans le document PDF, Image available in the PDF document] 16. 7-amino-5-({2-[6-(2-hydroxypropan-2-yl)pyridin-2- yl]ethyl}amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 17. 7-Amino-3-ethyl-2-methyl-5-((2-(6-methylpyridin-2-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 18. 7-Amino-3-ethyl-2-methyl-5-((2-(5-methylpyridin-2-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 19. 7-Amino-3-ethyl-5-((2-(5-methoxypyridin-2-yl) ethyl) amino)-2- methylpyrazolo [1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 20. 7-Amino-3-ethyl-5-((2-(6-methoxypyridin-2-yl) ethyl) amino)-2- methylpyrazolo [1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 21. 7-Amino-3-ethyl-5-((2-(5-fluoropyridin-2-yl) ethyl) amino)-2- methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 22. Chiral 7-Amino-3-ethyl-2-methyl-5-((1-(pyridin-2-yl) propan-2-yl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile (isomer 1); [Image disponible dans le document PDF, Image available in the PDF document] 23. Chiral 7-Amino-3-ethyl-2-methyl-5-((1-(pyridin-2-yl) propan-2-yl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile( isomer 2); [Image disponible dans le document PDF, Image available in the PDF document] 24. 7-Amino-3-ethyl-2-methyl-5-((1-(6-methylpyridin-2-yl) propan-2- yl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 25. 7-amino-3-ethyl-5-({2-[6-(2-hydroxypropan-2-yl)pyridin-2- yl]ethyl}amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 26. 7-amino-3-(cyclopropylmethyl)-2-methyl-5-((2-(6-methylpyridin- 2-yl)ethyl) amino) pyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 27. 7-amino-3-(isopropylmethyl)-2-methyl-5-((2-(6-methylpyridin-2- yl)ethyl) amino) pyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 28. 7-amino-3-(isopropyl)-2-methyl-5-((2-(6-methylpyridin-2-yl)ethyl) amino) pyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 29. [Image disponible dans le document PDF, Image available in the PDF document] dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] • 30. 7-amino-3-ethyl-5-{[2-(1-ethyl-1H-pyrazol-3-yl)ethyl]amino}-2- methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 31. 7-amino-5-({2-[1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazol-3- yl]ethyl}amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 32. 7-amino-3-ethyl-5-((2-(1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazol-3- yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 33. 7-amino-3-chloro-5-((2-(6-(hydroxymethyl) pyridin-2-yl) ethyl) amino)-2- methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 34. 7-amino-3-chloro-5-((2-(6-(1-(hydroxymethyl) cyclopropyl) pyridin-2-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 35. 7-amino-3-chloro-5-((2-(1-(2-hydroxyethyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 36. 7-amino-3-chloro-5-((2-(1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazol- 3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] · · · · · · · · · · · · · · · · · · · 37. 7-amino-3-chloro-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-1H-pyrazol- 3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 38. 7-amino-3-chloro-5-((2-(6-(2-(hydroxymethyl) cyclopropyl) pyridin-2-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 39. 7-amino-3-ethyl-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-1H-pyrazol-3- yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile. [Image disponible dans le document PDF, Image available in the PDF document] 40. amino-5-((2-(6-ethylpyridin-2-yl) ethyl) amino)-2,3-dimethylpyrazolo [1,5-a] pyrimidine -6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 41. 7-amino-5-((2-(3-fluoro-6-methylpyridin-2-yl) ethyl) amino)-2,3- dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 42. 7-amino-2-ethyl-3-methyl-5-((2-(6-methylpyridin-2-yl) ethyl) amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 43. 7-amino-2-ethyl-5-((2-(6-(2-hydroxypropan-2-yl) pyridin-2- yl)ethyl)amino)-3-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 44. 7-amino-5-((2-(6-(hydroxymethyl) pyridin-2-yl) ethyl) amino)-2,3- dimethylpyrazolo [1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 45. 7-amino-3-ethyl-5-((2-(6-(hydroxymethyl) pyridin-2-yl) ethyl)amino)-2- methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 46. 7-amino-3-(cyclopropyl methyl)-5-((2-(6-(hydroxymethyl) pyridin-2-yl) ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 47. 7-amino-2-cyclopropyl-5-((2-(6-(2-hydroxypropan-2-yl) pyridin-2-yl) ethyl)amino)-3-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 48. 7-amino-2-(difluoromethyl)-3-ethyl-5-((2-(1-(1-hydroxy-2-methylpropan- 2-yl)-1H-pyrazol-3-yl) ethyl) amino)pyrazolo[1,5-a]pyrimidine-6- carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 49. 7-amino-5-((2-(6-(1-(hydroxymethyl) cyclopropyl) pyridin-2-yl) ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 50. 7-amino-3-ethyl-5-((2-(6-(1-(hydroxymethyl) cyclopropyl) pyridin-2-yl) ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 51. 7-amino-5-((2-(6-(2-(hydroxymethyl) cyclopropyl) pyridin-2-yl) ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 52. 7-amino-3-ethyl-5-((2-(6-(1-hydroxy-2-methylpropan-2-yl) pyridin-2-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 53. 7-amino-5-((2-(6-(1-hydroxy-2-methylpropan-2-yl) pyridin-2-yl) ethyl) amino)-2,3-dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 54. 7-amino-3-ethyl-5-((2-(1-(2-hydroxyethyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 55. 7-amino-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino)-2,3-dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 56. 7-amino-2-(difluoro methyl)-3-ethyl-5-((2-(6-(hydroxymethyl) pyridin-2- yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 57. 7-amino-5-(((1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazol-3-yl) methyl) amino)-2,3-dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 58. 7-amino-2-(difluoro <semantics>methyl<annotation encoding="application / x-tex">methyl< / annotation>< / semantics>)-3-ethyl-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6- carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 59. 7-amino-2-(difluoro <semantics>methyl<annotation encoding="application / x-tex">methyl< / annotation>< / semantics>)-3-ethyl-5-((2-(6-(2-(hydroxymethyl) cyclopropyl) pyridin-2-yl) ethyl) amino) pyrazolo[1,5-a]pyrimidine-6- carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 60. 7-amino-3-ethyl-5-((2-(6-(2-(hydroxymethyl) cyclopropyl) pyridin-2-yl) ethyl) amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 61. 7-amino-3-chloro-5-((2-(4-(1-(hydroxymethyl) cyclopropyl) thiazol-2- yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 62. 7-amino-3-ethyl-5-((2-(4-fluoro-1-(1-hydroxy-2-methylpropan-2-yl)- 1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6- carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 63. 7-amino-3-ethyl-5-((2-(1-((1-(hydroxymethyl) cyclopropyl) methyl)- 1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6- carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 64. 7-amino-3-chloro-5-((2-(6-(1,1-difluoro-2-hydroxyethyl) pyridin-2-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 65. 7-amino-3-chloro-5-((2-(6-(1-hydroxy-2-methylpropan-2-yl) pyridin- 2-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 66. 7-amino-3-ethyl-5-((2-(4-(1-(hydroxymethyl) cyclopropyl) thiazol-2- yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 67. 7-amino-3-chloro-5-((2-(1-(2-(hydroxymethyl) cyclobutyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 68. 7-amino-5-((2-(1-(1-(amino methyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino)-3-chloro-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 69. 7-amino-3-bromo-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 70. 7-amino-3-chloro-5-((2-(1-ethyl-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)-2- methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 71. 7-amino-3-ethyl-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] - 72. 7-amino-3-bromo-5-((2-(6-(hydroxymethyl) pyridine-2-yl) ethyl) amino)-2- methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 73. 7-amino-3-chloro-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-1H-pyrazol-4-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 74. 7-amino-3-(cyclopropyl methyl)-5-((2-(1-(1-(hydroxymethyl) cyclopropyl) -1H- pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 75. 7-amino-3-chloro-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-5-methyl-1H- pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 76. 7-amino-3-ethyl-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-5-methyl-1H- pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 77. N-((1-(3-(2-((7-amino-3-chloro-6-cyano-2-methylpyrazolo[1,5-a] pyrimidin-5-yl) amino) ethyl)-1H-pyrazol-1-yl) cyclopropyl) methyl) acetamide; [Image disponible dans le document PDF, Image available in the PDF document] 78. (+)- 7-amino-3-ethyl-5-((2-(1-(2-(hydroxymethyl)cyclobutyl)-1H-pyrazol-3- yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] Example 78; dextro(+) rotatory 79. (-) - 7-amino -3-ethyl-5-((2-(1-(2-(hydroxymethyl)cyclobutyl)-1H-pyrazol-3- yl)ethyl) amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] Example 79; leavo(-) rotatory 80. 7-amino-3-ethyl-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-5-methyl-1H-pyrazol- 3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 81. 7-amino-3-ethyl-5-((2-(1-(1-hydroxypropan-2-yl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 82. (+-) - 7-amino-3-chloro-5-((2-(1-((3-hydroxycyclobutyl) methyl)-1H-pyrazol-3- yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 83. (+) - 7-amino-3-chloro-5-((2-(1-((3-hydroxycyclobutyl) methyl)-1H-pyrazol-3- yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 84. (-) - 7-amino-3-chloro-5-((2-(1-((3-hydroxycyclobutyl) methyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile(83b); [Image disponible dans le document PDF, Image available in the PDF document] 85. 7-amino-3-ethyl-5-((2-(1-((3-hydroxycyclobutyl) methyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 86. 7-amino-5-((2-(1-(1-(hydroxy methyl) cyclopropyl)-5-methyl-1H-pyrazol-3-yl) ethyl) amino)-2,3-dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 87. 7-amino-3-chloro-2-methyl-5-((2-(1-methyl-2-oxo-1,2-dihydropyridin 3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 88. 7-amino-3-ethyl-2-methyl-5-((2-(1-methyl-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 89. 7-amino-3-bromo-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-5-methyl-1H- pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 90. 7-amino-3-chloro-5-((2-(6-(((2-hydroxyethyl) amino) methyl) pyridin-2-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 91. 7-amino-3-ethyl-5-((2-(5-fluoro-6-(hydroxymethyl)46yridine-2-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 92. 7-amino-3-chloro-5-((2-(1-(2-methoxyethyl)-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 93. 7-amino-3-chloro-5-((2-(1-(2-hydroxyethyl)-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 94. 7-amino-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methyl-3-(trifluoromethyl) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 95. 7-amino-5-((2-(1-(2-(amino methyl) cyclobutyl)-1H-pyrazol-3-yl) ethyl) amino)-3-chloro-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 96. 7-amino-3-ethyl-5-((2-(6-(((2-methoxyethyl) amino) methyl)47yridine-2-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 97. 7-amino-3-ethyl-5-((2-(6-(((2-hydroxyethyl) amino) methyl) pyridine-2-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 98. 7-amino-3-chloro-5-((2-(1-(1-(((2-hydroxyethyl) amino) methyl) cyclopropyl)- 1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6- carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 99. N-((1-(3-(2-((7-amino-3-chloro-6-cyano-2-methylpyrazolo[1,5-a] pyrimidin- 5-yl) amino) ethyl)-1H-pyrazol-1-yl) cyclopropyl) methyl)-3- hydroxypropanamide; [Image disponible dans le document PDF, Image available in the PDF document] 100. 7-amino-3-ethyl-5-((2-(6-(1-hydroxyethyl)49yridine-2-yl) ethyl) amino)-2- methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 101. 7-amino-3-cyclopropyl-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-1H- pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 102. 7-amino-2-(difluoro <semantics>methyl<annotation encoding="application / x-tex">methyl< / annotation>< / semantics>)-3-ethyl-5-((2-(1-(2-(hydroxymethyl) cyclobutyl)-1H-pyrazol-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6- carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 103: 104a, and 104b. (+-)-7-amino-5-((2-(1-(2-(hydroxymethyl) cyclobutyl)-1H- pyrazol-3-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile (103), (+)-7-amino-5-((2-(1-(2-(hydroxymethyl) cyclobutyl) -1H-pyrazol-3- yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile(104a), (-)- 7-amino-5-((2-(1-(2-(hydroxymethyl)cyclobutyl)-1H-pyrazol-3-yl)ethyl)amino)- 2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile(104b); [Image disponible dans le document PDF, Image available in the PDF document] Example 103; racemic(+) Example 104a; Peak 1;dextro(+) rotatory Example 104b; Peak 2; leavo(-) rotatory 105. 7-amino-5-((2-(6-(((2-hydroxyethyl) amino) methyl) pyridin-2-yl) ethyl) amino)-2,3-dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 106. 7-amino-3-ethyl-5-((2-(1-(1-(((2-hydroxyethyl) amino) methyl) cyclopropyl)- 1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6- carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 107. 7-amino-3-ethyl-5-((2-(1-(2-methoxyethyl)-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 108. 7-amino-3-ethyl-5-((2-(1-(2-hydroxyethyl)-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 109. 7-amino-5-((2-(1-(2-(amino methyl) cyclobutyl)-1H-pyrazol-3-yl) ethyl) amino)-3-ethyl-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] _ 110. 7-amino-3-ethyl-5-((2-(1-(3-hydroxypropyl)-1H-pyrazol-5-yl) ethyl) amino)- 2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 111. 7-amino-3-ethyl-5-((2-(1-(3-hydroxypropyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 112. 7-amino-3-chloro-5-((2-(1-(1-(2-hydroxyethyl) cyclopropyl)-1H-pyrazol-3- yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 113. 7-amino-3-ethyl-5-((2-(1-(3-hydroxypropyl)-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 114. 7-amino-3-chloro-5-((2-(1-(2-(hydroxymethyl) cyclopentyl)-1H-pyrazol-3- yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 115. 7-amino-3-ethyl-5-((2-(1-(2-(hydroxymethyl) cyclopentyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 116. 7-amino-3-(cyclopropyl methyl)-5-((2-(1-(2-(hydroxymethyl) cyclobutyl)- 1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6- carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 117. 7-amino-3-chloro-5-((2-(1-(2-(((2-hydroxyethyl) amino) methyl) cyclobutyl)- 1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6- carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 118. 7-amino-5-((2-(1-(2-(amino methyl) cyclopentyl)-1H-pyrazol-3-yl) ethyl) amino)-3-chloro-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 119. 7-amino-3-chloro-2-methyl-5-((2-(6-methylpyridin-2-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 120. 7-amino-3-chloro-5-((2-(6-ethylpyridin-2-yl) ethyl) amino)-2- methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 121. (+-)-7-amino-3-cthyl-5-((2-(1-(4-(hydroxymethyl)tetrahydrofuran-3-yl)-1H- pyrazol-3-yl)ethyl)amino)-2-methyl pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 122a. (+)-7-amino-3-ethyl-5-((2-(1-(4-(hydroxy methyl)tetrahydrofuran-3-yl)- 1H-pyrazol-3-yl)ethyl)amino)-2-methyl pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 122b. (-)-7-amino-3-cthyl-5-((2-(1-(4-(hydroxy methyl)tetrahydrofuran-3-yl)-1H- pyrazol-3-yl)ethyl)amino)-2-methyl pyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] Example 121; racemic(+) Example 122a; Peak 1;dextro(+) rotatory Example 122b; Peak 2; leavo(-) rotatory 123. 7-amino-3-ethyl-5-((2-(1-(3-(hydroxymethyl) cyclobutyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 124. 7-amino-3-ethyl-5-((2-(1-(1-(2-hydroxyethyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 125. 7-amino-5-((2-(1-(2-aminoethyl)-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)-3-chloro-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 126. 7-amino-5-((2-(1-(2-aminoethyl)-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)-3-ethyl-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 127. 7-amino-3-chloro-5-((2-(1-(4-(hydroxymethyl) tetrahydrofuran-3-yl)-1H- pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 128. 7-amino-3-ethyl-5-((2-(1-((3-hydroxycyclobutyl) methyl)-2-oxo-1,2- dihydropyridin-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a]pyrimidine-6- carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 129. 7-amino-5-((2-(1-(3-aminopropyl)-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)-3-chloro-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 130. 7-amino-3-bromo-5-((2-(1-(2-(hydroxymethyl) cyclobutyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 131. 7-amino-2-(difluoromethyl)-3-ethyl-5-((2-(1-(2-hydroxyethyl)-2-oxo-1,2- dihydropyridin-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 132. (+-)-7-amino-5-((2-(1-(4-(hydroxymethyl) tetrahydrofuran-3-yl)-1H-pyrazol- 3-yl) ethyl) amino)-2,3-dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; 133a. (+)-7-amino-5-((2-(1-(4-(hydroxymethyl) tetrahydrofuran-3-yl)-1H- pyrazol-3-yl) ethyl) amino)-2,3-dimethylpyrazolo[1,5-a] pyrimidine-6- carbonitrile; 133b. (-)-7-amino-5-((2-(1-(4-(hydroxymethyl) tetrahydrofuran-3-yl)-1H-pyrazol- 3-yl) ethyl) amino)-2,3-dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] Example 132; racemic(+) Example 133a; Peak 1;dextro(+) rotatory Example 133b; Peak 2; leavo(-) rotatory 134. 2-(((2-(3-(2-((7-amino-6-cyano-3-ethyl-2-methylpyrazolo[1,5-a] pyrimidin- 5-yl) amino) ethyl)-1H-pyrazol-1-yl) cyclobutyl) methyl) amino) acetamide; [Image disponible dans le document PDF, Image available in the PDF document] 135. 7-amino-3-ethyl-2-methyl-5-((2-(6-(2,2,2-trifluoro-1-hydroxyethyl) pyridine- 2-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6 carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 136. 7-amino-5-((2-(1-(3-aminopropyl)-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)-3-ethyl-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 137. 7-amino-3-(cyclo butyl methyl)-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)- 1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6- carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 138. 7-amino-5-((2-(1-(3-hydroxypropyl)-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)-2,3-dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 139. 7-amino-3-ethyl-5-((2-(6-(2-hydroxyethyl) pyridine-2-yl) ethyl) amino)-2- methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 140. 7-amino-2,3-dimethyl-5-((2-(6-methylpyrazin-2-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 141. 7-amino-5-((2-(1-(3-aminopropyl)-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)-2,3-dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 142. 7-amino-3-ethyl-2-methyl-5-((2-(1-(2-(methylthio) ethyl)-2-oxo-1,2- dihydropyridin-3-yl) ethyl) amino) pyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 143. Racemic (+-)7-amino-3-ethyl-2-methyl-5-((2-(1-(2-(methyl sulfinyl) ethyl)-2- oxo-1,2-dihydropyridin-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6- carbonitrile; 144a. (+)7-amino-3-ethyl-2-methyl-5-((2-(1-(2-(methyl sulfinyl) ethyl)-2-oxo-1,2- dihydropyridin-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; 144b. (-)7-amino-3-ethyl-2-methyl-5-((2-(1-(2-(methyl sulfinyl) ethyl)-2-oxo-1,2- dihydropyridin-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 145. N-(3-(3-(2-((7-amino-6-cyano-3-ethyl-2-methylpyrazolo[1,5-a] pyrimidin-5- yl) amino) ethyl)-2-oxopyridin-1(2H)-yl) propyl) acetamide; [Image disponible dans le document PDF, Image available in the PDF document] 146. 7-amino-5-((2-(1-(1-(amino methyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino)-3-ethyl-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 147. N-((1-(3-(2-((7-amino-6-cyano-3-ethyl-2-methylpyrazolo[1,5-a] pyrimidin- 5-yl) amino) ethyl)-1H-pyrazol-1-yl) cyclopropyl) methyl) acetamide; [Image disponible dans le document PDF, Image available in the PDF document] 148. 7-amino-5-((2-(1-(1-(2-aminoethyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino)-3-ethyl-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 149. N-(2-(1-(3-(2-((7-amino-6-cyano-3-ethyl-2-methylpyrazolo[1,5-a] pyrimidin-5-yl) amino) ethyl)-1H-pyrazol-1-yl) cyclopropyl) ethyl) acetamide; [Image disponible dans le document PDF, Image available in the PDF document] 150: 7-amino-3-ethyl-5-((2-(6-(2-hydroxyethoxy)61yridine-2-yl) ethyl) amino)-2- methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 151. 7-amino-5-((2-(1-(1-(2-aminoethyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino)-3-chloro-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 152. 7-amino-5-((2-(6-(2-hydroxyethyl)61yridine-2-yl) ethyl) amino)-2,3- dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 153. 7-amino-3-ethyl-2-methyl-5-((2-(1-(3-(methylthio) propyl)-2-oxo-1,2- dihydropyridin-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 154a (-)-7-amino-3-ethyl-2-methyl-5-((2-(1-(3-(methyl sulfinyl) propyl)-2-oxo- 1,2-dihydropyridin-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; 154b. (+)-7-amino-3-ethyl-2-methyl-5-((2-(1-(3-(methyl sulfinyl) propyl)-2-oxo- 1,2-dihydropyridin-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] Example 154a; Peak 1; leavo (-) rotatory Example 154b; Peak 2; dextro (+) rotatory 155. 7-amino-3-ethyl-5-((2-(6-(3-hydroxypropyl) pyridin-2-yl) ethyl) amino)-2- methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 156. 7-amino-5-((2-(1-(3-hydroxypropyl)-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)-2-methyl-3-propylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 157. 7-amino-5-((2-(6-(hydroxymethyl)63yridine-2-yl) ethyl) amino)-2-methyl-3- propylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 158. 7-amino-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methyl-3-propylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 159a. (+)-7-amino-3-ethyl-5-((2-(6-(1-hydroxyethyl) pyridin-2-yl) ethyl) amino)- 2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; 159b.(-)-7-amino-3-ethyl-5-((2-(6-(1-hydroxyethyl) pyridine-2-yl) ethyl) amino)- 2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] Example 159a Peak1: dextro(+) rotatory Example 159b Peak1: leavo(-) rotatory 160a. (+) 7-amino-5-((2-(1-(4-(hydroxymethyl) tetrahydrofuran-3-yl)-1H-pyrazol- 3-yl) ethyl) amino)-2-methyl-3-propylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; 160b. (-) 7-amino-5-((2-(1-(4-(hydroxymethyl) tetrahydrofuran-3-yl)-1H-pyrazol- 3-yl) ethyl) amino)-2-methyl-3-propylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] Example 160a; Peak1; Dextro(+) rotatory Example 160b; Peak2; leavo (-) rotatory 161. 7-amino-3-ethyl-2-methyl-5-((2-(1-(3-(methylthio) propyl)-1H-pyrazol-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 162a (-)-7-amino-3-ethyl-2-methyl-5-((2-(1-(3-(methyl sulfinyl) propyl)-1H- pyrazol-3-yl) ethyl) amino) pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 162b. <semantics>(+)<annotation encoding="application / x-tex">(+)< / annotation>< / semantics>-7-amino-3-ethyl-2-methyl-5-<semantics>((2−(1−(3−(methylsulfinyl)propyl)−1H−<annotation encoding="application / x-tex">((2-(1-(3-(methylsulfinyl)propyl)-1H-< / annotation>< / semantics> pyrazol-3-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] Peak 1; Example 162a; leavo (-) rotatory Peak 2; Example 162b; dextro (+) rotatory 163a.(-)- 7-amino-3-ethyl-2-methyl-5-((2-(1-(1-(((2-(methyl sulfinyl) ethyl) amino) methyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; 163b. <semantics>(+)<annotation encoding="application / x-tex">(+)< / annotation>< / semantics>-7-amino-3-ethyl-2-methyl-5-<semantics>((2−(1−(1−(((2−(methylsulfinyl))<annotation encoding="application / x-tex">((2-(1-(1-(((2-(methyl sulfinyl))< / annotation>< / semantics> ethyl) amino) methyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] Peak 1; Example 163a; leavo (-) rotatory Peak 2; Example 163b; dextro (+) rotatory 164. 7-amino-2-methyl-5-((2-(6-methylpyridin-2-yl) ethyl) amino)-3- propylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 165a (+)-7-amino-5-((2-(1-(2-(hydroxymethyl) cyclobutyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methyl-3-propylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; 165b. (-)-7-amino-5-((2-(1-(2-(hydroxymethyl) cyclobutyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methyl-3-propylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] Peak 1; Example 165a; dextro (+) rotatory Peak 2; Example 165b; leavo (-) rotatory 166. (R)-7-amino-3-ethyl-2-methyl-5-((2-(6-(((tetrahydrofuran-3-yl) oxy) methyl) pyridine-2-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; [Image disponible dans le document PDF, Image available in the PDF document] 167. (-) - 7-amino-3-ethyl-5-((2-(1-(4-(hydroxymethyl) tetrahydrofuran-3-yl)-5- methyl-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6- carbonitrile; and [Image disponible dans le document PDF, Image available in the PDF document] Example 167: Peak 1 : Levo (-) rotatory 168. (+) - 7-amino-3-ethyl-5-((2-(1-(4-(hydroxymethyl) tetrahydrofuran-3-yl)-5- methyl-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6- carbonitrile. [Image disponible dans le document PDF, Image available in the PDF document] Example 168: Peak 2 :Dextro (+) rotatory

[00058] In an embodiment of the present disclosure, there is provided a compound of Formula 1 or its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, stereoisomers, racemates, pharmaceutically active derivatives thereof as disclosed herein, for use as a medicament.

[00059] In an embodiment of the present disclosure, there is provided a compound of Formula I or its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, stereoisomers, racemates, pharmaceutically active derivatives thereof, as an antagonist of adenosine 2a receptor (A2aR) or adenosine 2b receptor (A2bR) or combination of adenosine 2a receptor <semantics>(A2aR)<annotation encoding="application / x-tex">(A_{2a}R)< / annotation>< / semantics> and adenosine 2b receptor <semantics>(A2bR)<annotation encoding="application / x-tex">(A_{2b}R)< / annotation>< / semantics>.

[00060] In an embodiment of the present disclosure, there is provided a compound of Formula I or its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, stereoisomers, racemates, pharmaceutically active derivatives thereof as disclosed herein for use in treating of a disease, disorder or condition selected from cancer, parkinson's disease, asthma, diabetes, and autoimmune disease mediated at least in part by adenosine 2a receptor (<semantics>A2aR<annotation encoding="application / x-tex">A_{2a}R< / annotation>< / semantics>) or adenosine 2b receptor (<semantics>A2bR<annotation encoding="application / x-tex">A_{2b}R< / annotation>< / semantics>) or combination of <semantics>A2aR<annotation encoding="application / x-tex">A_{2a}R< / annotation>< / semantics> and <semantics>A2bR<annotation encoding="application / x-tex">A_{2b}R< / annotation>< / semantics>.

[00061] In an embodiment of the present disclosure, there is provided a process of preparation of compounds of Formula I or its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, stereoisomers, racemates, pharmaceutically active derivatives thereof as disclosed herein, said process comprising: reacting Formula (A), and Formula (B) in the presence of a base to obtain the compounds of Formula I [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] + Formula (A) Formula (B) Formula (I) wherein R is selected from <semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics> alkyl, <semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics> cycloalkyl, <semantics>C5−10<annotation encoding="application / x-tex">C_{5-10}< / annotation>< / semantics> aryl, <semantics>C2−10<annotation encoding="application / x-tex">C_{2-10}< / annotation>< / semantics> heteroaryl, or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl; and the substituents are as disclosed herein.

[00062] In an embodiment of the present disclosure, there is provided a process of preparation of compounds of Formula I or its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, stereoisomers, racemates, pharmaceutically active derivatives thereof as disclosed herein, wherein the base is selected from triethylamine, diisopropylethylamine, pyridine, sodium carbonate, potassium carbonate, sodium hydroxide, potassium tertiarybutoxide potassium tertiarybutoxide, sodium hydride, lithium bis(trimethylsilyl)amide (LiHMDS), N-diisopropylethylamine, or combinations thereof.

[00063] In an embodiment of the present disclosure, there is provided a process of preparation of compounds of Formula I or its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, stereoisomers, racemates, pharmaceutically active derivatives thereof as disclosed herein, wherein the process is carried out in the presence of a solvent selected from isopropanol, methanol, n-butanol, dichloromethane, tetrahydrofuran, dimethylformaide, n-methylpyrrolidone, dimethyl sulfoxide, water, dioxane, acetonitrile, or combinations thereof.

[00064] In an embodiment of the present disclosure, there is provided a pharmaceutical composition comprising compounds of Formula I as disclosed herein and one or more additional therapeutic agent.

[00065] In an embodiment of the present disclosure, there is provided a pharmaceutical composition comprising compounds of Formula I with one or more additional therapeutic agent selected from chemotherapeutic agent, immune checkpoint inhibitors or combinations thereof. In another embodiment of the present disclosure, there is a pharmaceutical composition comprising compounds of Formula I as disclosed herein wherein the one or more additional therapeutic agent is chemotherapeutic agent or immune checkpoint inhibitors.

[00066] In an embodiment of the present disclosure, there is provided a pharmaceutical composition as disclosed herein, wherein the one or more additional therapeutic agent is the chemotherapeutic agent selected from phosphoinositide 3- kinase inhibitor (PI3K) inhibitor, tyrosine kinase inhibitor, signal transducer and activator of transcription 3 (Stat-3) inhibitor, topoisomerase inhibitors, Protein kinase B (AKT) inhibitor, c-Jun N-terminal kinase (JNK1 / K2) inhibitors, hypoxia- inducible factor 1 alpha (HIF-1a) inhibitor, extracellular signal-regulated kinase (ERK) inhibitor, poly ADP ribose polymerase -1((PARP-1) inhibitor, cisplatin, or oxaplatin.

[00067] In an embodiment of the present disclosure, there is provided a pharmaceutical composition as disclosed herein, wherein the one or more additional therapeutic agent is the immune checkpoint inhibitor selected from programmed death-1 (PD-1) inhibitor, programmed death-ligand 1 (PD-L1) inhibitor, anti-PD1 antibody, anti-PD-L1 antibody, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor, anti-CTLA-4 antibody, T cell immunoglobulin and ITIM domain (TIGIT) inhibitor, ecto-nucleoside triphosphate diphosphohydrolase 1(E- NTPDase, CD39) inhibitor, or ecto-5'-nucleotidase(Ecto5'NTase, CD79) inhibitor.

[00068] In an embodiment of the present disclosure, there is provided a pharmaceutical composition comprising the compounds of Formula I or its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, stereoisomers, pharmaceutically active derivatives thereof with one or more additional therapeutic agent selected from chemotherapeutic agent or immune checkpoint inhibitors and wherein the one or more additional therapeutic agent selected from phosphoinositide 3-kinase inhibitor (PI3K) inhibitor, tyrosine kinase inhibitor, signal transducer and activator of transcription 3 (Stat-3) inhibitor, topoisomerase inhibitors, Protein kinase B (AKT) inhibitor, c-Jun N-terminal kinase (JNK1 / K2) inhibitors, hypoxia-inducible factor 1 alpha (HIF-1a) inhibitor, extracellular signal-regulated kinase (ERK) inhibitor, poly ADP ribose polymerase -1( (PARP-1) inhibitor, cisplatin, oxaplatin, programmed death-1 (PD-1) inhibitor, programmed death-ligand 1 (PD-L1) inhibitor, anti-PD1 antibody, anti-PD-L1 antibody, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)inhibitor, anti- CTLA-4 antibody, T cell immunoglobulin and ITIM domain (TIGIT) inhibitor, ecto-nucleoside triphosphate diphosphohydrolase 1(E-NTPDase, CD39) inhibitor, or ecto-5'-nucleotidase(Ecto5'NTase, CD79) inhibitor.

[00069] In an embodiment of the present disclosure, there is provided a method of treatment and / or prevention of a condition mediated by adenosine receptor or a proliferative disorder or a disease or cancer, comprising administering to a subject suffering from a condition mediated by adenosine receptor or a disease or proliferative disorder or a disease or cancer, a therapeutically effective amount of the compounds of Formula I as disclosed herein or the pharmaceutical composition comprising the compounds of Formula I with one or more additional therapeutic agent.

[00070] In an embodiment of the present disclosure, there is provided a method of treatment and / or prevention of a condition mediated by adenosine receptor or a proliferative disorder or a disease or cancer, comprising administering to a subject suffering from a condition mediated by adenosine receptor or proliferative disorder or a disease or cancer, a therapeutically effective amount of the compounds of Formula I as disclosed herein or the pharmaceutical composition comprising the compounds of Formula I with one or more additional therapeutic agent, wherein the condition mediated by adenosine receptor or a proliferative disorder or a disease or a cancer at least in part by adenosine 2a receptor <semantics>(A2aR)<annotation encoding="application / x-tex">(A_{2a}R)< / annotation>< / semantics>, adenosine 2b receptor <semantics>(A2bR)<annotation encoding="application / x-tex">(A_{2b}R)< / annotation>< / semantics>, or combinations thereof.

[00071] In an embodiment of the present disclosure, there is provided a method of treatment and / or prevention of a condition mediated by adenosine receptor or a proliferative disorder or cancer, comprising administering to a subject suffering from a condition mediated by adenosine receptor or a disease or proliferative disorder or cancer, a therapeutically effective amount of the compounds of Formula I as disclosed herein or the pharmaceutical composition as disclosed herein, wherein the compounds of Formula (I) administered in an effective amount to reverse or stop the progression of either the adenosine 2a receptor <semantics>(A2aR)<annotation encoding="application / x-tex">(A_{2a}R)< / annotation>< / semantics>, or adenosine 2b receptor <semantics>(A2bR)<annotation encoding="application / x-tex">(A_{2b}R)< / annotation>< / semantics>, or both mediated immunosuppression.

[00072] In an embodiment of the present disclosure, there is provided a method of treatment and / or prevention of a condition mediated by adenosine receptor or a proliferative disorder or a disease or cancer, comprising administering to a subject suffering from a condition mediated by adenosine receptor or proliferative disorder or a disease or cancer, a therapeutically effective amount of the compounds of Formula I as disclosed herein or the pharmaceutical composition as disclosed herein, wherein the proliferative disorder or disease is cancer or an immune response related disorder or disease or condition.

[00073] In an embodiment of the present disclosure, there is provided a method of treatment and / or prevention of a condition mediated by adenosine receptor or a proliferative disorder or disease or cancer, comprising administering to a subject suffering from a condition mediated by adenosine receptor or a disease or proliferative disorder or cancer, a therapeutically effective amount of the compounds of Formula I as disclosed herein or the pharmaceutical composition as disclosed herein, wherein the cancer is of adrenal gland, brain, bladder, breast, bone, colon, endometrial, oesophagus, head, gastric, kidney, liver, lung, mouth, muscle, neck, pancreas, prostate, retinal, skin, thyroid or white blood cells and said immune related disease, disorder or condition is selected from the group consisting of allergies, alzheimer, asthma, crohn's disease, colitis, chronic obstructive pulmonary disease, diabetic kidney disorders, glaucoma, lupus, rheumatoid arthritis, multiple sclerosis, pain, panic disorder, pancreatitis, parkinson disease, psoriasis, systemic sclerosis, and ulcerative colitis.

[00074] In an embodiment of the present disclosure, there is provided a use of the compounds of Formula I as disclosed herein or the pharmaceutical composition as disclosed herein for treatment of a condition mediated by adenosine receptor A2aR; treatment and / or prevention of a proliferative disorder or disease or cancer or immune related disorder or disease or condition; or treatment of cancer together with other clinically relevant cytotoxic agents or non-cytotoxic agents.

[00075] In an embodiment of the present disclosure, there is provided a use of the compounds of Formula I as disclosed herein or the pharmaceutical composition as disclosed herein for treatment of a condition mediated by adenosine receptor A2bR; treatment and / or prevention of a proliferative disorder or disease or cancer or immune related disorder or disease or condition; or treatment of cancer together with other clinically relevant cytotoxic agents or non-cytotoxic agents.

[00076] In an embodiment of the present disclosure, there is provided a use of the compounds of Formula I as disclosed herein or the pharmaceutical composition as disclosed herein for treatment of a condition mediated by adenosine receptors A2aR and A2bR; treatment and / or prevention of a proliferative disorder or disease or cancer or immune related disorder or disease or condition; or treatment of cancer together with other clinically relevant cytotoxic agents or non-cytotoxic agents. EXAMPLES

[00077] As used herein the symbols and conventions used in these processes, schemes and examples are consistent with those used in the contemporary scientific literature. Unless otherwise noted, all starting materials were obtained from commercial suppliers and used without further purification. Specifically, the following abbreviations may be used in the examples and throughout the specification: Abbreviations The following abbreviations are employed in the examples and elsewhere herein: TLC- thin layer chromatography; HPLC - high pressure liquid chromatography; MPLC - medium pressure liquid chromatography; NMR - nuclear magnetic resonance spectroscopy; DMSO - dimethylsulfoxide; CDCl3 - deuterated chloroform; MeOD -deuterated methanol, i.e. D3COD; MS - mass spectroscopy; ESP (or ES) - electrospray; EI - electron impact; APCI - atmospheric pressure chemical ionization; THF - tetrahydrofuran; DCM - dichloromethane; MeOH - methanol; DMF -dimethylformamide; EtOAc - ethyl acetate; LC / MS - liquid chromatography / mass spectrometry; h - hour(s); min is minute(s); <semantics>d−day(s);<annotation encoding="application / x-tex">d - day(s);< / annotation>< / semantics> MTBD - N-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene; TFA - trifluoroacetic acid; v / v - ratio of volume / volume; Boc - t-butoxycarbonyl; Cbz - benzyloxycarbonyl; Bz - benzoyl; Atm - atmospheric pressure; rt -room temperature; mg - milligram; g denotes gram; μL - microliter; mL - milliliter; L - liter; μM - micromolar; nM-Nanomolar mM - millimolar; M denotes molar; DMAP- dimethyaminopyridine; TBDMS -tert-butyldimethylsilyl N - normal; and nm - nanometer.

[00078] The following examples provide the details about the synthesis, activities and applications of the compounds of the present disclosure. It should be understood the following is representative only, and that the invention is not limited by the details set forth in these examples. Materials and methods:

[00079] Evaporations were carried out by rotary evaporation in vacuo and work up procedures were carried out after removal of residual solids by filtration; temperatures are quoted as °C; operations were carried out at room temperature, that is typically in the range 18 to 26 °C and without the exclusion of air unless otherwise stated, or unless the skilled person would otherwise work under an inert atmosphere; column chromatography (by the flash procedure) was used to purify compounds and was performed on Merck Kieselgel silica (Art. 9385) unless otherwise stated; in general, the course of reactions was followed by TLC, HPLC, or LC / MS and reaction times are given for illustration only; yields are given for illustration only and are not necessarily the maximum attainable; the structure of the end products of the invention was generally confirmed by NMR and mass spectral techniques. Proton magnetic resonance spectra were generally determined in DMSO d6 unless otherwise stated, using a Bruker DRX 300 spectrometer or a Bruker DRX-400 spectrometer, operating at a field strength of 300 MHz or 400 MHz, respectively. In cases where the NMR spectrum is complex, only diagnostic signals are reported. Chemical shifts are reported in parts per million downfield from tetramethylsilane as an external standard (* scale) and peak multiplicities are shown thus: s, singlet; d, doublet; dd, doublet of doublets; dt, doublet of triplets; dm, doublet of multiplets; t, triplet, m, multiplet; br, broad. Fast atom bombardment (FAB) mass spectral data were generally obtained using a Platform spectrometer (supplied by Micromass) run in electrospray and, where appropriate, either positive ion data or negative ion data were collected or using Agilent 1100 series LC / MS equipped with Sedex 75ELSD, and where appropriate, either positive ion data or negative ion data were collected. The lowest mass major ion is reported for molecules where isotope splitting results in multiple mass spectral peaks (for example when chlorine is present). Reverse Phase HPLC was carried out using YMC Pack ODS AQ (100x20 mmID, S 5Å particle size, 12 nm pore size) on Agilent instruments; each intermediate was purified to the standard required for the subsequent stage and was characterized in sufficient detail to confirm that the assigned structure was correct; purity was assessed by HPLC, TLC, or NMR and identity was determined by infrared spectroscopy (IR), mass spectroscopy or NMR spectroscopy as appropriate. General process for the preparation of the compounds of Formula (A)

[00080] Compounds of formula (A) was prepared from formula (F) via oxidation using appropriate oxidizing agents (e.g., mCPBA) and the compounds of formula (F) was synthesized by reacting compounds of formula (D) with formula (E) in presence of appropriate base (e.g., pyridine). The formula (D) was obtained by treating formula (C) with carbon disulphide and methyl iodide in presence of appropriate base (e.g., sodium hydride) (Scheme 1). [Image disponible dans le document PDF, Image available in the PDF document] General process for the preparation of the compounds of Formula B

[00081] The preparation of compounds of Formula (B) may be prepared in a variety of ways and many of them are commercially available. The generic route for Formula (B) is given Scheme 2 wherein, the formula (B) was obtained by treating a carbonyl compound of Formula (B1) with an amine of Formula (B2) with suitable reducing reagent. [Image disponible dans le document PDF, Image available in the PDF document] Scheme 2 Further, the processes for one of the representative compounds of formula(B) wherein A is six membered rings shown as formula (N) in scheme 3. [Image disponible dans le document PDF, Image available in the PDF document] Scheme 3

[00082] The compounds of Formula (B) were obtained by reducing either compounds of Formula (H) or (J) with appropriate reducing agents. The compounds of Formula (H) were obtained by treating compounds Formula (G) with nitromethane wherein Q is an aldehyde. The compounds of Formula (J) were obtained by treating compounds of Formula (G) with acetonitrile in presence appropriate alkali metal base (E.g., nBuLi) where in Q is a halogen (E.g., Br or I).

[00083] In similar to the process of making compounds of Formula(I) the [Image disponible dans le document PDF, Image available in the PDF document] Scheme 4 processes for one of the representative compounds of Formula(B) with five membered rings shown as Formula (M) in scheme 4.

[00084] The examples shown above illustrate some methods useful for the synthesis of compounds of Formula (A) and compound (B) which may be used for the synthesis of compounds of Formula (I). Where a particular solvent or reagent is shown or referred to in the accompanying text, it is to be understood that the chemist of ordinary skill in the art will be able to modify and / or replace that solvent or reagent, as necessary.

[00085] In another embodiment, the compounds of Formula I, can be prepared reacting compounds of Formula (B) with compounds of Formula (A), in the presence of appropriate base and solvents as shown scheme 5. [Image disponible dans le document PDF, Image available in the PDF document] Scheme 5

[00086] The present disclosure provides a process for the preparation of compounds of Formula (I) and the compounds of Formula (I) which may be prepared in a variety of ways. The processes and examples shown below illustrate some methods useful for the synthesis of compounds of Formula (I) and intermediates which may be used for the synthesis of compounds of Formula (I). Where a particular solvent or reagent is shown or referred to in the accompanying text, it is to be understood that the chemist of ordinary skill in the art will be able to modify and / or replace that solvent or reagent as necessary Synthesis of Intermediates: Synthesis of 7-amino-2,3-dimethyl-5-(methyl sulfonyl) pyrazolo[1,5-a] pyrimidine-6-carbonitrile. (I) [Image disponible dans le document PDF, Image available in the PDF document] Step-1: Synthesis of 2-(bis(methylthio)methylene) malononitrile (Ia)

[00087] A stirred solution of KOH (16.98 g, 302.75 mmol) in water (100 mL) was cooled to 0 °C and was added malononitrile (10 g, 151.37 mmol) in dry THF (20 mL) was added dropwise over a period of 30 min under N2 atmosphere. The reaction was stirred at room temperature for 1 h and was added <semantics>CS2<annotation encoding="application / x-tex">CS_2< / annotation>< / semantics> (17.2 g, 227.06 mmol) at 0 °C. After stirring the reaction mixture at room temperature for about 1 h dimethylsulphate (24.8 g, 196.7 mmol) was added and stirring was continued for another 4h at room temperature. After completion, the reaction mixture was quenched with ice cold water and the solid precipitated was filtered and dried under vacuo to afford the compound Ia (8 g, 31%) as yellow solid, which was taken forward for further step without purification. Step-2: Synthesis of 7-amino-2,3-dimethyl-5-(methylthio) pyrazolo[1,5-a] pyrimidine-6-carbonitrile (Ic)

[00088] To a stirred solution of Ia (10 g, 58.8 mmol) in ethanol (20 mL) was added Ib (4.57 g, 41.17 mmol) at room temperature under N2 atmosphere. The resulted mixture was heated at 120 °C for 6 h. After that the reaction mixture was cooled to room temperature and the solid precipitated was filtered and washed with ethanol to give off-white solid, it was purified by column chromatography on silica gel (230-400 mesh, 45% ethyl acetate in pet ether) to obtained Ic (3.1 g, 32%); LC- MS Calculated. for <semantics>C10H11N5S<annotation encoding="application / x-tex">C_{10}H_{11}N_5S< / annotation>< / semantics>: 233.29; Observed.: 234.0; [M++H]. 1H NMR (400) MHz, DMSO-D6): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 8.60 (s,2H), 2.68 (s, 3H), 2.37 (s, 3H), 2.13 (s, 3H). Step-3: Synthesis of 7-amino-2,3-dimethyl-5-(methyl sulfonyl) pyrazolo[1,5-a] pyrimidine-6-carbonitrile. (I)

[00089] A stirred solution of Ic (5 g, 21.45 mmol) in dichloromethane (50 mL) was cooled to 0 °C and was added m-CPBA (11.07 g, 64.37 mmol) under N2 atmosphere. The resulted mixture was stirred at room temperature for 3 h. After that the reaction mixture was quenched with 10% NaHCO3 solution and extracted with DCM (2 x 300 mL). The combined organic layer was dried over Na2SO4 and concentrated under vacuo to afford the compound I (3.1 g, 54%) as an off-white solid which was taken forward for further step without purification. LC-MS Calculated. for <semantics>C10H11N5O2S<annotation encoding="application / x-tex">C_{10}H_{11}N_5O_2S< / annotation>< / semantics>: 265.29; Observed.: 266.0; [M++H].1H NMR (400) MHz, DMSO-D6): δ 9.1 (br s, 2H), 3.42 (s, 3H), 2.40 (s, 3H), 2.17 (s, 3H). Synthesis of 7-amino-3-ethyl-2-methyl-5-(methyl sulfonyl) pyrazolo[1,5- a|pyrimidine-6-carbonitrile.(II) [Image disponible dans le document PDF, Image available in the PDF document] Step-1: 2-ethyl-3-oxobutanenitrile (IIa)

[00090] To a three neck RB flask, LDA (2M in THF, 36.17 ml, 0.0723 mol) was taken and THF (82.5 ml) was added and cooled to -78 °C. To this solution, butyronitrile (5 g, 0.0723 mol) in THF (10 ml) was added dropwise at -78 °C and the reaction mixture was stirred at -78 °C for 1 h. Then, ethyl acetate (6.42 ml, 0.0657 mol) was added dropwise at -78 °C and the reaction mixture was stirred at -78 °C for 2 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled to 0 °C and quenched with saturated solution of NH4Cl (25 ml) and extracted with ethyl acetate (50 ml x 3). The organic layer was dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure to get the title compound IIa as yellow viscous oil; Yield: (8 g, 100%). 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 3.237-3.205 (q, 1H), 2.499 (s, 3H), 1.153-1.137 (d, J) <semantics>=6.4 Hz,3H,0.973−0.937 (t, J=7.2 Hz,3H).<annotation encoding="application / x-tex">= 6.4 \text{ Hz}, 3\text{H}, 0.973-0.937 \text{ (t, } J = 7.2 \text{ Hz}, 3\text{H}).< / annotation>< / semantics> Step-2: 4-ethyl-5-methyl-1H-pyrazol-3-amine (IIb)

[00091] To a stirred solution of 2-ethyl-3-oxobutanenitrile 3 (8 g) in EtOH (80 ml) was added hydrazine hydrate (23.80 ml) and the reaction mixture was heated at 120 °C for 1.5 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled to rt and evaporated under reduced pressure. The residue was dissolved in 6N HCl (25 ml) and washed with ethyl acetate (3 x 50 ml). Aq. layer was basified to pH >7 using aqueous ammonia solution and extracted with ethyl acetate (3 x 50 ml). The organic layer was dried with Na2SO4, filtered, and evaporated under reduced pressure to get the title compound Ha as light brown viscous liquid was used in the next step without further purification; Yield: (8.1 g, 90%). H NMR (400 MHz, CD3OD): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 2.354 <semantics>(q,J=7.2 Hz,2H),2.110 (s, 3H),1.087−1.049 (t, J=7.2 Hz,3H).<annotation encoding="application / x-tex">(q, J = 7.2 \text{ Hz}, 2\text{H}), 2.110 \text{ (s, 3H)}, 1.087-1.049 \text{ (t, } J = 7.2 \text{ Hz}, 3\text{H}).< / annotation>< / semantics> Step-3: 2-(Bis(methylthio) methylene) malononitrile (Ia)

[00092] To a stirred solution of malononitrile (5.0 g, 0.075 mol) in DMSO (50 ml) cooled to 0 °C was added K2CO3 (11.4 g, 0.0833 mol), CS2 (5.03 g, 0.0833 mol) and stirred at rt for 3 h. Then the reaction mixture cooled to 0 °C and MeI (9.4) ml, 0.1514 mol) was added and the reaction mixture was stirred at rt for 16 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was poured into ice cold water (50 ml) and the precipitate formed was filtered, washed with cold water and dried to get the compound Ia as brick red solid which was used in the next step without further purification; Yield: (6.2 g, 51%). Step-4: 7-amino-3-ethyl-2-methyl-5-(methylthio) pyrazolo[1,5-a] pyrimidine- 6-carbonitrile (IIc)

[00093] To a stirred solution of 2-(bis(methylthio)methylene) malononitrile Ia (11.0 g, 0.0647 mol) in pyridine (80 ml) was added 4-ethyl-5-methyl-1H- pyrazol-3-amine (8.1 g, 0.0647 mol) and the reaction mixture was heated at 120°C for 2.5 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was evaporated, and the residue was diluted with water (150) ml) and resulting solid was stirred for 2h at 10-15 °C. Filtered the solid and azeotroped with toluene (2 x 50 ml) to get dried title compound Hc. Yield: (12.3 g, 78 %). 1H NMR (400 MHz, CD3OD): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 2.691-2.634 (q, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics> = 7.6 Hz, 2H), 2.583 (s, 3H), 2.371 (s, 3H), 1.257-1.205 (t, <semantics>J=8<annotation encoding="application / x-tex">J = 8< / annotation>< / semantics> Hz, 3H). Step-5: 7-amino-3-ethyl-2-methyl-5-(methyl sulfonyl) pyrazolo [1,5-a] pyrimidine-6-carbonitrile. (II)

[00094] To a stirred solution of 7-amino-3-ethyl-2-methyl-5-(methylthio) pyrazolo[1,5-a] pyrimidine-6-carbonitrile IIc (11.2 g, 0.0481 mol) in DCM (120 ml) cooled to 0 °C, was added m-CPBA (33.20 g, 0.19 mol) slowly and the reaction mixture was stirred at rt for 30 min. The progress of the reaction was monitored by TLC (polar spot). After completion, the reaction mixture was quenched with NaHCO3 (150 ml) and extracted with DCM (150 ml x 3). The organic layer was dried with Na2SO4, filtered, and evaporated under reduced pressure. The crude material was purified using 50% ethyl acetate in hexane to get pure title compound. Yield: (9.5g, 70%). LC_MS Calculated for <semantics>C11H13N5O2S<annotation encoding="application / x-tex">C_{11}H_{13}N_5O_2S< / annotation>< / semantics>: 279.10; Observed: 280.10 [M++H]. H NMR (400 MHz, CD3OD): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 3.385 (s, 3H), 2.777- <semantics>2.721(q,J=7.2Hz,2H),2.463(s,3H),1.260−1.230(t,J=7.2Hz,3H).<annotation encoding="application / x-tex">2.721 (q, J = 7.2 Hz, 2H), 2.463 (s, 3H), 1.260-1.230 (t, J = 7.2 Hz, 3H).< / annotation>< / semantics> Synthesis of 7-amino-3-isopropyl-2-methyl-5-(methyl sulfonyl) pyrazolo[1,5-a] pyrimidine-6-carbonitrile. (III) [Image disponible dans le document PDF, Image available in the PDF document] Step-1: 2-acetyl-3-methylbutanenitrile. (IIIa)

[00095] To a three neck RB flask, LDA (2M in THF, 29.8 mL, 0.0595 mol) was taken and THF (100 mL) was added and cooled to -78 °C. To this solution, 3- methylbutanenitrile (CAS:625-28-5, 25 g, 0.0595 mol) in THF (40 mL) was added dropwise at -78 °C and the reaction mixture was stirred at -78 °C for 1 h. Then, ethyl acetate (CAS:141-78-6, 5.2 mL, 0.0536 mol) was added dropwise at -78 °C and the reaction mixture was stirred at -78 °C for 1 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled to 0 °C and quenched with saturated solution of NH4Cl (50 mL) and extracted with ethyl acetate (80 mL x 3). The organic layer was dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure to get the title compound IIIa as yellow viscous oil; Yield: (6.5 g, 87%). LC_MS Calculated for C7H11NO: 125.08; Observed:124.10 [M-H]. Step-2: 4-isopropyl-5-methyl-1H-pyrazol-3-amine. (IIIb)

[00096] To a stirred solution of 2-acetyl-3-methylbutanenitrile IIIa (6.5 g, 0.0520 mol) in EtOH (65 mL) was added hydrazine hydrate (19.5 mL, 0.00438 mol) and the reaction mixture was heated at 120 °C for 1.5 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled to rt and evaporated under reduced pressure. The residue obtained was diluted with water (100 mL) and extracted with ethyl acetate (80 mL x 3). The organic layer was dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure to get tittle compound IIIb as light brown viscous liquid. This crude product was used as such for the next step without further purification; Yield: (4.5 g, 52%). H NMR (400) MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 5.18 (bs, 2H), 3.18 (d, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>=7.6 Hz, 1H), 2.29-2.04 (m, 1H), 1.83 (s, 3H), <semantics>1.22<annotation encoding="application / x-tex">1.22< / annotation>< / semantics> (d, <semantics>J=10.0<annotation encoding="application / x-tex">J=10.0< / annotation>< / semantics> Hz, 1H), <semantics>1.11<annotation encoding="application / x-tex">1.11< / annotation>< / semantics> (d, <semantics>J=6.8<annotation encoding="application / x-tex">J=6.8< / annotation>< / semantics> Hz, 3H), <semantics>1.01<annotation encoding="application / x-tex">1.01< / annotation>< / semantics> (d, <semantics>J=6.8<annotation encoding="application / x-tex">J=6.8< / annotation>< / semantics> Hz, 3H). Step-3: 2-(Bis(methylthio) methylene) malononitrile. (Ia)

[00097] To a stirred solution of malononitrile (5.0 g, 0.075 mol) in DMSO (50 ml) cooled to 0 °C was added K2CO3 (11.4 g, 0.0833 mol), CS2 (5.03 g, 0.0833 mol) and stirred at rt for 3 h. Then the reaction mixture cooled to 0 °C and MeI (9.4) ml, 0.1514 mol) was added and the reaction mixture was stirred at rt for 16 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was poured into ice cold water (50 ml) and the precipitate formed was filtered, washed with cold water and dried to get the compound Ia as brick red solid which was used in the next step without further purification; Yield: (6.2 g, 51%). Step-4: 7-amino-3-isopropyl-2-methyl-5-(methylthio) pyrazolo[1,5- a]pyrimidine-6-carbonitrile. (IIIc)

[00098] To a stirred solution of 2-(bis(methylthio)methylene) malononitrile Ia (6.1 g, 0.0360 mol) in pyridine (50 mL) and 4-isopropyl-5-methyl-1H-pyrazol- 3-amine IIIb (4.5g, 0.0360 mol) and the reaction mixture was heated at 120 °C in for 1.5 h. The progress of the reaction was monitored by TLC. After completion, to the reaction 200 mL water was added and the pale-yellow residue formed was collected by filtration. The solid was washed with fresh water (200 mL) and dried under vacuo to afford the desired compound as a pale-yellow solid. The crude material was used in the next step without further purification; Yield: (6.0 g, 71%). LC_MS Calculated for C12H15N5S: 261.10; Observed:262.10 [M+H] +. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 6.20 (bs, 2H), 3.09-3.06 (m, 1H), 2.62 (s, 3H), 2.40 (s, 3H), <semantics>1.38(d,J=6.8Hz,6H).<annotation encoding="application / x-tex">1.38 \, (d, J=6.8 \, Hz, 6H).< / annotation>< / semantics> Step-5: 7-amino-3-isopropyl-2-methyl-5-(methyl sulfonyl) pyrazolo[1,5-a] pyrimidine-6-carbonitrile. (III)

[00099] To a stirred solution of 7-amino-3-isopropyl-2-methyl-5- (methylthio) pyrazolo[1,5-a] pyrimidine-6-carbonitrile IIIc (6.0 g, 0.023 mol) in DCM (60 mL), cooled to 0 °C, was portion wise added m-CPBA (16.0 g, 0.092 mol) and the reaction mixture was stirred at rt for 2 h. The progress of the reaction was monitored by TLC (polar spot). After completion, the reaction mixture was quenched with NaHCO3 (100 mL) and extracted with DCM (80 mL x 3). The organic layer was dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure. The crude material was subjected to silica gel (100-200) column chromatography using ethyl acetate (0-30%) in n-hexane to afford the desired compound III as an off-white solid; Yield: (1.5g, 22%). LC_MS Calculated for C12H15N5O2S: 293.09; Observed: 294.05 [M+H] +. 1H NMR (400 MHz, DMSO- D6): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 9.18 (bs, 2H), 3.42 (s, 3H), 3.15-3.12 (m, 1H), 2.45 (s, 3H), 1.34 (d, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>=6.8 Hz, 6H). Synthesis of 7-amino-3-isobutyl-2-methyl-5-(methyl sulfonyl) pyrazolo[1,5- a|pyrimidine-6-carbonitrile. (1V) [Image disponible dans le document PDF, Image available in the PDF document] Step-1: 2-Acetyl-4-methylpentanenitrile. (IVa) [000100] To a three neck RB flask, LDA (2M in THF, 2.5 ml, 0.00514 mol) was taken and THF (10 ml) was added and cooled to -78 °C. To this solution, 4- methylpentanenitrile (CAS:542-54-1, 0.5 g, 0.00514 mol) in THF (4 ml) was added dropwise at -78 °C and the reaction mixture was stirred at -78 °C for 1 h. Then, ethyl acetate (CAS:141-78-6, 0.45 ml, 0.00468 mol) was added dropwise at -78 °C and the reaction mixture was stirred at -78 °C for 2 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled to 0 °C and quenched with saturated solution of NH4Cl (5 ml) and extracted with ethyl acetate (20 ml x 3). The organic layer was dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure to get the title compound IVa as yellow viscous oil; Yield: (0.478 g, 66%). 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 3.46-3.42 (m, 1H), 2.40 (s, 3H), 1.89-1.76 (m, 2H), 1.70-1.65 (m, 1H), 1.0 (d, <semantics>J=6.4<annotation encoding="application / x-tex">J = 6.4< / annotation>< / semantics> Hz, 3H), <semantics>0.96(d,J=6.4Hz,3H).<annotation encoding="application / x-tex">0.96 (d, J = 6.4 Hz, 3H).< / annotation>< / semantics> Step-2: 4-Isobutyl-5-methyl-1H-pyrazol-3-amine. (IVb) [000101] To a stirred solution of 2-acetyl-4-methylpentanenitrile IVa (0.470) g, 0.00337 mol) in EtOH (20 ml) was added hydrazine hydrate (0.219 g, 0.00438 mol) and the reaction mixture was heated at 90 °C for 15 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled to rt and evaporated under reduced pressure. The residue obtained was diluted with water (10 ml) and extracted with ethyl acetate (20 ml x 3). The organic layer was dried with Na2SO4, filtered, and evaporated under reduced pressure to get crude material IVb as light brown viscous liquid. The crude product obtained was taken as such for next step without further purification; Yield: (0.478 g, 92%). 1H NMR (400 MHz, DMSO-D6): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 10.85 (bs, 1H), 4.13 (bs, 2H), 2.04 (d, <semantics>J=7.2<annotation encoding="application / x-tex">J = 7.2< / annotation>< / semantics> Hz, 2H), 1.98 (s, 3H), 1.69-1.62 (m, 1H), 0.83 (d, <semantics>J=6.8<annotation encoding="application / x-tex">J = 6.8< / annotation>< / semantics> Hz, 6H). Step-3: 2-(Bis(methylthio) methylene) malononitrile. (Ia) [000102] To a stirred solution of malononitrile (CAS:109-77-3, 5.0 g, 0.075 mol) in DMSO (50 ml) cooled to 0 °C was added K2CO3 (11.4 g, 0.0833 mol), CS2 (5.03 g, 0.0833 mol) and stirred at rt for 3 h. Then the reaction mixture cooled to 0 °C and methyl Iodide (9.4 ml, 0.1514 mol) was added and the reaction mixture was stirred at rt for 16 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was poured into ice cold water (50 ml) and the precipitate formed was filtered, washed with cold water and dried to get the compound Ia as brick red solid which was used in the next step without further purification; Yield: (6.2 g, 51%). Step-4: 7-Amino-3-isobutyl-2-methyl-5-(methylthio) <semantics>pyrazolo[1,5−a]<annotation encoding="application / x-tex">pyrazolo[1,5-a]< / annotation>< / semantics> pyrimidine-6-carbonitrile. (IVc) [000103] To a stirred solution of 2-(bis(methylthio)methylene) malononitrile Ia (1.0 g, 0.0065 mol) in EtOH (10 ml) was added TEA (1.81 ml, 0.013 mol) and 4-isobutyl-5-methyl-1H-pyrazol-3-amine IVb (1.1 g, 0.0065 mol) and the reaction mixture was heated at 100°C in microwave for 1 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was evaporated, and the residue was diluted with water (20 ml) and extracted with ethyl acetate (20 ml) x 3). The organic layer was dried with Na2SO4, filtered, and evaporated under reduced pressure to get crude compound IVc. The crude product obtained was taken for next step without further purification; Yield: (1.64 g, 92 %). LC_MS Calculated for C13H17N5S: 275.12; Observed: 276.20 [M++H]. 1H NMR (400 MHz, DMSO- D6): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 8.51 (bs, 2H), 2.53-2.50 (m, 2H), 2.45 (d, <semantics>J=7.2<annotation encoding="application / x-tex">J = 7.2< / annotation>< / semantics> Hz, 2H), 2.37 (t, <semantics>J=3.6<annotation encoding="application / x-tex">J = 3.6< / annotation>< / semantics> Hz, 1H), 2.29 (s, 3H), 1.95-1.88 (m, 1H), 0.88-0.85 (m, 6H). Step-5: 7-Amino-3-isobutyl-2-methyl-5-(methyl sulfonyl) pyrazolo[1,5-a] pyrimidine-6-carbonitrile (IV) [000104] To a stirred solution of 7-amino-3-isobutyl-2-methyl-5-(methylthio) pyrazolo[1,5-a] pyrimidine-6-carbonitrile IVc (0.65 g, 0.00236 mol) in DCM (10 ml) cooled to 0 °C, was added m-CPBA (1.0 g, 0.0059 mol) slowly and the reaction mixture was stirred at rt for 16h. The progress of the reaction was monitored by TLC (polar spot). After completion, the reaction mixture was quenched with NaHCO3 (50 ml) and extracted with DCM (50 ml x 3). The organic layer was dried with Na2SO4, filtered, and evaporated under reduced pressure to get the title compound IV. The crude product was used as such for the next step without further purification; Yield: (0.703 g, 97 %). LC_MS Calculated for C13H17N5O2S: 307.11; Observed:308.15 [M++H]. 1H NMR (400 MHz, DMSO-D6): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 9.19 (bs, 2H), 3.40 (s, 3H), 2.53-2.52 (m, 2H), 2.41 (s, 3H), 1.95-1.92 (m, 1H), 0.96-0.87 (m, 6H). Synthesis of 7-amino-3-(cyclopropyl methyl)-2-methyl-5-(methyl sulfonyl) pyrazolo[1,5-a] pyrimidine-6-carbonitrile. (V) [Image disponible dans le document PDF, Image available in the PDF document] Step-1: 2-cyclopropylethyl 4-methylbenzenesulfonate (Va) [000105] To a stirred solution of 2-cyclopropylethan-1-ol 1 (CAS: 2566-44-1, 5.0 g, 0.0581 mol) in DCM (75 mL) cooled to 0 °C was added pyridine (12.6 mL) followed by an addition of p-TsCl (8.9 g, 0.0470 mol) and the reaction mixture was stirred at rt for 16 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was diluted with diethyl ether (100 ml) and washed sequentially with water (50 mL), 10 % HCl (50 mL), water (10 ml) and dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure to get compound Va as colorless liquid. The crude product obtained was taken for the next step without further purification; Yield: (8.6 g, 66%). LC_MS Calculated for C12H16O3S: 140.32; Observed.141.15 [M++H]. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.81 (d, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>=8.4 Hz, 2H), <semantics>7.35<annotation encoding="application / x-tex">7.35< / annotation>< / semantics> (d, <semantics>J=8.4<annotation encoding="application / x-tex">J=8.4< / annotation>< / semantics> Hz, <semantics>2<annotation encoding="application / x-tex">2< / annotation>< / semantics>H), <semantics>4.9<annotation encoding="application / x-tex">4.9< / annotation>< / semantics> (t, <semantics>J=6.4<annotation encoding="application / x-tex">J=6.4< / annotation>< / semantics> Hz <semantics>2<annotation encoding="application / x-tex">2< / annotation>< / semantics>H), <semantics>2.46<annotation encoding="application / x-tex">2.46< / annotation>< / semantics> (s, <semantics>3<annotation encoding="application / x-tex">3< / annotation>< / semantics>H), <semantics>1.56−1.51<annotation encoding="application / x-tex">1.56-1.51< / annotation>< / semantics>(m, <semantics>2<annotation encoding="application / x-tex">2< / annotation>< / semantics>H), <semantics>0.67−0.65<annotation encoding="application / x-tex">0.67-0.65< / annotation>< / semantics> (m, 1H), 0.40-0.39 (m, 2H), 0.04-0.01 (m, 2H). Step-2: 3-Cyclopropylpropanenitrile (Vb) [000106] To a stirred solution of 2-cyclopropylethyl 4- methylbenzenesulfonate Va (8.6 g, 0.0357 mol) in DMF (32 mL) was added TBAI (0.526 g) followed by an addition of sodium cyanide (5.2 g, 0.107 mol) and the reaction mixture was heated at 90 °C for 16 h. The progress of the reaction was monitored by TLC analysis. After completion, the reaction mixture was diluted with diethyl ether (150 mL) and washed with water (100 mL x 3), brine (100 mL) and dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure to get desired product Vb as light brown viscous liquid. This crude product obtained was taken for the next step without further purification; Yield: (3.3 g, 97%). 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 3.74-3.72 (m, 1H), 2.42 (t, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>=6.8 Hz 2H), 1.59-1.51 (m, 2H), 0.86-0.81 (m, 1H), 0.56-0.53 (m, 2H), 0.16-0.13 (m, 2H). Step-3: 2-(cyclopropyl methyl)-3-oxobutanenitrile (Vc) [000107] A three neck RB flask was charged with LDA (2M sol in THF, 15.35) mL, 0.0315 mol) and THF (60 mL) under N2 atmosphere. The resulting mixture was cooled to -78 °C and a solution of 3-cyclopropylpropanenitrile Vb (3.0 g, 0.0315 mol) in THF (24 mL) was dropwise added maintaining temperature to -78 °C. The reaction mixture was stirred at -78 °C for 1 h and ethyl acetate (CAS: 141-78-6, 2.52 g, 0.0287 mol) was dropwise added at -78 °C. The resulting mixture was stirred at -78 °C for 2 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled to 0 °C and quenched with saturated solution of NH4Cl (50 mL) and extracted with ethyl acetate (50 mL x 3). The combined organic layer was dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure to get the title compound Vc as pale-yellow viscous oil; Yield: (3.25 g, 76%). 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 3.50-3.47 (m, 1H), 2.41 (s, 3H), 1.92-1.82 (m, 1H), 1.80-1.75 (m, 1H), 0.9- 0.86 (m, 1H), 0.61-0.55 (m, 2H), 0.25-0.23 (m, 1H), 0.18-0.14 (m, 1H). Step-4: 4-(cyclopropyl methyl)-5-methyl-1H-pyrazol-3-amine (Vd) [000108] To a stirred solution of 2-(cyclopropyl methyl)-3-oxobutanenitrile Vc (3.2 g, 0.0233 mol) in EtOH (50 mL) was added hydrazine hydrate (2.19 ml, 0.0349) and the reaction mixture was heated at 90 °C for 16 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled to rt and evaporated under reduced pressure. The residue obtained was diluted with NaHCO3 solution (50 mL) and extracted with ethyl acetate (50 mL x 3). The organic layer was dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure to get the title compound Vd. The crude product was taken for next step without further purification; Yield: (3.2 g, 91%). LC_MS Calculated for C8H13N3 is 151.11; Observed.152.20 [M++H]. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 3.80-3.60 (bs, 2H), 2.30 (d, J=5.6 Hz 3H), 1.70-1.50 (bs, 1H), 0.90-0.83 (m, 1H), 0.48-0.44 (m, 2H), 0.14-0.10 <semantics>(m,2H)<annotation encoding="application / x-tex">(m, 2H)< / annotation>< / semantics>. Step-5: 2-(Bis(methylthio) methylene) malononitrile (Ia) [000109] To a stirred solution of malononitrile (CAS:109-77-3, 5.0 g, 0.075 mol) in DMSO (50 ml) cooled to 0 °C was added K2CO3 (11.4 g, 0.0833 mol), CS2 (5.03 g, 0.0833 mol) and stirred at rt for 3 h. Then the reaction mixture cooled to 0 °C and methyl Iodide (9.4 ml, 0.1514 mol) was added and the reaction mixture was stirred at rt for 16 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was poured into ice cold water (50 ml) and the precipitate formed was filtered, washed with cold water and dried to get the compound Ia as brick red solid which was used in the next step without further purification; Yield: (6.2 g, 51%). Step-6: 7-amino-3-(cyclopropyl methyl)-2-methyl-5-(methylthio) pyrazolo[1,5-a] pyrimidine-6-carbonitrile (Ve) [000110] To a stirred solution of 2-(bis(methylthio)methylene) malononitrile Ia (3.3 g, 0.0198 mol) in pyridine (40 mL) was added 4-(cyclopropyl methyl)-5-methyl- 1H-pyrazol-3-amine Vd (3.0 g, 0.0198 mol) and the reaction mixture was heated at 120 °C for 16 h under N2 atmosphere. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled to rt and poured into ice cold water (50 mL). The precipitate formed was filtered, dried, and washed with cold mixture of ethyl acetate (10%) and n-hexane (90%) and dried under vacuo to afford the desired compound as a pale-yellow solid; Yield: (4.3 g, 80%). LC_MS Calculated for <semantics>C13H15N5S<annotation encoding="application / x-tex">C_{13}H_{15}N_5S< / annotation>< / semantics>: 273.10; Observed: 274.10 [M++H]. H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 6.26 (bs, 2II), 2.61-2.57 (m, 5II), 2.41 (s, 3II), 1.00-0.90 (bs, 1II), 0.45-0.43 (m, 2II), 0.24-0.22 (m, 2H). Step-7:7-amino-3-(cyclopropyl methyl)-2-methyl-5-(methyl sulfonyl) pyrazolo [1,5-a] pyrimidine-6-carbonitrile. (V) [000111] To a stirred solution of 7-amino-3-(cyclopropyl methyl)-2-methyl-5- (methylthio) pyrazolo[1,5-a] pyrimidine-6-carbonitrile Ve (2.3 g, 0.00842 mol) in DCM (50 mL) cooled to 0 °C, was slowly added m-CPBA (5.8 g, 0.0337 mol) and the reaction mixture was stirred at rt for 30 min. The progress of the reaction was monitored by TLC. After completion, the reaction was quenched with NaHCO3 (30) mL) and extracted with DCM (50 mL x 3). The combined organic layer was again given the saturated NaHCO3 (30 mL X 2) wash followed by with brine. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated under vacuo to afford the desired compound V as a pale-yellow solid; Yield: (2.1 g, 81%). LC_MS Calculated for <semantics>C13H15N5O2S<annotation encoding="application / x-tex">C_{13}H_{15}N_5O_2S< / annotation>< / semantics>: 305.09; Observed:306.10 [M++H]. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.00-6.60 (bs, 2H), 3.39 (s, 3H), 2.64 (d, J=6.8, 2H), 2.50 (s, 3H), 0.99-0.97 (bs, 1H), 0.49-0.46 (m, 2H), 0.24-0.22 (m, 2H). Synthesis of (6-methylpyridin-2-yl) methenamine. (VI) [Image disponible dans le document PDF, Image available in the PDF document] Step-1: 6-methylpicolinaldehyde. (VIa) [000112] To a solution of 2-bromo-6-methylpyridine (CAS: 5315-25-3, 5 g, 0.0290 mol) in Toluene (50 ml) was dropwise added n-BuLi (2.5M sol in THF, 11.62 ml, 0.0290 mol) at -78 °C. Reaction mixture was stirred for 1h at -78 °C. To this solution, DMF (2.69 ml, 0.0348 mol) was dropwise added at -78 °C. Reaction mixture was stirred for 1h at -50 °C followed by stirring for 30 min at 5-10 °C and at rt for 40 min. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled to 0 °C and quenched with saturated solution of NH4Cl (50 ml) and extracted with ethyl acetate (2x75 ml). The organic layer was washed with brine solution (50 ml) and dried with Na2SO4, filtered, and evaporated under reduced pressure to get crude material which was column purified using 60-120 silica get. Product was eluted with 5% ethyl acetate in hexane to afford compound VIa as pale- yellow liquid. Yield: (1.4g, 40%). LC-MS Calculated for C7H7NO: 121.15; Observe.122.15 [M++1]. 1HNMR (400 MHz, CDCl3): 8 10.054 (s, 1H), 7.745-7.799 <semantics>(m,2H),7.386−7.404(d,J=6.8Hz,1H),2.672(s,3H).<annotation encoding="application / x-tex">(m, 2H), 7.386-7.404 (d, J = 6.8 Hz, 1H), 2.672 (s, 3H).< / annotation>< / semantics> Step-2: (6-methylpyridin-2-yl) methenamine. (VI) [000113] To a stirred solution of 6-methylpicolinaldehyde VIa (1.4 g, 0.0115 mol) in Methanol (25 ml) was added Ammonium acetate (8.9 g, 0.115 mol) and the reaction mixture was stirred for 30 min at rt. Sodium cyanoborohydride (0.58g, 0.0092 mol) was then portion wise added and continued further stirring at rt for 10h. Progress of the reaction was monitored by TLC. After completion, solvent from reaction mass was removed under reduced pressure. The residue obtained was taken up with water (50 ml) and basified with aq. KOH. product was extracted with 5% MeOH in DCM (3x100 ml). Combined organic layer was dried over Na2SO4, filtered, and concentrated at reduced pressure to afford title compound VI as brown liquid. Yield: 1.2 g (85%). LC-MS Calculated for <semantics>C7H10N2<annotation encoding="application / x-tex">C_7H_{10}N_2< / annotation>< / semantics>: 122.08; Observed.123.08 [M++1]. 1HNMR (400) MHz, CDCl3): § 7.516-7.554 (t, <semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics> Hz, 1H), 7.091-7.072 (d, <semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics> Hz, 1H), <semantics>7.025−7.006<annotation encoding="application / x-tex">7.025-7.006< / annotation>< / semantics> (d, <semantics>J=7.6<annotation encoding="application / x-tex">J=7.6< / annotation>< / semantics> Hz, 1H), <semantics>3.935<annotation encoding="application / x-tex">3.935< / annotation>< / semantics> (s, 2H), <semantics>2.546<annotation encoding="application / x-tex">2.546< / annotation>< / semantics> (s, 3H). Synthesis of (6-ethylpyridin-2-yl) methenamine. (VII) [Image disponible dans le document PDF, Image available in the PDF document] Step-1: 6-((trimethylsilyl)ethynyl) picolinonitrile. (VIIa) [000114] To a stirred solution of 6-bromopicolinonitrile (CAS: 122918-25-6, 1.5 g, 0.008 mol) in TEA (0.060 mol) was added and it was purged under nitrogen. To this Trimethylsilyl acetylene (1.37 ml, 0.009 mol) followed by copper iodide (0.036 g, 0.0003 mol) was added and purging was continued further for 10 more minutes. After that Pd (PPh3)2Cl2 (0.089 g, 0.0001 mol) was added. Then the reaction mixture was stirred at room temperature for 30 minutes. The progress of the reaction was monitored by TLC. After completion, reaction mixture was filtered over Celite® bed and concentrated to get desired crude product VIIa. Yield: (1.2 g 75 %). LC MS Calculated for C11H12N2Si: 200.08; Observed: 201.15 [M++1]. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.824-7.784 (t, <semantics>J=8.4<annotation encoding="application / x-tex">J = 8.4< / annotation>< / semantics> Hz, 1H), 7.652-7.617 (t, <semantics>J=7.2<annotation encoding="application / x-tex">J = 7.2< / annotation>< / semantics> Hz, 2H), 0.287 (s, 9H). Step-2: 6-ethynylpicolinonitrile. (VIIb) [000115] To a stirred solution of 6-((trimethylsilyl)ethynyl) picolinonitrile VIIa (1.5 g, 0.005 mol) in MeOH (15 ml) cooled to 0 °C, was added K2CO3 (0.829 g, 0.005 mol) and the reaction mixture was stirred at 0 °C for 30 min. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was diluted with water (20 ml) and extracted with DCM (3x50 ml). The organic layer was dried with Na2SO4, filtered, and evaporated under reduced pressure. The crude material was purified by column chromatography by eluting with 20% ethyl acetate in hexane to yield the title compound VIIb as pale-yellow solid; Yield: (0.260 g, 34 %). LC MS Calculated for C8H4N2:128.04; Observed.: Not ionized. 1H NMR (400 MHz, CDCl3): <semantics>δ7.857−7.818<annotation encoding="application / x-tex">\delta 7.857 - 7.818< / annotation>< / semantics> (d, <semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics> Hz, 1H), <semantics>7.684−7.7.664<annotation encoding="application / x-tex">7.684 - 7.7.664< / annotation>< / semantics> (d, <semantics>J=8<annotation encoding="application / x-tex">J = 8< / annotation>< / semantics> Hz, 2H), <semantics>3.289<annotation encoding="application / x-tex">3.289< / annotation>< / semantics> (s, H). Step-3: (6-ethylpyridin-2-yl) methenamine. (VII) [000116] To a stirred solution of 6-ethynylpicolinonitrile VIIb (0.260 g, 0.00203 mol) in MeOH (3 ml) purged with N2 for 10 min, was added Pd / C (0.100 g) and the reaction mixture was stirred at rt for 24 h under H2 atmosphere. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was filtered through Celite® and the filtrate was concentrated. The crude material was purified by column chromatography by eluting with 20% ethyl acetate in hexane to yield the title compound VII as pale-yellow liquid; Yield: (0.100 g, 36%). LC MS Calculated for <semantics>C8H12N2<annotation encoding="application / x-tex">C_8H_{12}N_2< / annotation>< / semantics>: 136.10; Observed.: 137 [M++1]. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.583- <semantics>7.544(d,J=7.6Hz,1H),7.094−7.075(d,J=7.6Hz,1H),7.040−7.021(d,J=7.6Hz,1H)<annotation encoding="application / x-tex">7.544 (d, J = 7.6 Hz, 1H), 7.094-7.075 (d, J = 7.6 Hz, 1H), 7.040-7.021 (d, J = 7.6 Hz, 1H)< / annotation>< / semantics> 1H), 3.959 (s, 2H), 2.840-2.784 (q, <semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics> Hz, 2H), 1.322-1.255 (t, <semantics>J=8<annotation encoding="application / x-tex">J = 8< / annotation>< / semantics> Hz, 3H). Synthesis of N-methyl-1-(6-methylpyridin-2-yl) methenamine. (VIII) [Image disponible dans le document PDF, Image available in the PDF document] Step-1: (E)-N-methyl-1-(6-methylpyridin-2-yl) methenamine. (VIIIa) [000117] To a stirred solution of 6-methylpicolinaldehyde VIa (0.1 g, 0.000825) mol) in Methanol (5 ml) in molecular sieve was added methylamine (2 ml, 30% solution in methanol) and the resulting reaction mixture was stirred at rt for 16 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was filtered through the Celite® bed and evaporated under reduced pressure to get crude product VIIIa. The crude compound obtained was taken directly forward to the next step. Yield: (0.12 g, 100 %). Step-2: N-methyl-1-(6-methylpyridin-2-yl) methenamine. (VIII) [000118] To a stirred solution of (E)-N-methyl-1-(6-methylpyridin-2-yl) methenamine VIIIa (0.120 g, 0.00089 mol) in methanol (5 ml), was added sodium borohydride (0.051g, 0.00134 mol) at 0°C. Then the temp was allowed to reach room temperature and the reaction mixture was stirred at rt for 2 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was evaporated under reduced pressure and diluted with 10 ml water and extracted with 10% methanol in DCM (20 ml x 3). The organic layer was dried with Na2SO4, filtered, and evaporated under reduced pressure. The crude purified by manual column by eluted with 10% methanol in DCM product was eluted at 10% methanol in DCM to get the product VIII. Yield: <semantics>(0.123 g,101%)<annotation encoding="application / x-tex">(0.123 \text{ g}, 101\%)< / annotation>< / semantics>. LC MS Calculated. for <semantics>C8H12N2<annotation encoding="application / x-tex">C_8H_{12}N_2< / annotation>< / semantics>: 136.0; Observed: 137 [M++H]. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.647-7.608 (t, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics> = 8 Hz, 1H), <semantics>7.324−7.305<annotation encoding="application / x-tex">7.324-7.305< / annotation>< / semantics> (d, <semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics> Hz, 1H), <semantics>7.149−7.130<annotation encoding="application / x-tex">7.149-7.130< / annotation>< / semantics> (d, <semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics> Hz, 1H), <semantics>4.229<annotation encoding="application / x-tex">4.229< / annotation>< / semantics> (s, 2H), <semantics>2.730<annotation encoding="application / x-tex">2.730< / annotation>< / semantics> (s, 3H), 2.559 (s, 3H). Synthesis of 1-(6-methylpyridin-2-yl) propan-2-amine. (IX) [Image disponible dans le document PDF, Image available in the PDF document] Step-1: 1-(6-Methylpyridin-2-yl) propan-2-one. (IXa) [000119] To a stirred solution of 2,6-dimethylpyridine (CAS: 108-48-5, 5.0 g, 0.046 mol) in THF (65 ml) at -78°C was added n-BuLi (20.5 ml, 0.0512 mol) dropwise and stirred for 1h. Then N,N-Dimethylacetamide (4.1 ml. 0.0443 mol) was added slowly at -78°C and stirred at rt for 16 h. After completion (TLC), the reaction mixture was cooled to rt and quenched with 1.2 M HCl solution (25 ml) and stirred at rt for 30 min. Then, the reaction mixture was extracted with ethyl acetate (200 ml x 3). The organic layer was dried with Na2SO4, filtered, and evaporated under reduced pressure. The crude material was purified by flash column chromatography by eluting with 5% ethyl acetate in hexane to yield the title compound IXa as yellow liquid; Yield: (0.713) g, 10.2%). 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.54 (t, <semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics> Hz, 1H), 7.05 (d, <semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics> Hz, 1H), <semantics>7.00(d,J=8.0,Hz,1H)<annotation encoding="application / x-tex">7.00 (d, J = 8.0, Hz, 1H)< / annotation>< / semantics>, <semantics>3.89(s,2H)<annotation encoding="application / x-tex">3.89 (s, 2H)< / annotation>< / semantics>, <semantics>2.54(s,3H)<annotation encoding="application / x-tex">2.54 (s, 3H)< / annotation>< / semantics>, <semantics>2.22(s,3H)<annotation encoding="application / x-tex">2.22 (s, 3H)< / annotation>< / semantics>. Step-2: 1-(6-Methylpyridin-2-yl) propan-2-amine. (IX) [000120] To a stirred solution of 1-(6-methylpyridin-2-yl) propan-2-one IXa (0.713 g, 0.00475 mol) in MeOH (20 ml), was added ammonium acetate (3.7 g, 0.04753 mol) and stirred at room temperature for 30 min. Then NaCNBH3 (0.21 g, 0.003327 mol) was added portion-wise and the reaction mixture was stirred at room temperature for 16 h. Then the progress of the reaction was monitored by TLC. After completion, the reaction mixture was concentrated and diluted with saturated NaHCO3 solution (50 ml) and extracted with diethyl ether (50 ml x 3). The organic layer was dried with Na2SO4, filtered, and evaporated under reduced pressure the desired product IX as pale green liquid. This crude product obtained was taken for the next step without further purification; Yield: (0.43 g, 60%). 1H NMR (400 MHz, DMSO-d6): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.56 (t, <semantics>J=7.6 Hz,1H,7.04 (d, J=7.6 Hz,1H),7.00 (d, J=7.6,Hz,1H),3.21−3.18 (m, 1H),<annotation encoding="application / x-tex">J = 7.6 \text{ Hz}, 1\text{H}, 7.04 \text{ (d, } J = 7.6 \text{ Hz}, 1\text{H}), 7.00 \text{ (d, } J = 7.6, \text{Hz}, 1\text{H}), 3.21-3.18 \text{ (m, 1H)},< / annotation>< / semantics> <semantics>2.64 (dd, J=6.8 Hz, 2.4 Hz, 2H),2.42 (s, 3H),0.98 (dd, J=6.4 Hz, 2.4 Hz, 3H).<annotation encoding="application / x-tex">2.64 \text{ (dd, } J = 6.8 \text{ Hz, } 2.4 \text{ Hz, } 2\text{H)}, 2.42 \text{ (s, } 3\text{H)}, 0.98 \text{ (dd, } J = 6.4 \text{ Hz, } 2.4 \text{ Hz, } 3\text{H)}.< / annotation>< / semantics> Synthesis of 2-(6-(aminomethyl)pyridin-2-yl)propan-2-ol. (X) [Image disponible dans le document PDF, Image available in the PDF document] Step-1: Pyridine-2,6-dicarboxylic acid. (Xa) [000121] To a solution of 2,6-dimethylpyridine (CAS:108-48-5, 10 g, 0.17 mol) in 250 ml water, was slowly added 29.49 g of potassium permanganate (0.34 mol) with stirring. The mixture was refluxed until the purple color disappeared. Then, the mixture was cooled down to room temperature and another part of potassium permanganate (29.49 g, 0.34 mol) and water (150 ml) was slowly added. The mixture was refluxed at 100°C over 16 hrs. until the purple color disappeared again. The mixture was cooled down to room temperature. Filtration and removal of solvent until the residual volume down to 100 ml, then sulfuric acid (70%, 17.5 ml) was added slowly. The precipitate was filtered to afford pyridine-2,6-dicarboxylic acid Xa. Yield: (8.5 g, 55 %). LC MS Calculated for C7H5NO4: 167.02; Observed.:168.02 [M++1]. Step-2: dimethyl pyridine-2,6-dicarboxylate. (Xb) [000122] To a stirred solution of Pyridine-2,6-dicarboxylic acid Xa (8.5 g, 0.00598 mol) in methanol (1 L), added conc. sulphuric acid (4 ml) dropwise. The reaction mixture was refluxed at 60 °C for 16 hrs. After completion of reaction, removed the solvent by evaporation in vacuo, added water, the solid formed was filtered and dried to get the title compound Xb. Yield: (5 g, 51 %). LC_MS Calculated for C9H9NO4 is 195.05; Observed.: 196.15 [M++1]. 1H NMR (400 MHz, CDCl3): δ 8.338-8.314 (m, 2H), 8.055-8.013 (m, 1H), 4.036 (s, 6H). Step-3: methyl 6-(hydroxymethyl)picolinate. (Xc) [000123] Into a 500-ml round-bottom flask, was placed a solution of 2,6- dimethyl pyridine-2,6-dicarboxylate Xb (5g, 0.00487 mol) in a solvent mixture of methanol (174 ml) and dichloromethane (74 ml). NaBH4 (1.45 g, 0.00502 mol) was added to the reaction mixture in portions at 0°C. The resulting solution was stirred overnight at room temperature, and then it was quenched by the addition of Aq. NH4Cl (250 ml). The resulting solution was extracted with dichloromethane (2x200 ml) and the combined organic layers were dried over Na2SO4, filtered, and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate / petroleum ether (1:1) as eluent to yield methyl 6-(hydroxymethyl) pyridine-2-carboxylate Xc as white solid. Yield: (3.9 g, 93 %). LC MS Calculated. for C8H9NO3 is 167.16; Observed.: <semantics>168.20[M++1]<annotation encoding="application / x-tex">168.20 \, [M^++1]< / annotation>< / semantics>. 1H NMR (400 MHz, CDCl3): <semantics>δ8.048−8.029(d,J=7.6Hz,d)<annotation encoding="application / x-tex">\delta 8.048-8.029 \, (d, J=7.6Hz, d)< / annotation>< / semantics> 1H), 7.875-7.837 (t, J=7.6Hz, 1H), 7.541-7.522 (d, J=7.6Hz, 1H), 4.863 (s, 2H), 4.002 (s, 3H). Step-4: 2-(6-(hydroxymethyl) pyridin-2-yl) propan-2-ol. (Xd) [000124] To a stirred solution of methyl 6-(hydroxymethyl) picolinate Xc (3 g, 0.0179 mol) in diethyl ether (300 ml), added methyl magnesium bromide (3.4 M, 0.0358 mol, 10.5 ml) dropwise at 0 °C. Then the reaction mixture was stirred at room temperature for 3 hrs. After completion, the reaction mixture was quenched with NH4Cl and extracted with ethyl acetate (3x200 ml). The organic layer was dried with Na2SO4, filtered, and evaporated under reduced pressure. The crude material was purified by column chromatography by eluting with 30% ethyl acetate in hexane to yield the title compound as pale-yellow oil; Yield: (2.2 g, 73 %). LC MS Calc. for <semantics>C8H9NO3<annotation encoding="application / x-tex">C_8H_9NO_3< / annotation>< / semantics> is 167.16; Obs.: 168.20 [M++1]. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.735- 7.696 (t, <semantics>J=8<annotation encoding="application / x-tex">J = 8< / annotation>< / semantics> Hz, 1H), 7.333-7.313 (d, <semantics>J=8<annotation encoding="application / x-tex">J = 8< / annotation>< / semantics>Hz, 1H), 7.201-7.182 (d, <semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics> Hz, 1H), 4.783 (s, 2H), 4.412 (s, 1H), 3.190 (s, 1H), 1.566 (s, 6H). Step-5: 2-(6-(azidomethyl) pyridin-2-yl) propan-2-ol. (Xe) [000125] To a stirred solution of 2-(6-(hydroxymethyl) pyridin-2-yl) propan-2-ol Xd (0.4 g, 0.0832mol) in THF (5 ml), DPPA (0.0832 mol) at room temperature. The mixture was cooled to 0 °C and DBU (0.0832 mol) was added at rate such that the internal temperature did not exceed 20 °C. The reaction mixture was then warmed to 40 °C and stirred for 16 hrs. After completion, the reaction mixture was cooled to room temperature, added water (20 ml) and extracted with ethyl acetate (3x20 ml). The organic layer was dried with Na2SO4, filtered, and evaporated under reduced pressure. The crude material was purified by column chromatography by eluting with 10 % ethyl acetate in hexane to yield the title compound Xe as brown liquid; Yield: (0.26 g, 57%). LC MS Calculated for C9H12N4O is 192.10; Observed.: 193.10 [M++1]. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.743-7.724 (t, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics> = 7.6 Hz, 1H), 7.337-7.317 (d, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics> = 8 Hz, 1H), <semantics>7.245−7.226<annotation encoding="application / x-tex">7.245-7.226< / annotation>< / semantics> (d, <semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics> Hz, 1H), <semantics>4.905<annotation encoding="application / x-tex">4.905< / annotation>< / semantics> (s, 1H), <semantics>4.465<annotation encoding="application / x-tex">4.465< / annotation>< / semantics> (s, 2H), <semantics>1.550<annotation encoding="application / x-tex">1.550< / annotation>< / semantics> (s, 6H). Step-6: 2-(6-(aminomethyl) pyridin-2-yl) propan-2-ol. (X) [000126] To a stirred solution of 2-(6-(azidomethyl) pyridin-2-yl) propan-2-ol Xe (0.26 g) in methanol (10 ml), added Pd / C (100 mg) at room temperature. The reaction was stirred at same temperature for 1 hr under hydrogen. After completion, the reaction mixture was filtered through Celite® bed, and the bed was washed with methanol. The filtrate was concentrated under reduced pressure to get the title compound X as brown liquid; Yield: (0.3 g, crude). The crude product obtained was taken for the next step without further purification. Synthesis of 2-(5-methylpyridin-2-yl)ethan-1-amine. (XI) [Image disponible dans le document PDF, Image available in the PDF document] Step-1: 2-(5-Methylpyridin-2-yl) acetonitrile. (XIa) [000127] To a stirred solution of n-BuLi (14 ml, 0.034 mol) in THF (75 ml) was added ACN (1.75 ml, 0.0388 mol) at -78°C and stirred for 1h. Then added 2-bromo- 5-methylpyridine (CAS: 3510-66-5, 1.67 g, 0.0097 mol) slowly and stirred at rt for 2 h. After completion (TLC), the reaction mixture was diluted with ice cold water (50 ml) and extracted with ethyl acetate (50 ml x 3). The organic layer was dried over Na2SO4, filtered, and evaporated under reduced pressure to get the desired product Xia Yield: (0.6 g, crude). The crude product was taken for the next step without further purification. Step-2: 2-(5-Methylpyridin-2-yl) ethan-1-amine. (XI) [000128] To a stirred solution of 2-(5-methylpyridin-2-yl) acetonitrile XIa (0.6 g, 0.0045 mol) in THF (100 ml) was added BH3-Me2S, (10 ml, 0.0020 mol) at room temperature and stirred for 2 h at 70 °C. After completion (TLC), the reaction mixture cooled to room temperature, then added MeOH (5ml) and 10ml 1N HCl and the aqueous layer washed with ethyl acetate separated the layer and the aqueous layer basified with 1N NaOH and extracted with DCM (100ml x 3). The organic layer was dried with Na2SO4, filtered and evaporated under reduced pressure to give title compound XI, the crude product was taken for the next step without purification; Yield: (0.2 g, 32%). LC MS Calculated for C8H12N2 is 136.10; Observed.137.2 [M++H]. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 8.35 (s, 1H), 7.42 (d, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics> = 7.6 Hz 1H), 7.06 <semantics>(d,J=8.0 Hz 1H),3.12(t,J=6.4 Hz,2H),2.91(d,J=6.4 Hz,2H),2.3(s,3H).<annotation encoding="application / x-tex">(d, J = 8.0 \text{ Hz 1H}), 3.12 (t, J = 6.4 \text{ Hz}, 2\text{H}), 2.91 (d, J = 6.4 \text{ Hz}, 2\text{H}), 2.3 (s, 3\text{H}).< / annotation>< / semantics> Synthesis of 2-(5-fluoropyridin-2-yl)ethan-1-amine. (XII) [Image disponible dans le document PDF, Image available in the PDF document] Step-1: 5-Fluoropicolinaldehyde. (XIIa) [000129] To a stirred solution of 2-bromo-5-fluoropyridine (CAS: 41404-58-4, 2.69 g, 0.0147 mol) in toluene (30 ml) at -78°C was added n-BuLi (5.9 ml, 0.0147 mol) dropwise and stirred for 1h. Then DMF (1.36 ml) and added slowly at -50°C and stirred for 30 min. After completion (TLC), the reaction mixture was quenched with MeOH (30 ml) and stirred at 5-10 °C for 30 min. Then, NH4Cl solution (75 ml) was added and stirred at rt for 40 min and then extracted with ethyl acetate (100 ml x 3). The organic layer was dried with Na2SO4, filtered, and evaporated under reduced pressure. The crude material was purified by flash column chromatography by eluting with 5% ethyl acetate in hexane to yield the title compound XIIa as yellow liquid; Yield: (1.01 g, 54.89%). LC MS Calculated for C6H4FNO is 125.03; Observed.126.00 [M++H]. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 10.04 (s,1H), 8.63 (d, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics> = <semantics>2.0 Hz<annotation encoding="application / x-tex">2.0 \text{ Hz}< / annotation>< / semantics>, <semantics>1H<annotation encoding="application / x-tex">1\text{H}< / annotation>< / semantics>), <semantics>8.05−8.02 (m, 1H)<annotation encoding="application / x-tex">8.05-8.02 \text{ (m, 1H)}< / annotation>< / semantics>, <semantics>7.58 (dt, J=8.4 Hz<annotation encoding="application / x-tex">7.58 \text{ (dt, } J = 8.4 \text{ Hz}< / annotation>< / semantics>, <semantics>2.8 Hz<annotation encoding="application / x-tex">2.8 \text{ Hz}< / annotation>< / semantics>, <semantics>1H<annotation encoding="application / x-tex">1\text{H}< / annotation>< / semantics>). Step-2: (E)-5-Fluoro-2-(2-nitrovinyl) pyridine. (XIIb) [000130] To a stirred solution of 5-fluoropicolinaldehyde XIIa (1.01 g, 0.00807) mol) in DCM (20 ml), was added TEA (2.24 ml, 0.0161 mol) and nitromethane (0.52 ml, 0.00968 mol) and the reaction mixture was stirred at rt for 2 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was evaporated under reduced pressure. The crude material was dissolved in DCM (20 ml) and treated with TEA (1.77 ml, 0.0242 mol) and MsCl (2.75 ml, 0.0242 mol) at 0 °C and the reaction mixture was stirred at rt for 20 min. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was evaporated under reduced pressure. And the crude was purified by column chromatography by eluting with 10% ethyl acetate in hexane to yield the title compound XIIb as green solid; Yield: (1.2 g, 88.8%). LC MS Calculated for C7H5FN2O2 is 168.03; Observed.169.00 [M++H]. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 8.54 (s,1H), 7.93 (q, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics> = 12.8 Hz, 2H), 7.50- 7.49 (m, 2H). Step-3: 2-(5-Fluoropyridin-2-yl) ethan-1-amine. (XII) [000131] To a stirred solution of (E)-5-fluoro-2-(2-nitrovinyl) pyridine XIIb (1.2 g, 0.0071 mol) in THF (50 ml), was added LAH (1M sol in THF, 21.4 ml, 0.024 mol) at -20 °C dropwise. Then the temp was allowed to reach to rt, and the reaction mixture was stirred at rt for 2 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled to 0 °C and quenched with saturated Na2SO4 solution (50 ml) and extracted with ethyl acetate (50 ml x 3). The organic layer was dried with Na2SO4, filtered, and evaporated under reduced pressure. The crude was purified by column chromatography by eluting with 10% methanolic NH3 in DCM to yield the title compound as pale green liquid; Yield: (0.35 g, 35%). LC MS Calculated for C7H9FN2 is 140.07; Observed.141.2 [M++H]. 1H NMR (400 MHz, DMSO-d6): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 8.45 (d, <semantics>J=3.2<annotation encoding="application / x-tex">J = 3.2< / annotation>< / semantics> Hz, 1H), 7.62 (dd, <semantics>J=8.4<annotation encoding="application / x-tex">J = 8.4< / annotation>< / semantics> Hz, 2.8 Hz, 1H), 7.34-7.31 (m, 1H), 2.88 (t, <semantics>J=6.4<annotation encoding="application / x-tex">J = 6.4< / annotation>< / semantics> Hz, 2H), 2.81 (d, <semantics>J=6.4<annotation encoding="application / x-tex">J = 6.4< / annotation>< / semantics> Hz, 2H), 2.5 (bs, 2H). Synthesis of 2-(6-methoxypyridin-2-yl) ethan-1-amine. (XIII) [Image disponible dans le document PDF, Image available in the PDF document] Step-1: (E)-6-Methoxy-2-(2-nitrovinyl) pyridine. (XIIIa) [000132] To a stirred solution of 6-methoxypicolinaldehyde (CAS:54221-96-4, 1.0 g, 0.00724 mol) in DCM (20 ml), was added TEA (2.19 g, 0.0217 mol) and nitromethane (1.32 g, 0.0216 mol) and the reaction mixture was stirred at rt for 2 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was evaporated under reduced pressure. The crude material was dissolved in DCM (20 ml) and treated with TEA (2.19 g, 0.0217 mol) and mesyl chloride (2.47 g, 0.0217 mol) at 0 °C and the reaction mixture was stirred at rt for 30 min. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was evaporated under reduced pressure. And the crude was purified by column chromatography by eluting with 7% ethyl acetate in hexane to yield the title compound XIIa as yellow solid; Yield: (0.8 g, 80%). 1H NMR (400 MHz, CDCl3): δ8.016-7.983 <semantics>(d,J=13.2 Hz,1H),7.845−7.812(d,J=13.2 Hz,1H),7.652−7.614(t,J=8Hz,1H),<annotation encoding="application / x-tex">(d, J = 13.2 \text{ Hz}, 1\text{H}), 7.845 - 7.812 (d, J = 13.2 \text{ Hz}, 1\text{H}), 7.652 - 7.614 (t, J = 8\text{Hz}, 1\text{H}),< / annotation>< / semantics> <semantics>7.069−7.052<annotation encoding="application / x-tex">7.069-7.052< / annotation>< / semantics> (d, <semantics>J=6.8<annotation encoding="application / x-tex">J = 6.8< / annotation>< / semantics> Hz, 1H), <semantics>6.863−6.843<annotation encoding="application / x-tex">6.863-6.843< / annotation>< / semantics> (d, <semantics>J=8<annotation encoding="application / x-tex">J = 8< / annotation>< / semantics>Hz, 1H), <semantics>3.969<annotation encoding="application / x-tex">3.969< / annotation>< / semantics> (s, 3H). Step-2: 2-(6-Methoxypyridin-2-yl) ethan-1-amine. (XIII) [000133] To a stirred solution of (E)-6-methoxy-2-(2-nitrovinyl) pyridine 2 (0.8) g, 0.0044 mol) in DEE (16 ml), was added LAH (1M sol in THF, 13.3 ml, 0.0133 mol) at -10 °C dropwise. Then the temp was allowed to reach to rt and the reaction mixture was stirred at rt for 2 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled to 0 °C and quenched with chilled water (10 ml), 15N aq. NaOH (1 ml), and extracted with 10% methanol in DCM (20 ml x 3). The organic layer was dried with Na2SO4, filtered, and evaporated under reduced pressure to give crude product XIII as brown liquid. The crude product was carried forward to next step without purification; Yield: (0.43 g, 63%). LC MS Calculated for C8H12N2O: 152; Observe.153 [M++H]. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.477 (d, 1H), 6.733-6.726 (d, J=2.8Hz, 1H), 6.570-6.560 (m, 2H), 3.918 (s, 3H), 3.108 (t, 2H), 2.820 (t, 2H). Synthesis of 2-(6-methylpyridin-2-yl) ethan-1-amine. (XIV) [Image disponible dans le document PDF, Image available in the PDF document] Step-1. (E)-6-Methoxy-2-(2-nitrovinyl) pyridine. (XVa) [000134] To a stirred solution of 6-methylpicolinaldehyde Via (8.0 g, 0.0660) mol) in DCM (80 ml), was added TEA (13.36 g, 0.132 mol) and nitromethane (5.15 g, 0.079 mol) and the reaction mixture was stirred at rt for 2 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was evaporated under reduced pressure. The crude material was dissolved in DCM (80 ml) and treated with TEA (20.03 g, 0.198 mol) and mesyl chloride (22.58 g, 0.198 mol) at 0 °C and the reaction mixture was stirred at rt for 30 min. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was evaporated under reduced pressure. And the crude was purified by column chromatography by eluting with 7-10% ethyl acetate in hexane to yield the title compound XVa as brown liquid; Yield: (9 g, 83.33%). 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>8.076-8.042 (d, J=13.6Hz, 1H), 7.942-7.910 (d, J=12.8Hz, 1H), 7.722-7.605 (t, J=7.2Hz, 1H), 7.331-7.314 (d, J=6.8Hz, 1H), 7.278-7.7.266 (d, J=4.8Hz, 1H), 2.263 (s, 3H). Step-3: 2-(6-methylpyridin-2-yl) ethan-1-amine (XIV) [000135] To a stirred solution of (E)-6-methoxy-2-(2-nitrovinyl) pyridine 2 (9.18) g, 0.0559 mol) in DEE (700 ml), was added LAH (1M sol in THF, 224 ml, 0.22 mol) at 0 °C dropwise. Then the temp was raised to 40 °C and continued for 2 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled to 0 °C and quenched with chilled water (50 ml), 15N aq. NaOH (5 ml), and filtered through Celite® bed. Celite®bed was washed with DEE (250 ml). DEE from filtrate was distilled off at reduced pressure to get title compound XIV brown liquid which was used for next step without further purification. Yield: (5.09 g, 67%). LC MS Calculated. for C8H12N2: 136; Observed.137 [M++H]. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.577-7.539 (t, <semantics>J=8<annotation encoding="application / x-tex">J = 8< / annotation>< / semantics> Hz, 1H), 7.050-7.012 (m, 2H), 2.867-2.807 (t, <semantics>J=6.8<annotation encoding="application / x-tex">J = 6.8< / annotation>< / semantics> Hz, 2H), <semantics>2.771−2.750<annotation encoding="application / x-tex">2.771-2.750< / annotation>< / semantics> (t, <semantics>J=8.4<annotation encoding="application / x-tex">J = 8.4< / annotation>< / semantics> Hz, 2H), <semantics>2.420<annotation encoding="application / x-tex">2.420< / annotation>< / semantics> (s, 3H). Synthesis of 2-(6-(2-aminoethyl) pyridin-2-yl)propan-2-ol.(XV) [Image disponible dans le document PDF, Image available in the PDF document] Step-1: 6-(2-hydroxypropan-2-yl) picolinaldehyde (XVa) [000136] To a stirred solution of 2-(6-(hydroxymethyl) pyridin-2-yl) propan-2- ol Xd (1.8 g, 0.0107 mol) in DCM (50 ml), added DMP (6.85 g, 0.0161 mol) portion wise at 0 °C. And the reaction mixture was stirred at same temperature for 30 min. The reaction was monitored by TLC. After completion, the reaction mixture was quenched with aq. Sodium bicarbonate (50 ml) and extracted by DCM (100 ml x 3 times). The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. Crude compound was purified by column chromatography, the product was eluted at 10% ethyl acetate / Hexane to afford title compound XVa as pale-yellow oil. Yield: (1.1g, 62%). 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 10.094 (s, 1H), 7.929-7.870 (m, 2H), 7.659-7.641 (d, J=7.2Hz, 1H), 4.606 (bs, 1H), 1.607 (s, 6H). Step-2: (E)-2-(6-(2-nitrovinyl) pyridin-2-yl) propan-2-ol (XVb) [000137] To a stirred solution of 6-(2-hydroxypropan-2-yl) picolinaldehyde XVa (0.5 g, 0.00303 mol) in DCM (5 ml), was added TEA (0.613 g, 0.00606 mol) and nitromethane (0.1 g, 0.0016 mol) and the reaction mixture was stirred at rt for 2 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was evaporated under reduced pressure. The crude material was dissolved in DCM (20) ml) and treated with TEA (0.67 g, 0.00663 mol) and mesyl chloride (0.756 g, 0.00663 mol) at 0 °C and the reaction mixture was stirred at rt for 30 min. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was evaporated under reduced pressure. And the crude was purified by column chromatography by eluting with 7% ethyl acetate in hexane to yield the title compound XVb as yellow solid; Yield: (0.35 g, 76%). LC MS Calculated for C10H12N2O3: 208.08; Observed:209.20 [M++H]. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 8.036-8.003 (d, J=13.2Hz, 1H), 7.951-7.918 (d, J=13.2Hz, 1H), 7.841-7.801 (t, J=8Hz, 1H), 7.531- 7.510 (d, J=8.4Hz, 1H), 7.406-7.388 (d, J= 7.2Hz, 1H), 1.577 (s, 6H). Step-3: 2-(6-(2-aminoethyl) pyridin-2-yl) propan-2-ol (XV) [000138] To a stirred solution of (E)-1-Methyl-3-(2-nitrovinyl)-1H-pyrazole 3 (0.55 g,0.00264 mol) in diethyl ether (26 ml), was added LAH (1M solution in THF, 0.401g, 0.0106 mol) at 0 °C dropwise. Then the temp was allowed to reach to rt and the reaction mixture was stirred at 40 °C for 3 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled to 0 °C and quenched with chilled water (3 ml), 15N aq. NaOH (2 ml). Inorganic salts were filtered and washed with DEE (25 ml). Solvent from filtrate were concentrated under reduced pressure to afford crude compound XV which was used for next step without further purification. Yield: (0.3g, 63%). 1H NMR (400 MHz, DMSO-d6): δ 7.666-7.628 (t, J=7.2Hz, 1H), 7.450-7.432 (d, J=7.2Hz, 1H), 7.069-7.050 (d, J=7.6Hz, 1H), 2.886- 2.870 (t, J=6.4Hz, 2H), 2.784-2.766 (t, J=7.2Hz, 2H), 1.414 (s, 6H). Synthesis of 2-(1-ethyl-1H-pyrazol-3-yl) ethan-1-amine. (XVI) [Image disponible dans le document PDF, Image available in the PDF document] Step-1: 1-ethyl-1H-pyrazole-3-carbaldehyde (XVIa) [000139] To a stirred solution of 1H-pyrazole-3-carbaldehyde (CAS: 3920-50-1, 3 g, 0.031 mol) in DMF (20 ml) was added Potassium carbonate (10 g, 0.0723 mol) and Ethyl iodide (5.8 g, 0.0374 mol) and the reaction mixture was stirred at rt for 16 h. The progress of the reaction was monitored by TLC. After completion, water (30) ml) was added and extracted with ethyl acetate (3x30 ml). Combined ethyl acetate layer was washed with 10% brine solution (50 ml). Organic layer was dried over sodium sulphate, filtered, and concentrated to afford crude1-ethyl-1H-pyrazole-3- carbaldehyde which was further purified by column chromatography using 30% ethyl acetate in hexane to afford title compound XVI as yellow colored liquid. Yield: (2.4) g, 63 %). 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 9.982 (s, 1H), 7.467-7.462 (d, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics> = 2Hz, 1H), <semantics>6.808−6.802<annotation encoding="application / x-tex">6.808-6.802< / annotation>< / semantics> (d, <semantics>J=2.4<annotation encoding="application / x-tex">J = 2.4< / annotation>< / semantics> Hz, 1H), <semantics>4.307−4.252<annotation encoding="application / x-tex">4.307-4.252< / annotation>< / semantics> (q, <semantics>J=7.2<annotation encoding="application / x-tex">J = 7.2< / annotation>< / semantics> Hz, 2H), <semantics>1.572−1.536<annotation encoding="application / x-tex">1.572-1.536< / annotation>< / semantics> (t, <semantics>J=<annotation encoding="application / x-tex">J =< / annotation>< / semantics> 7.2 Hz, 3H). Step-2: (E)-1-ethyl-3-(2-nitrovinyl)-1H-pyrazole (XVIb) [000140] To a stirred solution of 1-ethyl-1H-pyrazole-3-carbaldehyde 2 (2.4 g, 0.0193 mol) in nitromethane (22 ml) was added Ammonium acetate (2.3 g, 0.029 mol) and the reaction mixture was stirred for 1h at 100 °C. Progress of reaction was monitored by TLC. After completion, solvent from reaction mass was removed under reduced pressure. Residue was taken up with water (50 ml) and extracted with ethyl acetate (3x35 ml). Combined ethyl acetate layer was washed with 10% brine solution (35 ml). Organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to get the desired product XVIb. The crude product was carried forward to next step without further purification. Yield: (1.6 g, 49 %). 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.990-7.956 (d, <semantics>J=13.6<annotation encoding="application / x-tex">J = 13.6< / annotation>< / semantics> Hz, 1H), 7.637-7.604 (d, <semantics>J=13.2<annotation encoding="application / x-tex">J = 13.2< / annotation>< / semantics> Hz, 1H), 7.450- 7.446 (d, <semantics>J=1.6<annotation encoding="application / x-tex">J = 1.6< / annotation>< / semantics> Hz, 1H), 6.542-6.538 (d, <semantics>J=1.6<annotation encoding="application / x-tex">J = 1.6< / annotation>< / semantics> Hz, 1H), 4.253-4.190 (q, <semantics>J=7.2<annotation encoding="application / x-tex">J = 7.2< / annotation>< / semantics> Hz, 2H), <semantics>1.543−1.506<annotation encoding="application / x-tex">1.543-1.506< / annotation>< / semantics> (t, <semantics>J=7.2<annotation encoding="application / x-tex">J=7.2< / annotation>< / semantics> Hz, 3H). Step-3: 2-(1-ethyl-1H-pyrazol-3-yl) ethan-1-amine (XVI) [000141] To a stirred solution of (E)-1-ethyl-3-(2-nitrovinyl)-1H-pyrazole 3 (1.5) g, 0.0089 mol) in DEE (60 ml), was added LAH (1M sol in THF, 36 ml, 0.036 mol) at 0 °C dropwise. Then the temp was allowed to reach to rt and the reaction mixture was stirred at 40°C for 3 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled to 0 °C and quenched with chilled water (2 ml), 15N aq. NaOH (1 ml). Inorganic salts were filtered and washed with DEE (25 ml). Solvent from filtrate were concentrated under reduced pressure to afford crude compound XVI which was used for next step without further purification. Yield: (1 g, 81 %). 1H NMR (400 MHz, CDCl3): δ 7.312 (d, 1H), 6.054-6.050 (d, 1H), 4.150- <semantics>4.096<annotation encoding="application / x-tex">4.096< / annotation>< / semantics> (q, <semantics>J=7.2<annotation encoding="application / x-tex">J = 7.2< / annotation>< / semantics> Hz, 2H), <semantics>3.008−2.974<annotation encoding="application / x-tex">3.008-2.974< / annotation>< / semantics> (t, 2H), <semantics>2.787−2.754<annotation encoding="application / x-tex">2.787-2.754< / annotation>< / semantics> (t, 2H), <semantics>1.483−1.432<annotation encoding="application / x-tex">1.483-1.432< / annotation>< / semantics> (t, <semantics>J=<annotation encoding="application / x-tex">J =< / annotation>< / semantics> 7.2 Hz, 3H). Synthesis of 2-(1-ethyl-1H-pyrazol-3-yl)ethan-1-amine. (XVII) [Image disponible dans le document PDF, Image available in the PDF document] Step-1: 1-methyl-1H-pyrazole-3-carbaldehyde (XVIIa) [000142] To a stirred solution of 1H-pyrazole-3-carbaldehyde (CAS: 3920-50- 1,5 g,0.052 mol) in DMF (25 ml) was added Potassium carbonate (17.97 g,0.13 mol) and Methyl iodide (8.86 g, 0.0624 mol) and the reaction mixture was stirred at room temperature for 16 h. The progress of the reaction was monitored by TLC. After completion, water (50 ml) was added and extracted with ethyl acetate (3x50 ml). Combined ethyl acetate layer was washed with 10% brine solution (50 ml). Organic layer was dried over sodium sulphate, filtered, and concentrated to afford crude 1- Methyl-1H-pyrazole-3-carbaldehyde, which was further purified by column chromatography using 30% ethyl acetate in hexane to afford title compound XVIIa as yellow colored liquid. Yield: (2.6 g, 45%). 1H NMR (400 MHz, CDCl3): δ 9.960 (s, 1H), <semantics>7.431−7.427<annotation encoding="application / x-tex">7.431-7.427< / annotation>< / semantics> (d, <semantics>J=1.6<annotation encoding="application / x-tex">J = 1.6< / annotation>< / semantics> Hz, 1H), <semantics>6.812−6.805<annotation encoding="application / x-tex">6.812-6.805< / annotation>< / semantics> (d, <semantics>J=2.8<annotation encoding="application / x-tex">J = 2.8< / annotation>< / semantics> Hz, 1H), <semantics>4.020<annotation encoding="application / x-tex">4.020< / annotation>< / semantics> (s, 1H). Step-2: (E)-1-methyl-3-(2-nitrovinyl)-1H-pyrazole (XVIIb) [000143] To a stirred solution of 1-Methyl-1H-pyrazole-3-carbaldehyde XVIIa (2.4 g, 0.020 mol) in nitromethane (43 ml) was added ammonium acetate (2.5 g, 0.031 mol) and the reaction mixture was stirred for 1h at 100 °C. Then the progress of reaction was monitored by TLC. After completion, solvent from reaction mass was removed under reduced pressure. Residue was taken up with water (50 ml) and extracted with ethyl acetate (3x50 ml). Combined ethyl acetate layer was washed with 10% brine solution (50 ml). Organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. Crude product was purified by column chromatography using 20% ethyl acetate in hexane to afford pure title compound XVIIb. Yield: (1.4 g, 49 %). 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>7.970-7.936 (d, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics> = 13.6 Hz, 1H), 7.631-7.598 (d, <semantics>J=13.2<annotation encoding="application / x-tex">J = 13.2< / annotation>< / semantics> Hz, 1H), 7.428-7.422 (d, <semantics>J=2.4<annotation encoding="application / x-tex">J = 2.4< / annotation>< / semantics> Hz, 1H), 6.549- <semantics>6.543<annotation encoding="application / x-tex">6.543< / annotation>< / semantics> (d, <semantics>J=2.4<annotation encoding="application / x-tex">J = 2.4< / annotation>< / semantics> Hz, 1H), <semantics>3.971<annotation encoding="application / x-tex">3.971< / annotation>< / semantics> (s, 3H). Step-3: 2-(1-Methyl-1H-pyrazol-3-yl) ethan-1-amine (XVII) [000144] To a stirred solution of (E)-1-Methyl-3-(2-nitrovinyl)-1H-pyrazole 3 (1.4 g, 0.009 mol) in DEE (60 ml), was added LAH (1M solution in THF, 29 ml, 0.029 mol) at 0 °C dropwise. Then the temp was allowed to reach to rt and the reaction mixture was stirred at 40 °C for 3 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled to 0 °C and quenched with chilled water (2 ml), 15N aq. NaOH (1 ml). Inorganic salts were filtered and washed with DEE (25 ml). Solvent from filtrate were concentrated under reduced pressure to afford crude compound XVII which was used for next step without further purification. Yield: (1 g, 87%). 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.278-7.268 (d, <semantics>J=<annotation encoding="application / x-tex">J =< / annotation>< / semantics> 4Hz, 1H), <semantics>6.053−6.050<annotation encoding="application / x-tex">6.053-6.050< / annotation>< / semantics> (d, <semantics>J=1.2<annotation encoding="application / x-tex">J = 1.2< / annotation>< / semantics> Hz, H), <semantics>3.853<annotation encoding="application / x-tex">3.853< / annotation>< / semantics> (s, 3H), <semantics>3.008−2.969<annotation encoding="application / x-tex">3.008-2.969< / annotation>< / semantics> (t, <semantics>J=6.8<annotation encoding="application / x-tex">J = 6.8< / annotation>< / semantics> Hz, 2H), <semantics>2.778−2.745<annotation encoding="application / x-tex">2.778-2.745< / annotation>< / semantics> (t, <semantics>J=6.8<annotation encoding="application / x-tex">J = 6.8< / annotation>< / semantics> Hz, 2H). Synthesis of 2-(3-(2-aminoethyl)-1H-pyrazol-1-yl)-2-methylpropan-1-ol. XVIII [Image disponible dans le document PDF, Image available in the PDF document] Step-1: Ethyl 2-(3-formyl-1H-pyrazol-1-yl)-2-methylpropanoate (XVIIIa) [000145] To a stirred solution of 1H-pyrazole-3-carbaldehyde (CAS: 3920-50-1, 1 g,0.01 mol) in DMF (5 ml) was added Potassium carbonate (3 g, 0.02 mol) and ethyl 2-bromo-2-methylpropanoate (2 g, 0.01 mol) and the reaction mixture was stirred at room temperature for 16 h. Then the progress of the reaction was monitored by TLC. After completion, water (25 ml) was added and extracted with ethyl acetate (3x25 ml). Combined ethyl acetate layer was washed with 10% brine solution (25 ml). Organic layer was dried over sodium sulphate, filtered, and concentrated to afford crud compound which was further purified by column chromatography using 30% ethyl acetate in hexane to afford title compound XVIIIa. Yield: (1.8 g, 82%). LC MS Calculated for <semantics>C10H14N2O3<annotation encoding="application / x-tex">C_{10}H_{14}N_2O_3< / annotation>< / semantics> is 210.06; Observed.: 211.20 [M++1]. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 9.980 (s, 1H), 7.623 (s, 1H), 6.836 (s, 1H), 4.217-4.164 (q, <semantics>J=7.2<annotation encoding="application / x-tex">J = 7.2< / annotation>< / semantics> Hz, 2H), <semantics>1.999<annotation encoding="application / x-tex">1.999< / annotation>< / semantics> (s, 6H), <semantics>1.235−1.200<annotation encoding="application / x-tex">1.235-1.200< / annotation>< / semantics> (t, <semantics>J=6.8<annotation encoding="application / x-tex">J = 6.8< / annotation>< / semantics> Hz, 3H). Step-2: ethyl (E)-2-methyl-2-(3-(2-nitrovinyl)-1H-pyrazol-1-yl) propanoate (XVIIIb) [000146] To a stirred solution of ethyl 2-(3-formyl-1H-pyrazol-1-yl)-2- methylpropanoate XVIIIa (1.8 g,0.008 mol) in nitromethane (17 ml) was added Ammonium acetate (0.99 g, 0.0121 mol) and the reaction mixture was stirred for 1h at 100 °C. Progress of reaction was monitored by TLC. After completion, solvent from reaction mass was removed under reduced pressure. Crude product was purified by column chromatography using 20% ethyl acetate in hexane to afford pure title compound XVIIIb. Yield: (0.55 g, 25%). LC MS Calculated for C11H15N3O4 is 253.11; Observed.: 254.20 [M++1]. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 8.007-7.973 (d, <semantics>J=13.6 Hz,1H,7.629−7.611(m,2H),7.509−7.504(d,<math>J=2 Hz,1H),6.580−6.574(d,3.680)<annotation encoding="application / x-tex">J = 13.6 \text{ Hz}, 1\text{H}, 7.629-7.611 (m, 2\text{H}), 7.509-7.504 (d, J = 2 \text{ Hz}, 1\text{H}), 6.580-6.574 (d, 3.680)< / annotation>< / semantics> <semantics>J=2.4 Hz,1H,4.210−4.120(q,J=7.6 Hz,2H),1.187(s,6H),1.237−1.163(t,J=7.6 Hz)<annotation encoding="application / x-tex">J = 2.4 \text{ Hz}, 1\text{H}, 4.210-4.120 (q, J = 7.6 \text{ Hz}, 2\text{H}), 1.187 (s, 6\text{H}), 1.237-1.163 (t, J = 7.6 \text{ Hz})< / annotation>< / semantics> Hz, 3H). Step-3: 2-(3-(2-aminoethyl)-1H-pyrazol-1-yl)-2-methylpropan-1-ol (XVIII) [000147] To a stirred solution of ethyl (E)-2-methyl-2-(3-(2-nitrovinyl)-1H- pyrazol-1-yl) propanoate 4 (0.55 g, 0.0021 mol) in DEE (15 ml), was added LAH (1M solution in THF, 8.7 ml, 0.0086 mol) at 0 °C dropwise. Then the temp was allowed to reach to rt and the reaction mixture was stirred at 40 °C for 3 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled to 0 °C and quenched with chilled water (2 ml), 15N aq. NaOH (1 ml). Inorganic salts were filtered and washed with DEE (25 ml). Solvent from filtrate were concentrated under reduced pressure to afford crude compound XVIII which was used for next step without further purification. Yield: (0.35 g, 88%). LC MS Calculate for C9H17N3O is 183.14; Observe.: 184.30 [M++1]. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.449 (s, 2H), <semantics>6.071<annotation encoding="application / x-tex">6.071< / annotation>< / semantics> (s, 1H), <semantics>3.76<annotation encoding="application / x-tex">3.76< / annotation>< / semantics> (s, 2H), <semantics>2.999−2.968<annotation encoding="application / x-tex">2.999-2.968< / annotation>< / semantics> (t, <semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics> Hz, 2H), <semantics>2.811−2.740<annotation encoding="application / x-tex">2.811-2.740< / annotation>< / semantics> (t, <semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics> Hz, 2H), 1.596 (s, 6H). Synthesis of 2-(5-methoxypyridin-2-yl)ethan-1-amine. XIX [Image disponible dans le document PDF, Image available in the PDF document] Step-1: (E)-5-Methoxy-2-(2-nitrovinyl) pyridine (XIXa) [000148] To a stirred solution of 5-methoxypicolinal dehyde 1 (2.0 g, 0.0145 mol) in DCM (20 ml), was added TEA (4.04 ml, 0.029 mol) and nitromethane 2 (1.06 g, 0.0174 mol) and the reaction mixture was stirred at rt for 2 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was evaporated under reduced pressure. The crude material was dissolved in DCM (20 ml) and treated with TEA (6.06 ml, 0.0435 mol) and mesyl chloride (3.37 ml, 0.0435 mol) at 0 °C and the reaction mixture was stirred at rt for 30 min. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was evaporated under reduced pressure. The crude was purified by column chromatography by eluting with 10% ethyl acetate in hexane to yield the title compound XIXa as yellow solid; Yield: (2.47 g, 94%). LC_MS Calculated for <semantics>C8H8N2O3<annotation encoding="application / x-tex">C_8H_8N_2O_3< / annotation>< / semantics>: 180.05; Observe: 181.00 [M++H]. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 8.38 <semantics>(d,J=3.2 Hz,1H),7.43(d,J=8.4 Hz,1H),7.26(s,1H),7.22(dd,J=8.4,2.8 Hz,1Hz)<annotation encoding="application / x-tex">(d, J = 3.2 \text{ Hz}, 1\text{H}), 7.43 (d, J = 8.4 \text{ Hz}, 1\text{H}), 7.26 (s, 1\text{H}), 7.22 (dd, J = 8.4, 2.8 \text{ Hz}, 1\text{Hz})< / annotation>< / semantics> 1H), 3.92 (s,3H). Step-2: 2-(5-Methoxypyridin-2-yl) ethan-1-amine (XIX) [000149] To a stirred solution of (E)-5-methoxy-2-(2-nitrovinyl) pyridine 3 (2.74) g, 0.0152 mol) in THF (90 ml), was added LAH (1M sol in THF, 45.6 ml, 0.0456 mol) at -10 °C dropwise. Then the temp was allowed to reach to rt and the reaction mixture was stirred at rt for 2 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled to 0 °C and quenched with saturated Na2SO4 solution (50 ml) and extracted with ethyl acetate (50 ml x 3). The organic layer was dried with Na2SO4, filtered, and evaporated under reduced pressure. The crude was purified by column chromatography by eluting with 10% methanolic NH3 in DCM to yield the title compound XIX as brown liquid; Yield: (0.8 g, 34.78%). 1H NMR (400 MHz, DMSO): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 8.19 (d, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics> = 2.8 Hz, 1H), 7.3 (dd, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics> = 8.4, 3.2 Hz, 1H), 7.19 (d, <semantics>J=8.8 Hz,1H,3.79 (s, 3H),2.88 (t, J=6.0 Hz,2H),2.74 (t, J=6.8 Hz,2H).<annotation encoding="application / x-tex">J = 8.8 \text{ Hz}, 1\text{H}, 3.79 \text{ (s, 3H)}, 2.88 \text{ (t, } J = 6.0 \text{ Hz}, 2\text{H)}, 2.74 \text{ (t, } J = 6.8 \text{ Hz}, 2\text{H)}.< / annotation>< / semantics> [000150] Synthesis of a mixture of 7-amino-3-chloro-2-methyl-5-(methyl sulfonyl)pyrazolo[1,5-a] pyrimidine -6-carbonitrile (XX) and 7-amino-3-chloro- 2-methyl-5-(methyl sulfinyl) pyrazolo[1,5-a]pyrimidine-6-carbonitrile. (XXa). [Image disponible dans le document PDF, Image available in the PDF document] Step-1: Synthesis of 4-chloro-3-methyl-1H-pyrazol-5-amine (XXb). [000151] N-Chlorosuccinimide (3.3 g, 0.025 mol) was added portion wise to the stirred solution of 3-methyl-1H-pyrazol-5-amine (CAS: 268724-49-8, 2.0 g, 0.021 mol) in DCM (50 mL) at 0°C, Then the reaction mixture was stirred at rt for 1h. The progress of the reaction was monitored by TLC. Then the reaction mixture was diluted with water (20 mL) and extracted with ethyl acetate (3 x 50 mL). The combined organic layer was dried over anhydrous Na2SO4 and evaporated under reduced pressure to get the crude product. Crude compound obtained was purified by Biotage column chromatography using silica gel (230-400) and 1-5% methanol in DCM as eluent to afford desired product XXb as an off white solid. Yield: 2.0g, 74%. LCMS Calculated. for C4H6ClN3 is 131.56; Observed.132.0 [M+H] + Step-2: Synthesis of 7-amino-3-chloro-2-methyl-5-(methylthio) pyrazolo[1,5-a] pyrimidine-6- carbonitrile (XXc) [000152] To a stirred solution of 4-chloro-5-methyl-1H-pyrazol-3-amine XXb (1.8 g, 0.0136 mol) in pyridine (5 mL) was added 2-(bis (methylthio) methylene) malononitrile Ia (2.8 g, 0.016 mol). The resulting reaction mixture was heated at 120°C for 2.5 h. Then the progress of the reaction was monitored by TLC. Reaction mixture was cooled to room temperature and poured into ice cold water (20 mL). Precipitated compound was filtered and washed with cold water. Then the obtained solid was dried under vacuum and purified by biotage column chromatography using silica gel (230-400) and 5-20 % ethyl acetate in hexane as eluent to afford desired product XXc as pale brown colour solid. Yield: 3.5g, 99%. LCMS Calculated. for C9H8ClN5S is 253.71; Observed.254.0 [M+H] +. 1H NMR (400 MHz, DMSO-D6): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 8.90 (bs, 2H), 2.57 (S, 3H), 2.37 (S, 3H). Step-3: Synthesis of 7-amino-3-chloro-2-methyl-5-(methyl sulfonyl) pyrazolo[1,5-a] pyrimidine-6-carbonitrile. (XX) and 7-amino-3-chloro-2- methyl-5- (methyl sulfinyl) pyrazolo [1,5-a] pyrimidine-6-carbonitrile (XXa) [000153] meta-Chloroperoxybenzoic acid (9.5 g, 0.055 mol) was added portion wise to a stirred solution of 7-amino-3-chloro-2-methyl-5-(methylthio) pyrazolo[1,5-a] pyrimidine -6-carbonitrile XXc (3.5 g, 0.013 mol) in DCM (50 mL) at 0°C. The reaction mixture was stirred at rt for 3 h. Then the progress of the reaction was monitored by TLC. The reaction mixture was quenched with aqueous NaHCO3 solution (50 mL) and extracted with DCM (3 x 50 mL). The combined organic layer was dried over anhydrous Na2SO4 and evaporated under reduced pressure and dried under vacuum to get a mixture of 7-amino-3-chloro-2-methyl-5- (methyl sulfonyl) pyrazolo[1,5-a] pyrimidine-6-carbonitrile XX and 7-amino-3- chloro-2-methyl-5- (methyl sulfinyl) pyrazolo [1,5-a] pyrimidine-6-carbonitrile XXa as an off white solid. Yield (2.2 g, 56%). This crude material was taken as such for next step without further purification. LCMS Calculated. for C9H8ClN5O2S is 285.71; Observed .286.1 [M+H] 1H NMR (400 MHz, DMSO- D6): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 9.48 (bs, 2H), 3.42 (S, 3H), 2.45 (S, 3H). Synthesis of 2-(6-(methoxymethyl) pyridin-2-yl) ethan-1-amine (XXI) [Image disponible dans le document PDF, Image available in the PDF document] Step-1: Synthesis of methyl 6-methoxy methyl) picolinate. (XXIa) [000154] A solution of methyl 6-(hydroxymethyl) picolinate (CAS: 1197-10- 0, 25 g, 0.15 mol) in DMF (250 mL) was cooled to 0°C, added NaH (7.2 g, 60%) wt, 0.18 mol) portion wise and dimethyl sulphate (19 mL, 0.19 mol) dropwise to it and the reaction mixture was stirred at rt for 3 hours. Then the progress of the reaction was monitored by TLC. After completion, the reaction mixture was quenched with ice cold water (200 mL) and extracted with ethyl acetate (3 x 200 mL) and concentrated. Crude product obtained was purified by gravity column used 230-400 silica mesh and the desired product was eluted at 15-20% ethyl acetate in hexane to afford XXIa as yellow viscous oil. Yield: 21 g, 78%. LCMS Calculated. for C9H11NO3 is 181.07; Observed 182.20 [M+H]. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 8.04 (d, <semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics> Hz, 1H), 7.86 (t, <semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics> Hz 1H,), 7.66 (d, <semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics>Hz, 1H,), 4.69(s, 2H), 4.00 (s, 3H), 3.49(s, 3H). Step-2: Synthesis of (6-(methoxy methyl) pyridin-2-yl) methanol (XXIb) [000155] A solution of methyl 6-(methoxymethyl) picolinate XXIa (21 g, 0.12 mol) in THF (200 mL) was cooled to 0°C, added NaBH4 (13 g, 0.35) mol) portion wise and then reaction mixture was stirred at 25°C for 3 hours. The progress of the reaction was monitored by TLC. Reaction mixture concentrated at low vacuum and added NaHCO3 solution (100 mL) and extracted with DCM (3 x 300 mL). The combined organic layer was dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure. Crude compound obtained was purified by gravity column used 230-400 silica mesh and the desired product was eluted at 25- 30% ethyl acetate in hexane to afford XXIb as yellow viscous oil. Yield: 16.8 g, 93%. LCMS Calculated. for C8H11NO2 is 153.08; Observed 154.25 [M+H] +.1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.69 (t, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>=7.6 Hz, 1H), 7.33 (d, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>=7.6 Hz, 1H), 7.14(d, <semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics>Hz, 1H,), 4.74 (d, <semantics>J=4.8<annotation encoding="application / x-tex">J = 4.8< / annotation>< / semantics> Hz, 2H), 4.59(s, 2H), 3.77(t, <semantics>J=4.8<annotation encoding="application / x-tex">J = 4.8< / annotation>< / semantics>, 5.2 Hz, 1H) 3.48 (s, 3H). Step-3: Synthesis of (6-(methoxy methyl) pyridin-2-yl) methyl methane sulfonate (XXIc) [000156] A solution of (6-(methoxymethyl) pyridin-2-yl) methanol XXIb (7 g, 0.05 mol) in DCM (140 mL) was cooled to 0 °C, added TEA (7 g, 0.01 L, 0.07 mol) and MsCl (4 mL, 0.05 mol) dropwise and the reaction mixture was stirred at 0°C for 2 hours. The progress of the reaction was monitored by TLC. Reaction mixture was quenched with NaHCO3 solution (100 mL) and extracted with DCM (3x 200 mL) and the combined organic layer was dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure to get brown liquid XXIc which was used as such for the next step without further purification. Yield: 10 g, 92%. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.79-7.75 (m,1H), 7.42 (d, 1H, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics> = 8.0 Hz), 7.38 <semantics>(d,J=7.6Hz,1H),5.32(s,2H),4.57(s,2H),3.48(s,3H),3.09(s,3H).<annotation encoding="application / x-tex">(d, J = 7.6Hz, 1H), 5.32 (s, 2H), 4.57 (s, 2H), 3.48(s, 3H), 3.09(s, 3H).< / annotation>< / semantics> Step-4: Synthesis of 2-(6-(methoxy methyl) pyridin-2-yl) acetonitrile (XXId) [000157] To a stirred solution of (6-(methoxymethyl) pyridin-2-yl) methyl methane sulfonate XXIc (10 g, 0.043 mol) in DMF (100 mL) was added NaCN (2.3 g, 0.048 mol) portion wise and the reaction mixture was stirred at 24°C for 3 hours. The progress of the reaction was monitored by TLC. Reaction Mixture quenched with ice cold water (100 mL) and extracted with EtOAc (3 x 100 mL). The combined organic layer was dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure. The crude material obtained was purified by flash Chromatography using silica gel 230-400 mesh, the desired product was eluted with 20 - 25% EtOAc in hexane to afford XXId as yellow viscous oil. Yield: 5.1g, 73%. LCMS Calculated. for C9H10N2O is 162.08; Observed 163.25 [M+H] <semantics>+<annotation encoding="application / x-tex">^{+}< / annotation>< / semantics>. H NMR (400 MHz, CDCl3) <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.7-7.7 (m, 1H), 7.40-7.26 (m, 2H), 4.56(s, 2H), 3.92 (s, 2H), 3.48(s, 3H). Step-5: Synthesis of 2-(6-(methoxy methyl) pyridin-2-yl) ethan-1-amine (XXI) [000158] A solution of 2-(6-(methoxymethyl) pyridin-2-yl) acetonitrile XXId (5.1 g, 0.031 mol) in THF (80 mL) was cooled to 0°C and added BH3.DMS (15 mL, 0.16 mol) dropwise and the reaction mixture was stirred at 70°C for 3 hours. The progress of the reaction was monitored by TLC. After completion, the reaction was cooled to room temperature and quenched by MeOH (15 mL). The resulting mixture was stirred at room temperature for 30 min. The mixture was acidified using 1 M HCl solution (15 mL) and concentrated under reduced pressure. The residue obtained was taken in water (20 mL) and EtOAc (50 mL) and DCM (50 mL) were added to remove the impurities. The aqueous layer was separated and basified with 2N NaOH solution. The resulting mixture was extracted with DCM (3 x 300 mL). The combined organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to afford the desired compound XXI as a brown viscous liquid. The crude compound was used in the next step without further purification. Yield: 3.4 g, 65%. LCMS Calculated. for C9H11NO3 is 166.11; Observed 167.30 [M+H] <semantics>+<annotation encoding="application / x-tex">^+< / annotation>< / semantics>. 1H NMR (400 MHz, CDCL3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.64-7.60 (m, 1H), <semantics>7.26<annotation encoding="application / x-tex">7.26< / annotation>< / semantics> (d, <semantics>J=8<annotation encoding="application / x-tex">J = 8< / annotation>< / semantics> Hz, 1H), <semantics>7.07<annotation encoding="application / x-tex">7.07< / annotation>< / semantics>(d, <semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics>Hz, 1H), <semantics>4.56<annotation encoding="application / x-tex">4.56< / annotation>< / semantics>(s, 2H), <semantics>3.47<annotation encoding="application / x-tex">3.47< / annotation>< / semantics> (s, 3H), 3.10-3.07(m, 2H), 2.93-2.90(m, 2H). Synthesis of (1-(6-(2-aminoethyl) pyridin-2-yl) cyclopropyl) methanol (XXII) [Image disponible dans le document PDF, Image available in the PDF document] Step-1: Synthesis of Ethyl 2-(6-bromopyridin-2-yl) acetate (XXIIa) [000159] To a solution of lithium diisopropylamide (8 g, 0.04 L, 2M, 2.5 eq, 0.07 mol) in THF (150 mL) at -78 °C under nitrogen atmosphere was added 2- bromo-6-methylpyridine (CAS: 5315-25-3, 5 g, 1 eq, 0.03 mol) dropwise and the resulting mixture was stirred at -78 °C for 30 min. This was followed by an addition of diethyl carbonate (9 g, 2.5 eq, 0.07 mol). The resulting mixture was stirred at - 40 °C for 6 hours. The progress of the reaction was monitored by TLC for the absence of starting material. The reaction was quenched with saturated solution of NH4Cl (60 mL) and the resulting mixture was extracted with ethyl acetate (70 mL) X 2). The combined organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford light brown viscous liquid. The crude compound was purified by column chromatography using silica gel (100-200; 250g) and EtOAc (0-10%) in hexane as eluent. The peak eluted with 7% of EtOAc in hexane was concentrated to afford the desired product XXIIa as a colorless viscous liquid. Yield: 5.3 g, 70%. LCMS Calculated. for C9H10BrNO2 is 242.99; Observed. 244.10 [M+H]+. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.53 (t, <semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics> Hz, 1H), 7.40 (d, <semantics>J=8.0<annotation encoding="application / x-tex">J = 8.0< / annotation>< / semantics> Hz, 1H), 7.28 (t, <semantics>J=7.2<annotation encoding="application / x-tex">J = 7.2< / annotation>< / semantics> Hz, 1H), 4.19 (q, <semantics>J=7.2<annotation encoding="application / x-tex">J = 7.2< / annotation>< / semantics> Hz, 2H), 3.83 (s, 2H), 1.27 (t, <semantics>J=6.8<annotation encoding="application / x-tex">J = 6.8< / annotation>< / semantics> Hz, 3H). Step-2: Synthesis of Ethyl 1-(6-bromopyridin-2-yl) cyclopropane-1- carboxylate (XXIIb) [000160] A stirred solution of ethyl 2-(6-bromopyridin-2-yl) acetate XXIIa (4.2 g, 1 eq, 17 mmol) in DMF (25 mL) was cooled to 0° C sodium hydride (1.5 g, 60% Wt. 2.2 eq, 38 mmol) was added. To the resulting mixture 1,2-dibromoethane (7.1 g, 2.2 eq, 38 mmol) was added drop wise and stirred at rt for 4 hr. The reaction was monitored by TLC for the absence of starting material. To the reaction mixture (25 mL) ice cold water was added and the resulting mixture was extracted with ethyl acetate (25 mL x 2). The combined organic layer was given brine wash, dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to afford a pale brown viscous liquid. The crude compound was purified by silica gel (100-200; 24g) column chromatography using EtOAc (0-20%) in hexane. The peak eluted with 7% EtOAc in hexane was concentrated to afford the desired product XXIIb as a pale brown viscous liquid. Yield: 4.1 g, 88%. LCMS Calculated. for C11H12BrNO2 is 271.00; Observed. 272.05 [M+H]+. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.54 (d, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics> = 7.6 Hz, 1H), 7.50 (t, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics> = 7.6 Hz, 1H), 7.34 (d, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics> = 7.6 Hz, 1H), <semantics>4.15<annotation encoding="application / x-tex">4.15< / annotation>< / semantics> (q, <semantics>J=7.2<annotation encoding="application / x-tex">J = 7.2< / annotation>< / semantics> Hz, 2H), <semantics>1.67<annotation encoding="application / x-tex">1.67< / annotation>< / semantics> (t, <semantics>J=4.4<annotation encoding="application / x-tex">J = 4.4< / annotation>< / semantics> Hz, 2H), <semantics>1.50<annotation encoding="application / x-tex">1.50< / annotation>< / semantics> (t, <semantics>J=4.4<annotation encoding="application / x-tex">J = 4.4< / annotation>< / semantics> Hz, 2H), 1.23 (t, <semantics>J=7.2<annotation encoding="application / x-tex">J = 7.2< / annotation>< / semantics> Hz, 3H). Step-3: Synthesis of Ethyl 1-(6-vinylpyridin-2-yl) cyclopropane-1-carboxylate (XXIIc) [000161] A solution of ethyl 1-(6-bromopyridin-2-yl) cyclopropane-1- carboxylate XXIIb (2.8 g, 1 eq, 10 mmol), potassium trifluoro(vinyl)borate (1.7 g, 1.2 eq, 12 mmol) and potassium phosphate, tribasic (3.3 g, 1.3 mL, 1.5 eq, 16 mmol) in 1,4-dioxane (20 mL) was purged with N2 gas for 15 min with vigorous stirring. To the reaction was added PdCl2(dppf) (0.38 g, 0.05 eq, 0.52 mmol) and heated to 120 °C for 16 hours. The progress of the reaction was monitored by TLC analysis. The reaction was cooled to room temperature and reaction mixture was concentrated under reduced pressure. The residue was added water (70 mL) and the resulting mixture was extracted with ethyl acetate (50 mL x 2). The organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford a light brown viscous liquid. The crude compound was purified by combi- flash (230-400, 120 g packed) column chromatography using ethyl acetate in hexane and peak eluted with 5% EtOAc in hexane was concentrated to afford XXIIc as a light brown viscous liquid; Yield: 1 g, 40%. LCMS Calculated. for C13H15NO2 is 217.11; Observed. 218.25 [M+H]+ 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.58 (t, <semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics> Hz, 1H), 7.41 (d, <semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics> Hz, 1H), 7.19 (d, <semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics> Hz, 1H), 6.78 (q, <semantics>J=6.4 Hz<annotation encoding="application / x-tex">J = 6.4 \text{ Hz}< / annotation>< / semantics>, 1H), 6.17 (dd, <semantics>J=17.4&1.6 Hz<annotation encoding="application / x-tex">J = 17.4 \& 1.6 \text{ Hz}< / annotation>< / semantics>, 1H), 5.43 (dd, <semantics>J=11.0&1.2 Hz<annotation encoding="application / x-tex">J = 11.0 \& 1.2 \text{ Hz}< / annotation>< / semantics>, 1H), <semantics>4.15(q,J=7.2Hz,2H),1.65−1.63(m,2H),1.56−1.53(m,2H),1.21(t,J=7.2Hz,2H)<annotation encoding="application / x-tex">4.15 (q, J = 7.2 Hz, 2H), 1.65-1.63 (m, 2H), 1.56-1.53 (m, 2H), 1.21 (t, J = 7.2 Hz, 2H)< / annotation>< / semantics> 3H).; Step-4: Synthesis of Ethyl 1-(6-formylpyridin-2-yl) cyclopropane-1- carboxylate (XXIId) [000162] To a solution of ethyl 1-(3-vinylphenyl) cyclopropane-1-carboxylate XXIIc (1 g, 1 eq, 5 mmol) in THF (18 mL) and water (40 mL) osmium tetra-oxide (4.68 mL, 2.5% Wt. in isobutanol, 0.1 eq, 0.5 mmol) was added and the reaction was stirred at rt for 30 min. Then sodium metaperiodate (1 g, 0.4 mL, 1.5 eq, 7 mmol) was added and the reaction was stirred at rt for 2 h. The progress of the reaction was monitored by TLC analysis. The mixture was diluted with water (50 mL) and extracted with EtOAc (50 mL x 2). The combined organic layer was dried over anhydrous Na2SO4, filtered and evaporated under vacuum to afford XXIId as brown viscous liquid. The crude was used in the next step without further purification. Yield: 0.95 g, 90 %). %. LCMS Calculated. for C13H14O3 is 219.09; Observed. 220.20 [M+H] <semantics>+<annotation encoding="application / x-tex">^+< / annotation>< / semantics>. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 10.02 (s, 1H), 7.3 (s, 3H), <semantics>4.18<annotation encoding="application / x-tex">4.18< / annotation>< / semantics> (q, <semantics>J=7.2<annotation encoding="application / x-tex">J = 7.2< / annotation>< / semantics> Hz, 2H), <semantics>1.73−1.61<annotation encoding="application / x-tex">1.73-1.61< / annotation>< / semantics> (m, 4H), <semantics>1.22<annotation encoding="application / x-tex">1.22< / annotation>< / semantics> (t, <semantics>J=7.2<annotation encoding="application / x-tex">J = 7.2< / annotation>< / semantics> Hz, 3H). Step-5: Synthesis of Ethyl (<semantics>E<annotation encoding="application / x-tex">E< / annotation>< / semantics>)-1-(6-(2-nitrovinyl) pyridin-2-yl) cyclopropane- 1-carboxylate (XXIIe) [000163] A stirred solution of ethyl 1-(6-formylpyridin-2-yl) cyclopropane-1- carboxylate XXIId (950 mg, 1 eq. 4.33 mmol) in DCM (20 mL) was cooled to 0 °C. To the resulting mixture nitromethane (317 mg, 280 µL, 1.2 eq, 5.20 mmol), triethylamine (2.19 g, 3.02 mL, 5 eq, 21.7 mmol) were added under N2 gas. The resulting mixture was stirred at rt for 2 h. The reaction mixture was concentrated under reduced pressure to afford a brown viscous liquid. The mixture was dissolved in fresh DCM (20 mL) and was cooled to 0 °C. Then triethylamine (2.19 g, 3.02 mL, 5 eq, 21.7 mmol) was added to the reaction and this was followed by a drop- wise addition of mesylchloride (1.49 g, 1.01 mL, 3 eq, 13.0 mmol) under N2 gas. The reaction mixture was stirred at rt for 30 min. The progress of the reaction was monitored by TLC analysis which indicated completion of the reaction. The reaction mixture was concentrated under reduced pressure and water (15mL) was added and extracted with ethyl acetate (15 mL x 2). The combined organic layer was given brine wash, dried over anhydrous sodium sulphate, and concentrated under reduced pressure to afford XXIIe as brown viscous liquid. The crude product was taken for next step without further purification. Yield: 1.0 g, 86 %. LCMS Calculated. for C13H14N2O4 is 262.10; Observed.263.20 [M++H] Step-6: Synthesis of (1-(6-(2-Aminoethyl) pyridin-2-yl) cyclopropyl) methanol (XXII) [000164] To an ice-cold solution of LiAlH4 (20 mL, 1M, 4 eq.) in dry diethyl ether (80 mL) solution was dropwise added a solution of ethyl (E)-1-(6-(2- nitrovinyl) pyridin-2-yl) cyclopropane-1-carboxylate XXIIe (1 g, 1 eq, 4 mmol) in dry diethyl ether (7 mL). The resulting mixture was stirred at rt for 1 hr. The reaction was monitored by TLC analysis which indicated the completion of reaction. The reaction mixture was cooled to 0 °C and quenched water (2mL) followed by with 15% KOH solution (3mL). To the mixture was added ethyl acetate (100 mL) and stirred at rt for 20 min. The reaction mixture was filtered, and the residue was washed with 100 mL of ethyl acetate. The combined filtrate was concentrated under reduced pressure to afford a desired compound as pale brown viscous liquid XXII. The crude was used in the next step without further purification. Yield: 0.6 g, 80 %. LCMS Calculated. for C11H16N2O is 192.13; Observed. 193.25 [M+H] +. 1H NMR (400 MHz, DMSO-D6): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.52-7.50 (m, 1H), 6.98 (d, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics> = 8.0 Hz, 1H), 6.70 (d, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics> = 8.0 Hz, 1H), 3.83 (d, <semantics>J=3.6<annotation encoding="application / x-tex">J = 3.6< / annotation>< / semantics> Hz, 4H), 3.13 (t, <semantics>J=6.8<annotation encoding="application / x-tex">J = 6.8< / annotation>< / semantics> Hz, 2H), 2.90 (t, <semantics>J=6.4<annotation encoding="application / x-tex">J = 6.4< / annotation>< / semantics> Hz, 2H); 1.05-1.01 (m, 2H) 0.90-0.85 (m, 2H). Synthesis of 2-(1-(2-methoxyethyl)-1H-pyrazol-3-yl) ethan-1-amine (XXIII) [Image disponible dans le document PDF, Image available in the PDF document] Step-1: Synthesis of 1-(2-methoxyethyl)-1H-pyrazole-3-carbaldehyde) XXIIIa. [000165] 1-bromo-2-methoxyethane (5.2 g, 0.037mol) was added dropwise to a stirred solution of 1H-pyrazole-3-carbaldehyde (CAS: 3920-50-1: 3.0 g, 0.031mol) and CS2CO3 (20.0 g, 0.0624 mol) in DMF (50 mL) at 0°C. Then reaction mixture was stirred at rt for 3h. The progress of the reaction was monitored by TLC. Then the reaction mixture was diluted with water (500 mL) and extracted with ethyl acetate (3 x 50 mL). The combined organic layer was washed with water (50 mL). the combined organic layer was dried over anhydrous Na2SO4 and evaporated under reduced pressure to get crude product. Crude product obtained was purified by biotage column chromatography using silica gel (230-400 mesh) and the desired product was eluted at 5-20 % ethyl acetate in hexane to afford XXIIIa as colourless liquid Yield: 3.2 g, 66%. LCMS Calculated. for C7H10N2O is 154.17; Observed.155.2 [M+H] <semantics>+<annotation encoding="application / x-tex">^{+}< / annotation>< / semantics>. H NMR (400 MHz, DMSO-D6): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 9.97 (S, 1H), 7.54 <semantics>(d,J=1.6 Hz,1H),6.80(d,J=2.0 Hz,1H),4.38(t,J=4.8 Hz,2H),3.78(t,J=5.6 Hz)<annotation encoding="application / x-tex">(d, J = 1.6 \text{ Hz}, 1\text{H}), 6.80 (d, J = 2.0 \text{ Hz}, 1\text{H}), 4.38 (t, J = 4.8 \text{ Hz}, 2\text{H}), 3.78 (t, J = 5.6 \text{ Hz})< / annotation>< / semantics> Hz, 2H), 3.34(S, 3H). Step-2: Synthesis of (E)-1-(2-methoxyethyl)-3-(2-nitrovinyl)-1H-pyrazole XXIIIb. [000166] A mixture of 1-(2-methoxyethyl)-1H-pyrazole-3-carbaldehyde XXIIIa (3.2 g, 0.019 mol), nitromethane (35 g, 31mL, 0.57 mol) and ammonium acetate (2.2 g, 0.029 mol) were taken in a round bottom flask and the reaction mixture was stirred at 100°C for 2 h. Then the progress of the reaction was monitored by TLC for the absence of staring material. The reaction mixture was evaporated under vacuum to get crude residue which was purified by biotage column chromatography using silica (230-400 mesh). The desired product was eluted at 5-20% ethyl acetate in hexane as eluent to afford desired product as colourless liquid XXIIIb. Yield: 2.4 g, 60%. LCMS Calculated. for C8H11N3O3 is 197.19; Observed.198.2 [M+H] +. Step-3: Synthesis of 2-(1-(2-methoxyethyl)-1H-pyrazol-3-yl) ethan-1-amine XXIII. [000167] To a stirred solution of LAH 1.0M in THF (50mL, 0.048 mol) in diethyl ether (125 mL), was added (E)-1-(2-methoxyethyl)-3-(2-nitrovinyl)-1H- pyrazole XXIIIb (2.4g, 0.012mol) in THF (5 ml) at 0°C, under argon atmosphere. The reaction mixture was stirred at rt for 2 h. Then the progress of the reaction was monitored by TLC. The reaction mixture was quenched with water (2.4 ml) at 0°C followed by addition of 15% KOH solution (2.4 mL) and water (8 mL). Then the reaction mixture was filtered and washed the solid with ethyl acetate (3 x 100 mL). The combined organic layer was dried over anhydrous Na2SO4 and evaporated under reduced pressure to get crude XXIII as pale-yellow liquid. Yield: 1.5 g, 83% crude. Synthesis of (1-(3-(2-aminoethyl)-1H-pyrazol-1-yl) cyclopropyl) methanol. (XXIV) [Image disponible dans le document PDF, Image available in the PDF document] Step-1: Synthesis of methyl 1-(3-formyl-1H-pyrazol-1-yl) cyclopropane-1- carboxylate (XXIVa) [000168] Methyl 2,4-dibromobutanoate (CAS: 29547-04-4, 35 g, 0.14 mol) was added to the stirred solution of 1H-pyrazole-3-carbaldehyde (CAS: 3920-50-1, 10 g, 0.1 mol), K2CO3 (58 g, 0.42 mol) in DMF (100 mL) at 0°C. Then the reaction mixture was stirred at room temperature for 16 hours. Progress of the reaction was monitored by TLC analysis. Reaction mixture was quenched with cold water and extracted with ethyl acetate (2x 200 mL). The combined organic layer was washed with water (3x 100 mL) and followed by brine solution, dried over anhydrous sodium sulphate, and concentrated. The crude material was purified by combi-flash using 80g column, eluted with 0-25% ethyl acetate: hexane, to afford XXIVa as white solid. Yield: 13.5 g, 67%. LCMS Calculated. for C9H10N2O3 is 194.07; Observed. 195.15 [M+H] <semantics>+<annotation encoding="application / x-tex">^+< / annotation>< / semantics>. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 9.97 (s, 1H), 7.58 <semantics>(s,1H)<annotation encoding="application / x-tex">(s,1H)< / annotation>< / semantics>, 6.82 <semantics>(s,1H)<annotation encoding="application / x-tex">(s,1H)< / annotation>< / semantics>, 3.70 <semantics>(d,J=6.8Hz,3H)<annotation encoding="application / x-tex">(d, J = 6.8 Hz, 3H)< / annotation>< / semantics>, 1.93-1.90 <semantics>(m,2H)<annotation encoding="application / x-tex">(m, 2H)< / annotation>< / semantics>, 1.73-1.70 <semantics>(m,2H)<annotation encoding="application / x-tex">(m, 2H)< / annotation>< / semantics>. Step-2: Synthesis of methyl (E)-1(3-(2-nitrovinyl)-1H-pyrazol-1-yl) cyclopropane-1-carboxylate (XXIVb) [000169] To a stirred solution of ethyl 1-(3-formyl-1H-pyrazol-1-yl) cyclopropane-1-carboxylate XXIVa (1 g, 0.0051 mol) in toluene (25 mL) was added ammonium acetate (0.6 g, 0.0077 mol) and nitromethane (3.1g, 0.051 mol), and the resulting mixture was stirred at 100 °C for 16 hrs. The progress of the reaction was monitored by TLC. After completion of the reaction, reaction mixture was quenched with 1N HCl solution (20 mL), extracted with ethyl acetate (2x 20 mL). The combined organic layer was washed with brine solution (15 mL), dried over anhydrous sodium sulphate. Solvent was removed under vacuum. The crude compound was passed through flash column and eluted with 10-20% ethyl acetate in hexane to afford XXIVb as white solid. Yield: 1.2 g, 35%. LCMS Calculated. for C10H11N3O4 is 237.07; Observed. 238.15 [M+H] +. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.95 (d, <semantics>J=13.6<annotation encoding="application / x-tex">J = 13.6< / annotation>< / semantics> Hz, 1H), 7.61 (d, <semantics>J=13.6<annotation encoding="application / x-tex">J = 13.6< / annotation>< / semantics> Hz, 1H), 7.57 (d, <semantics>J=2.4<annotation encoding="application / x-tex">J = 2.4< / annotation>< / semantics> Hz, 1H), <semantics>6.56<annotation encoding="application / x-tex">6.56< / annotation>< / semantics> (d, <semantics>J=2.4<annotation encoding="application / x-tex">J = 2.4< / annotation>< / semantics> Hz, 1H), <semantics>3.7<annotation encoding="application / x-tex">3.7< / annotation>< / semantics> (s, 3H), <semantics>1.91−1.87<annotation encoding="application / x-tex">1.91-1.87< / annotation>< / semantics> (m, 2H), <semantics>1.7−1.66<annotation encoding="application / x-tex">1.7-1.66< / annotation>< / semantics> (m, 2H). Step-3: Synthesis of (1-(3-(2-aminoethyl)-1H-pyrazol-1-yl) cyclopropyl) methanol (XXIV). [000170] Methyl (E)-1(3-(2-nitrovinyl)-1H-pyrazol-1-yl) cyclopropane-1- carboxylate XXIVb (0.430 g, 0.0018 mol) in THF (5 mL) was added dropwise to a stirred solution of LAH (1M in THF, 7.25 ml, 0.0072 mol) in Et2O (10 mL) at 0°C and stirred the reaction mixture for 1 hr at room temperature. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was cooled to 0°C and quenched with water (0.4 mL) followed by 15% KOH solution (0.4 mL), water (1.2 mL) and the reaction mixture was stirred for 15- 20 min. Reaction mixture was filtered and washed with EtOAc (3 x 20). The combined organic layer was dried over anhydrous sodium sulphate. Concentrated the solvent under reduced pressure to get pale yellow oil XXIV. Yield: 0.329 g, 93.8%. LCMS Calculated. for C9H15N3O is 181.24; Observed. 182.25 [M+H] +. 1H NMR (400 MHz, DMSO-d6): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.40 (d, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics> = 2.4 Hz, 1H), 6.05 (d, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics> = 2.0 Hz, 1H), <semantics>3.74<annotation encoding="application / x-tex">3.74< / annotation>< / semantics> (s, <semantics>3H<annotation encoding="application / x-tex">3H< / annotation>< / semantics>), <semantics>2.98<annotation encoding="application / x-tex">2.98< / annotation>< / semantics> (t, <semantics>J=6.8<annotation encoding="application / x-tex">J = 6.8< / annotation>< / semantics> Hz, <semantics>2H<annotation encoding="application / x-tex">2H< / annotation>< / semantics>), <semantics>2.76<annotation encoding="application / x-tex">2.76< / annotation>< / semantics> (t, <semantics>J=7.2<annotation encoding="application / x-tex">J = 7.2< / annotation>< / semantics> Hz, <semantics>2H<annotation encoding="application / x-tex">2H< / annotation>< / semantics>), <semantics>1.26−1.23<annotation encoding="application / x-tex">1.26-1.23< / annotation>< / semantics> (m, <semantics>2H<annotation encoding="application / x-tex">2H< / annotation>< / semantics>), 1.09-1.08 (m, 2H). Synthesis of (2-(6-(2-aminoethyl) pyridin-2-yl) cyclopropyl) methanol (XXV). [Image disponible dans le document PDF, Image available in the PDF document] Step-1: Synthesis of ethyl (E)-3-(6-bromopyridin-2-yl) acrylate (XXVa) [000171] To a suspension of sodium hydride (3.2 g, 55% wt, 1.35 eq, 73 mmol) in THF (300 mL) was dropwise added ethyl 2-(diethoxy phosphoryl) acetate (CAS:867-13-0, 15 g, 1.25 eq, 67 mmol) at 0 °C. After 30 min, solution of 6- bromopicolinaldehyde (10 g, 1 eq, 54 mmol) in 30 mL THF was added and the reaction mixture was stirred at rt for 4h. the progress of reaction was monitored by TLC analysis. After completion of the reaction, the reaction was cooled to 0 °C and water (75 mL) was dropwise added. The resulting mixture was extracted with ethyl acetate (75 mL X 2). The combined organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford the light brown viscous liquid. The crude compound was purified by silica gel (100-200; 150g) column chromatography using EtOAc (0-20%) in hexane. The peak eluted with 10% of EtOAc in hexane was concentrated to afford XXVa as an off white solid. Yield: 10 g, 73%. LCMS Calculated. for C10H10BrNO2 is 254.99; Observed. 256.05 [M+H] +. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.60-7.54 (m, 2H), 7.45 (d, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics> = 8.0 Hz, 1H), 7.35 <semantics>(d,J=7.6 Hz,1H),6.96(d,J=15.2 Hz,1H),4.27(q,J=7.2 Hz,2H),1.33(t,J=7.6 Hz,1Hz)<annotation encoding="application / x-tex">(d, J = 7.6 \text{ Hz}, 1\text{H}), 6.96 (d, J = 15.2 \text{ Hz}, 1\text{H}), 4.27 (q, J = 7.2 \text{ Hz}, 2\text{H}), 1.33 (t, J = 7.6 \text{ Hz}, 1\text{Hz})< / annotation>< / semantics> 7.2 Hz, 3H. Step-2: Synthesis of ethyl 2-(6-bromopyridin-2-yl) cyclopropane-1- carboxylate (XXVb) [000172] To a solution of Trimethylsulfoxonium lodide (CAS: 1774-47-6, 19 g, 2.2 eq, 86 mmol) in DMSO (140 mL) was added sodium hydride portion wise (2.2 g, 55% Wt. 1.3 eq, 51 mmol) and the resulting mixture was stirred for one hour at room temperature. A solution of ethyl <semantics>(E)<annotation encoding="application / x-tex">(E)< / annotation>< / semantics>-3-<semantics>(6<annotation encoding="application / x-tex">(6< / annotation>< / semantics>-bromopyridin-2-yl) acrylate <semantics>(10 g,<annotation encoding="application / x-tex">(10 \text{ g},< / annotation>< / semantics> 1 eq, 39 mmol) in mixture of DMSO (60 mL) and THF (60 mL) was slowly added to the reaction. The resulting mixture was stirred for four hours at room temperature. The progress of the reaction was monitored by TLC analysis. After completion of the reaction, 1N HCl (10 mL) was added, and the reaction mixture extracted with diethyl ether (30 mL X 2). The combined organic layer was dried over anhydrous sodium sulphate, the solvent was removed under vacuo. The crude compound was passed through a plug of silica gel (100-200; 120g) in ethyl acetate in hexane (7%) to afford the desired compound XXVb as a colourless viscous liquid. Yield: 6.0 g, 60%. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.57-7.39 (m, 1H), 7.27- 7.26 (m, 1H), 7.18 (d, <semantics>J=7.6<annotation encoding="application / x-tex">J = 7.6< / annotation>< / semantics> Hz, 1H), 4.25-4.12 (m, 2H), 2.58-2.51 (m, 2H), 2.29- 2.25 (m, 2H), 1.34-1.23 (m, 3H) Step-3: Synthesis of Ethyl 2-(6-vinylpyridin-2-yl) cyclopropane-1-carboxylate (XXVc) [000173] A solution of ethyl 2-(6-bromopyridin-2-yl) cyclopropane-1- carboxylate (3.9 g, 1 eq, 14 mmol), Potassium Vinyl trifluoroborate (CAS: 13682- 77-4, 2.1 g, 1.1 eq, 16 mmol) and potassium phosphate, tribasic (4.6 g, 1.8 mL, 1.5 eq, 22 mmol) in 1,4 dioxane (60 mL) was purged with N2 gas for 15 min with vigorous stirring. To the reaction was added PdCl2 (dppf) (0.53 g, 0.05 eq, 0.72 mmol) and the seal tube was closed and heated to 120 °C for 16 hours. The progress of the reaction was monitored by TLC analysis. After completion of the reaction, it was cooled to room temperature and reaction mixture was concentrated under reduced pressure. To the residue obtained was added water (80 mL) and the resulting mixture was extracted with ethyl acetate (50 mL x 2). The organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford a light brown viscous liquid. The crude compound was purified by combi- flash (230-400, 120g packed) column chromatography using ethyl acetate in hexane and peak eluted with 5% EtOAc in hexane was concentrated to afford XXVc as a pale-yellow viscous liquid. Yield: 1.8 g, 57%. LCMS Calculated. for C13H15NO2 is 217.11; Observed. 218.20 [M+H]+. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.51 (t, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics> = 7.2 Hz, 1H), 7.10-7.07 (m, 2H), 6.78-6.68 (m,1H), 6.78-6.68 (m, 1H), 5.42-5.39 (m, 1H), 4.19-4.14 (m, 1H), 2.63-2.57 (m, 2H), 2.31-2.29 (m, 1H), 1.66-1.56 (m, 2H), 1.34-1.26 (m, 3H). Step-4: Synthesis of ethyl 2-(6-formylpyridin-2-yl) cyclopropane-1- carboxylate (XXVd) [000174] To a solution of ethyl 2-(6-vinylpyridin-2-yl) cyclopropane-1- carboxylate XXVc (1.6 g, 1 eq, 7.4 mmol) in THF (4.4 mL) and water (10 mL) a solution of osmium tetroxide (7.4 mL g, 2.5% wt% in isobutanol, 0.1 eq, 0.74 mmol) was added and the reaction was stirred at rt for 30 min. Then, sodium metaperiodate (2.4 g, 0.59 mL, 1.5 eq, 11 mmol) was added and the reaction was stirred at rt for 2 h. Then the progress of the reaction was monitored by TLC analysis which indicated completion of the reaction. The mixture was diluted with water (35) mL) and extracted with EtOAc (30 mL x 2). The combined organic layer was dried over anhydrous Na2SO4, filtered and evaporated under vacuum to afford XXVd as brown viscous liquid. The crude product obtained was used as such in the next step without further purification. Yield: (1.56 g, 97 %). LCMS Calculated. for <semantics>C12H13NO3<annotation encoding="application / x-tex">C_{12}H_{13}NO_3< / annotation>< / semantics> is 219.09; Observed. 220.20 [M+H] +. 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 9.95 (s, 1H), 7.76-7.72 (m, 2H), 7.47-7.45 (m, 1H), 4.27-4.16 (m, 2H), 2.70-2.65 (m, 2H), 2.39-2.37 (m, 2H), 1.30-1.27 (m, 3H). Step-5: Synthesis of ethyl (E)-2-(6-(2-nitrovinyl) pyridin-2-yl) cyclopropane-1- carboxylate (XXVe) [000175] A stirred solution of ethyl 2-(6-formylpyridin-2-yl) cyclopropane-1- carboxylate XXVd (1.72 g, 1 eq, 7.85 mmol) in DCM (15 mL) was cooled to 0 °C. To the resulting mixture nitromethane (575 mg, 1.2 eq, 9.41 mmol) and triethylamine (2.19 mL, 2.0 eq, 15.7 mmol) were added under N2 gas. The resulting mixture was stirred at rt for 2 h. The reaction mixture was concentrated under reduced pressure to afford a brown viscous liquid. The mixture was dissolved in fresh DCM (10 mL) and was cooled to 0 °C. Then triethylamine (3.02 mL, 5 eq, 21.7 mmol) was added to the reaction and this was followed by a drop-wise addition of mesyl chloride (1.49 g, 1.01 mL, 3 eq, 13.0 mmol) under N2 gas. The reaction mixture was stirred at rt for 30 min. The progress of the reaction was monitored by TLC analysis which indicated completion of reaction. The reaction mixture was concentrated under reduced pressure and water (15 mL) was added and extracted with ethyl acetate (15 mL x 2). The combined organic layer was given brine wash, dried over anhydrous sodium sulphate, and concentrated under reduced pressure to afford XXVe as a brown viscous liquid. The crude was used in the next step without further purification. Yield: 1.87 g, 100 %. Step-6: Synthesis of (2-(6-(2-Aminoethyl) pyridin-2-yl) cyclopropyl) methanol (XXV) [000176] To a cooled LiAlH4 (30 mL, 1M, 4 eq.) in dry diethyl ether (160 mL) using ice bath, was added dropwise a solution of ethyl <semantics>(E)<annotation encoding="application / x-tex">(E)< / annotation>< / semantics>-2-<semantics>(6<annotation encoding="application / x-tex">(6< / annotation>< / semantics>-<semantics>(2<annotation encoding="application / x-tex">(2< / annotation>< / semantics>-nitrovinyl) pyridin-2-yl) cyclopropane-1-carboxylate (2 g, 1 eq, 8 mmol) in dry diethyl ether (7 mL). The resulting mixture was stirred at rt for 2 h. The reaction was monitored by TLC analysis which indicated the completion of reaction. The reaction mixture was cooled to 0 °C and quenched water (3 mL) followed by with 15% KOH solution (15 mL). To the mixture was added ethyl acetate (75 mL) and stirred at rt for 20 min. The reaction mixture was filtered, and the residue was washed with 100 mL of ethyl acetate. The combined filtrate was concentrated under reduced pressure to afford XXV as pale brown viscous liquid. The crude was used as such in the next step without further purification. Yield: 1.03 g, 100%. LCMS Calculated. for C11H16N2O is 192.13; Observed. 193.25 [M+H]+. Synthesis of 2-(6-ethylpyridin-2-yl) ethan-1-amine (XXVI) [Image disponible dans le document PDF, Image available in the PDF document] Step-1: Ethyl 2-(6-bromopyridin-2-yl) acetate (XXVIa) [000177] To a stirred solution of lithium diisopropylamide (110 mL, 2 molar, 220 mmol) in dry THF (500 mL) at -78 °C under inert atmosphere was dropwise added 2-bromo-6-methylpyridine (CAS:5315-25-3,15 g, 87 mmol) and the resulting mixture was stirred at -78 °C for 30 min. This was followed by an addition of diethyl carbonate (CAS: 105-58-8, 26 g, 220 mmol) mixture was stirred at -40 °C for 4 hours. The progress of the reaction was monitored by TLC analysis. After completion, the reaction was quenched with saturated solution of NH4Cl (150 mL), and the resulting mixture was extracted with ethyl acetate (170 mL x 2). The combined organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford light brown viscous liquid. The crude compound was purified by silica gel (100-200) column chromatography using ethyl acetate (0-10%) in n-hexane. The peak eluted with 7% of ethyl acetate in n-hexane was concentrated to afford the desired product XXVIa as a colorless viscous liquid. Yield: 12.2g (57%); LCMS Calculated. for C9H11BrNO2 is 246.00, Observed, 246.15; <semantics>[M+H]+<annotation encoding="application / x-tex">[M+H]^+< / annotation>< / semantics>; 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.53 (t, <semantics>J=<annotation encoding="application / x-tex">J=< / annotation>< / semantics> 7.6 Hz, 1H), 7.40 (d, <semantics>J=8.0 Hz,1H),7.28 (t, J=7.6 Hz,1H),4.19 (q, J=7.2 Hz,2H),3.83 (s, 2H),1.27<annotation encoding="application / x-tex">J=8.0 \text{ Hz}, 1\text{H}), 7.28 \text{ (t, } J=7.6 \text{ Hz}, 1\text{H}), 4.19 \text{ (q, } J=7.2 \text{ Hz}, 2\text{H}), 3.83 \text{ (s, } 2\text{H}), 1.27< / annotation>< / semantics> <semantics>(t,J=7.2Hz,3H).<annotation encoding="application / x-tex">(t, J= 7.2 Hz, 3H).< / annotation>< / semantics> Step-2: Ethyl 2-(6-vinylpyridin-2-yl) acetate (XXVIb) [000178] A solution of ethyl 2-(6-bromopyridin-2-yl) acetate XXVIa (3 g, 10.0 mmol), potassium trifluoro(vinyl)borate (2 g, 11.0 mol) and potassium phosphate, tribasic (4 g, 20 mmol) in 1,4 dioxane (40 mL) was purged with N2 gas for 15 min with vigorous stirring. To the reaction was added PdCl2(dppf) (0.4 g, 0.6 mmol) and the seal tube was closed and heated to 120 °C for 16 hours. The progress of the reaction was monitored by TLC analysis. The reaction was cooled to room temperature and reaction mixture was concentrated under reduced pressure. The residue was added water (70 mL) and the resulting mixture was extracted with ethyl acetate (75 mL x 2). The organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford a light brown viscous liquid. The crude compound was purified by combi-flash (230-400) column chromatography using ethyl acetate in n-hexane and peak eluted with 3% ethyl acetate in hexane was concentrated to afford the desired compound XXVIb as a colorless viscous liquid. Yield: 2.0g (90%); LCMS Calculated. for C11H14NO2 is 192.10, Observed, 192.25; <semantics>[M+H]+<annotation encoding="application / x-tex">[M+H]^+< / annotation>< / semantics>; 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.62 (t, <semantics>J=<annotation encoding="application / x-tex">J=< / annotation>< / semantics> 7.6 Hz, 1H), 7.25 (d, <semantics>J=7.6 Hz,1H,7.17 (d, J=7.6 Hz,1H),6.80 (q, J=6.4 Hz,1H),6.19 (d, J=17.6 Hz,1H)<annotation encoding="application / x-tex">J=7.6 \text{ Hz}, 1\text{H}, 7.17 \text{ (d, } J=7.6 \text{ Hz}, 1\text{H}), 6.80 \text{ (q, } J=6.4 \text{ Hz}, 1\text{H}), 6.19 \text{ (d, } J=17.6 \text{ Hz}, 1\text{H})< / annotation>< / semantics> Hz, 1H), 5.47 (d, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>= 10.8 Hz, 1H), 4.19 (q, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>= 7.2 Hz, 2H), 1.27 (t, <semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>= 7.2 Hz, 3H). Step-3: 2-(6-Vinylpyridin-2-yl) ethan-1-ol. (XXVIc) [000179] To a stirred solution of ethyl 2-(6-vinylpyridin-2-yl) acetate XXVIb (2 g, 10.0 mmol) in methanol (30 mL) under nitrogen atmosphere was portion wise added at 0 °C sodium borohydride (2 g, 50 mmol). The resulting mixture was stirred at 0 °C for 30 min and at room temperature for 6 h. The progress of the reaction was monitored by TLC analysis which indicates completion of reaction. To the reaction mixture saturated NaHCO3 solution (50 mL) was added and extracted with ethyl acetate (75 mL x 2). The organic layer was given brine (35 mL) wash, dried over anhydrous sodium sulphate, and concentrated under reduced pressure to afford XXVIc as colorless viscous liquid. The crude was taken for next step without further purification. Yield: 1.2 g (80%); LCMS Calculated. for C9H12NO is 150.09, Observed, 150.00; <semantics>[M+H]+<annotation encoding="application / x-tex">[M+H]^+< / annotation>< / semantics>; 1H NMR (400 MHz, CDCl3): <semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics> 7.59 (t, <semantics>J=<annotation encoding="application / x-tex">J=< / annotation>< / semantics> 7.6 Hz, 1H), <semantics>7.19<annotation encoding="application / x-tex">7.19< / annotation>< / semantics> (d, <semantics>J=7.6<annotation encoding="application / x-tex">J=7.6< / annotation>< / semantics> Hz, 1H), <semantics>7.02<annotation encoding="application / x-tex">7.02< / annotation>< / semantics> (d, <semantics>J=8.0<annotation encoding="application / x-tex">J=8.0< / annotation>< / semantics> Hz, 1H), <semantics>6.81−6.74<annotation encoding="application / x-tex">6.81-6.74< / annotation>< / semantics> (m, 1H), <semantics>6.16<annotation encoding="application / x-tex">6.16< / annotation>< / semantics> (d, <semantics>J=17.6 Hz,1H,5.47 (d, J=10.8 Hz,1H),4.03 (t, J=5.6 Hz,2H),3.01 (t, J=5.6 Hz,2H)<annotation encoding="application / x-tex">J=17.6 \text{ Hz}, 1\text{H}, 5.47 \text{ (d, } J=10.8 \text{ Hz}, 1\text{H}), 4.03 \text{ (t, } J=5.6 \text{ Hz}, 2\text{H}), 3.01 \text{ (t, } J=5.6 \text{ Hz}, 2\text{H})< / annotation>< / semantics> Hz, 2H). Step-4: 2-(6-Vinylpyridin-2-yl) ethyl methane sulfonate (XXVId) [000180] To a stirred solution of 2-(6-vinylpyridin-2-yl) ethan-1-ol XXVIc (1.2 g, 8.0 mmol) in DCM (30 mL) triethylamine (4.5 mL, 32 mmol) was added under nitrogen atmosphere. The resulting mixture was cooled to 0 °C and mesyl-Cl (0.81 mL, 10.0 mmol) was drop wise added. The reaction mixture was stirred at 0 °C for 30 min. The progress of the reaction was monitored by TLC analysis which indicates completion of reaction. To the reaction mixture water (30 mL) was added and extracted with DCM (30 mL X 3). The organic layer was washed...

Claims

<pat:ClaimStatement>I / We claim:< / pat:ClaimStatement> <pat:Claims com:id="claims"> <pat:Claim com:id="CLM-00001"> <pat:ClaimNumber>1< / pat:ClaimNumber> <pat:ClaimText>1. A compound of Formula I [Image disponible dans le document PDF, Image available in the PDF document] Formula I or its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, stereoisomers, and racemates thereof, wherein A is selected from C5-10 aryl, C2-10 heteroaryl, C3-6 cycloalkyl, or C1-10 heterocyclyl; wherein C5-10 aryl, C2-10 heteroaryl, C3-6 cycloalkyl, or C1-10 heterocyclyl is optionally substituted with one or more substituents selected from R6, R7, R8, R9, R9a, or oxo; R2 is selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 haloalkyl; R3 is selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 haloalkyl; wherein C1- 6 alkyl is optionally substituted with C1-6 alkoxy; R4 and R5 are independently selected from hydrogen, halogen, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, -CO-N(R10 R11), C4-10 carbocyclyl, or C1-10 heterocyclyl, wherein C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl are optionally substituted with one or more groups selected from C3-6 cycloalkyl, C1-6 alkoxy, or C1-10 heterocyclyl; or R4 and R5 are joined together to form C4-10 carbocyclyl, or C1-10 heterocyclyl, wherein <semantics>C4−10<annotation encoding="application / x-tex">C_{4-10}< / annotation>< / semantics> carbocyclyl or <semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics> heterocyclyl is optionally substituted with 1 to 3 groups independently selected from halogen, C1-6 alkyl, C1-6 alkoxy, or C1-6 haloalkoxy; R10 and R11 are independently selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkyl, C3-6 halocycloalkyl, C4-10 carbocyclyl, or C1-10 heterocyclyl; R6 is selected from hydrogen, halogen, hydroxyl, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylhydroxy, C1-6 aminoalkyl, C3-6 cycloalkyl, C3-6 halocycloalkyl, -Y-O-C1-6 alkyl, -Y-O-C3-6 cycloalkyl, -Y-CO-NH-R13, -Y-Z, C4-10 carbocyclyl, or C1-10 heterocyclyl, wherein C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyl, C1-6 haloalkyl, C1-6 aminoalkyl, C1-6 alkylhydroxy, or C1-10 heterocyclyl is optionally substituted with one or more groups selected from halogen, hydroxyl, amine, C1-6 alkoxy, C3-6 cycloalkyl, C1-6 alkylhydroxy, C1-6 aminoalkyl, C1-6 haloalkoxy, C4-10 carbocyclyl, or C1-10 heterocyclyl, wherein C3-6 cycloalkyl, or C1-6 aminoalkyl, is optionally further substituted with one or more groups independently selected from halogen, hydroxyl, C1-6 alkylhydroxy, -C(O)C1-6 alkyl, -C(O)NH2, -C(O)-C1-6alkylhydroxy, or C1- 10 heterocyclyl, and C1-10 heterocyclyl is optionally substituted with 1 to 3 groups independently selected from halogen, hydroxyl, C1-6 alkyl, C1-6 alkoxy, or C1-6 haloalkoxy; Y is selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, or C3-6 cycloalkenyl; and C1-6 alkyl is optionally substituted with C3-6 cycloalkyl; Z is selected from -OH, -NH2, -COOH, -SO2NH2, -SO2CH3, -SOCH3, -SCH3, CH2-NH-(C1-6 alkyl)-SOCH3, -O-P(=O)(OH)2, -CONH2, -CONH(C1-6 alkyl), -SO2NH(C1-6 alkyl), CON(C1-6 alkyl)2, -NHCO(C1-6 alkyl), C4-10 carbocyclyl, or C1-10 heterocyclyl, wherein C1-10 heterocyclyl has 1 to 4 heteroatoms independently selected from O, N or S, and optionally substituted with 1 to 3 groups independently selected from halogen, C1-6 alkyl, C1-6 alkoxy, or C1-6 haloalkoxy; R13 is selected from hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, or C3-6 halocycloalkyl; R7, R8, R9, and R9a are independently selected from hydrogen, halogen, cyano, C1-6 alkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, or C3-6 halocycloalkyl; and n is 0, 1, or 2. < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00002"> <pat:ClaimNumber>2< / pat:ClaimNumber> <pat:ClaimText>2. The compound as claimed in claim 1, or its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, stereoisomers, and racemates thereof, wherein A is selected from [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] * is the point of attachment. wherein Q is N or CR1, wherein R1 is selected from cyano, hydrogen, halogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 haloalkyl, or C1-6 haloalkoxy; and C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl is optionally substituted with C1-6alkoxy. < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00003"> <pat:ClaimNumber>3< / pat:ClaimNumber> <pat:ClaimText>3. The compound as claimed in claim 1, or its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, stereoisomers, and racemates thereof, wherein A is selected from [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] Q is N or CR1; R1 is selected from cyano, hydrogen, halogen, C1-6 alkyl, or C1-6 alkoxy; R2 is hydrogen or C1-6 alkyl; R3 is hydrogen or C1-6 alkyl; R4 and R5 are independently selected from hydrogen, halogen, cyano, C1-6 alkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkyl, or C1-6 haloalkoxy; wherein C1-6 alkyl optionally substituted with one or more groups selected from C3-6 cycloalkyl, or C1-6 alkoxy; R6 is selected from hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 alkylhydroxy, C1-6 aminoalkyl, -Y-CO-NH-R13, -Y-Z, or C1-10 heterocyclyl, wherein C1-6 alkyl, C3- 6 cycloalkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 aminoalkyl, C1-6 alkylhydroxy, or C1-10 heterocyclyl is optionally substituted with one or more groups selected from halogen, hydroxyl, amine, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 alkylhydroxy, C1-6 aminoalkyl, C1-6 haloalkoxy, or C1-10 heterocyclyl, wherein C3-6 cycloalkyl, or C1-6 aminoalkyl is optionally further substituted with one or more groups independently selected from halogen, hydroxyl, C1-6 alkylhydroxy, -C(O)C1-6 alkyl, - <semantics>C(O)NH2<annotation encoding="application / x-tex">C(O)NH_2< / annotation>< / semantics>, or <semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics>alkylhydroxy; Y is C1-6 alkyl or C3-6 cycloalkyl; Z is selected from -SO2NH2, -SO2CH3, -SOCH3, -SCH3, CH2- NH-(C1-6 alkyl)-SOCH3, -CONH2, -CONH(C1-6 alkyl), -SO2NH(C1-6 alkyl), CON(C1-6 alkyl)2, or -NHCO(C1-6 alkyl); R13 is selected from hydrogen, C1-6 alkyl, or C3-6 cycloalkyl; R7, R8, R9, and R9a are independently selected from hydrogen, halogen, cyano, C1-6 alkyl, C3-6 cycloalkyl, or C1-6 alkoxy; and n is 0, 1 or 2. < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00004"> <pat:ClaimNumber>4< / pat:ClaimNumber> <pat:ClaimText>4. The compound as claimed in any one of the claims 1 to 3, or its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, stereoisomers, and racemates, is selected from a group consisting of: 7-amino-2,3-dimethyl-5-{[1-(6-methylpyridin-2-yl)ethyl]amino}pyrazolo[1,5- a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00002"> <pat:ClaimNumber>2< / pat:ClaimNumber> <pat:ClaimText>2. 7-amino-2,3-dimethyl-5-{[(1S)-1-(6-methylpyridin-2- yl)ethyl]amino}pyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00003"> <pat:ClaimNumber>3< / pat:ClaimNumber> <pat:ClaimText>3. (R)-7-Amino-3-ethyl-2-methyl-5-((1-(pyridin-2-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00004"> <pat:ClaimNumber>4< / pat:ClaimNumber> <pat:ClaimText>4. (S)-7-Amino-3-ethyl-2-methyl-5-((1-(pyridin-2-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00005"> <pat:ClaimNumber>5< / pat:ClaimNumber> <pat:ClaimText>5. (S)-7-Amino-3-ethyl-2-methyl-5-((1-(6-methylpyridin-2-yl) ethyl) amino) pyrazolo [1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00006"> <pat:ClaimNumber>6< / pat:ClaimNumber> <pat:ClaimText>6. 7-amino-2,3-dimethyl-5-{[(6-methylpyridin-2-yl)methyl]amino}pyrazolo[1,5- a pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00007"> <pat:ClaimNumber>7< / pat:ClaimNumber> <pat:ClaimText>7. 7-amino-5-{[(6-ethylpyridin-2-yl)methyl]amino}-2,3-dimethylpyrazolo[1,5- a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00008"> <pat:ClaimNumber>8< / pat:ClaimNumber> <pat:ClaimText>8. 7-amino-2,3-dimethyl-5-{methyl[(6-methylpyridin-2- yl)methyl]amino}pyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00009"> <pat:ClaimNumber>9< / pat:ClaimNumber> <pat:ClaimText>9. 7-amino-5-({[6-(2-hydroxypropan-2-yl)pyridin-2-yl]methyl}amino)-2,3- dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00010"> <pat:ClaimNumber>10< / pat:ClaimNumber> <pat:ClaimText>10. 7-Amino-2,3-dimethyl-5-((2-(5-methylpyridin-2-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00011"> <pat:ClaimNumber>11< / pat:ClaimNumber> <pat:ClaimText>11. 7-amino-5-((2-(5-fluoropyridin-2-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00012"> <pat:ClaimNumber>12< / pat:ClaimNumber> <pat:ClaimText>12. 7-amino-5-((2-(6-methoxypyridin-2-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00013"> <pat:ClaimNumber>13< / pat:ClaimNumber> <pat:ClaimText>13. 7-amino-5-((2-(6-methylpyridin-2-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00014"> <pat:ClaimNumber>14< / pat:ClaimNumber> <pat:ClaimText>14. 7-amino-2,3-dimethyl-5-{[1-(6-methylpyridin-2-yl)propan-2- yl]amino}pyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00015"> <pat:ClaimNumber>15< / pat:ClaimNumber> <pat:ClaimText>15. 7-amino-2,3-dimethyl-5-{[1-(6-methylpyridin-2-yl)propan-2- yl]amino}pyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00016"> <pat:ClaimNumber>16< / pat:ClaimNumber> <pat:ClaimText>16. 7-amino-5-({2-[6-(2-hydroxypropan-2-yl)pyridin-2-yl]ethyl}amino)-2,3- dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00017"> <pat:ClaimNumber>17< / pat:ClaimNumber> <pat:ClaimText>17. 7-Amino-3-ethyl-2-methyl-5-((2-(6-methylpyridin-2-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00018"> <pat:ClaimNumber>18< / pat:ClaimNumber> <pat:ClaimText>18. 7-Amino-3-ethyl-2-methyl-5-((2-(5-methylpyridin-2-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00019"> <pat:ClaimNumber>19< / pat:ClaimNumber> <pat:ClaimText>19. : 7-Amino-3-ethyl-5-((2-(5-methoxypyridin-2-yl) ethyl) amino)-2-methylpyrazolo [1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00020"> <pat:ClaimNumber>20< / pat:ClaimNumber> <pat:ClaimText>20. 7-Amino-3-ethyl-5-((2-(6-methoxypyridin-2-yl) ethyl) amino)-2-methylpyrazolo [1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00021"> <pat:ClaimNumber>21< / pat:ClaimNumber> <pat:ClaimText>21. 7-Amino-3-ethyl-5-((2-(5-fluoropyridin-2-yl) ethyl) amino)-2- methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00022"> <pat:ClaimNumber>22< / pat:ClaimNumber> <pat:ClaimText>22. 7-Amino-3-ethyl-2-methyl-5-((1-(pyridin-2-yl) propan-2-yl) amino) pyrazolo[1,5- a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00023"> <pat:ClaimNumber>23< / pat:ClaimNumber> <pat:ClaimText>23. 7-Amino-3-ethyl-2-methyl-5-((1-(pyridin-2-yl) propan-2-yl) amino) pyrazolo[1,5- a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00024"> <pat:ClaimNumber>24< / pat:ClaimNumber> <pat:ClaimText>24. 7-Amino-3-ethyl-2-methyl-5-((1-(6-methylpyridin-2-yl) propan-2-yl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00025"> <pat:ClaimNumber>25< / pat:ClaimNumber> <pat:ClaimText>25. 7-amino-3-ethyl-5-({2-[6-(2-hydroxypropan-2-yl)pyridin-2-yl]ethyl}amino)-2- methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00026"> <pat:ClaimNumber>26< / pat:ClaimNumber> <pat:ClaimText>26. 7-amino-3-(cyclopropylmethyl)-2-methyl-5-((2-(6-methylpyridin-2-yl)ethyl) amino) pyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00027"> <pat:ClaimNumber>27< / pat:ClaimNumber> <pat:ClaimText>27. 7-amino-3-(isopropylmethyl)-2-methyl-5-((2-(6-methylpyridin-2-yl)ethyl) amino) pyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00028"> <pat:ClaimNumber>28< / pat:ClaimNumber> <pat:ClaimText>28. 7-amino-3-(isopropyl)-2-methyl-5-((2-(6-methylpyridin-2-yl)ethyl) amino) pyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00029"> <pat:ClaimNumber>29< / pat:ClaimNumber> <pat:ClaimText>29. 7-amino-5-{[2-(1-ethyl-1H-pyrazol-3-yl)ethyl]amino}-2,3-dimethylpyrazolo[1,5- a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00030"> <pat:ClaimNumber>30< / pat:ClaimNumber> <pat:ClaimText>30. 7-amino-3-ethyl-5-{[2-(1-ethyl-1H-pyrazol-3-yl)ethyl]amino}-2- methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00031"> <pat:ClaimNumber>31< / pat:ClaimNumber> <pat:ClaimText>31. 7-amino-5-({2-[1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazol-3- yl]ethyl}amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00032"> <pat:ClaimNumber>32< / pat:ClaimNumber> <pat:ClaimText>32. 7-amino-3-ethyl-5-((2-(1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00033"> <pat:ClaimNumber>33< / pat:ClaimNumber> <pat:ClaimText>33. 7-amino-3-chloro-5-((2-(6-(hydroxymethyl) pyridin-2-yl) ethyl) amino)-2- methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00034"> <pat:ClaimNumber>34< / pat:ClaimNumber> <pat:ClaimText>34. 7-amino-3-chloro-5-((2-(6-(1-(hydroxymethyl) cyclopropyl) pyridin-2-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00035"> <pat:ClaimNumber>35< / pat:ClaimNumber> <pat:ClaimText>35. 7-amino-3-chloro-5-((2-(1-(2-hydroxyethyl)-1H-pyrazol-3-yl) ethyl) amino)-2- methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00036"> <pat:ClaimNumber>36< / pat:ClaimNumber> <pat:ClaimText>36. 7-amino-3-chloro-5-((2-(1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00037"> <pat:ClaimNumber>37< / pat:ClaimNumber> <pat:ClaimText>37. 7-amino-3-chloro-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00038"> <pat:ClaimNumber>38< / pat:ClaimNumber> <pat:ClaimText>38. 7-amino-3-chloro-5-((2-(6-(2-(hydroxymethyl) cyclopropyl) pyridin-2-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00039"> <pat:ClaimNumber>39< / pat:ClaimNumber> <pat:ClaimText>39. 7-amino-3-ethyl-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00040"> <pat:ClaimNumber>40< / pat:ClaimNumber> <pat:ClaimText>40. amino-5-((2-(6-ethylpyridin-2-yl) ethyl) amino)-2,3-dimethylpyrazolo [1,5-a] pyrimidine -6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00041"> <pat:ClaimNumber>41< / pat:ClaimNumber> <pat:ClaimText>41. 7-amino-5-((2-(3-fluoro-6-methylpyridin-2-yl) ethyl) amino)-2,3- dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00042"> <pat:ClaimNumber>42< / pat:ClaimNumber> <pat:ClaimText>42. 7-amino-2-ethyl-3-methyl-5-((2-(6-methylpyridin-2-yl) ethyl) amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00043"> <pat:ClaimNumber>43< / pat:ClaimNumber> <pat:ClaimText>43. 7-amino-2-ethyl-5-((2-(6-(2-hydroxypropan-2-yl) pyridin-2-yl)ethyl)amino)-3- methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00044"> <pat:ClaimNumber>44< / pat:ClaimNumber> <pat:ClaimText>44. 7-amino-5-((2-(6-(hydroxymethyl) pyridin-2-yl) ethyl) amino)-2,3- dimethylpyrazolo [1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00045"> <pat:ClaimNumber>45< / pat:ClaimNumber> <pat:ClaimText>45. 7-amino-3-ethyl-5-((2-(6-(hydroxymethyl) pyridin-2-yl) ethyl)amino)-2- methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00046"> <pat:ClaimNumber>46< / pat:ClaimNumber> <pat:ClaimText>46. 7-amino-3-(cyclopropyl methyl)-5-((2-(6-(hydroxymethyl) pyridin-2-yl) ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00047"> <pat:ClaimNumber>47< / pat:ClaimNumber> <pat:ClaimText>47. 7-amino-2-cyclopropyl-5-((2-(6-(2-hydroxypropan-2-yl) pyridin-2-yl) ethyl)amino)-3-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00048"> <pat:ClaimNumber>48< / pat:ClaimNumber> <pat:ClaimText>48. 7-amino-2-(difluoromethyl)-3-ethyl-5-((2-(1-(1-hydroxy-2-methylpropan-2-yl)- 1H-pyrazol-3-yl) ethyl) amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00049"> <pat:ClaimNumber>49< / pat:ClaimNumber> <pat:ClaimText>49. 7-amino-5-((2-(6-(1-(hydroxymethyl) cyclopropyl) pyridin-2-yl) ethyl)amino)- 2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00050"> <pat:ClaimNumber>50< / pat:ClaimNumber> <pat:ClaimText>50. 7-amino-3-ethyl-5-((2-(6-(1-(hydroxymethyl) cyclopropyl) pyridin-2-yl) ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00051"> <pat:ClaimNumber>51< / pat:ClaimNumber> <pat:ClaimText>51. 7-amino-5-((2-(6-(2-(hydroxymethyl) cyclopropyl) pyridin-2-yl) ethyl)amino)- 2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00052"> <pat:ClaimNumber>52< / pat:ClaimNumber> <pat:ClaimText>52. 7-amino-3-ethyl-5-((2-(6-(1-hydroxy-2-methylpropan-2-yl) pyridin-2-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00053"> <pat:ClaimNumber>53< / pat:ClaimNumber> <pat:ClaimText>53. 7-amino-5-((2-(6-(1-hydroxy-2-methylpropan-2-yl) pyridin-2-yl) ethyl) amino)- 2,3-dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00054"> <pat:ClaimNumber>54< / pat:ClaimNumber> <pat:ClaimText>54. 7-amino-3-ethyl-5-((2-(1-(2-hydroxyethyl)-1H-pyrazol-3-yl) ethyl) amino)-2- methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00055"> <pat:ClaimNumber>55< / pat:ClaimNumber> <pat:ClaimText>55. 7-amino-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino)-2,3-dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00056"> <pat:ClaimNumber>56< / pat:ClaimNumber> <pat:ClaimText>56. 7-amino-2-(difluoro methyl)-3-ethyl-5-((2-(6-(hydroxymethyl) pyridin-2-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00057"> <pat:ClaimNumber>57< / pat:ClaimNumber> <pat:ClaimText>57. 7-amino-5-(((1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazol-3-yl) methyl) amino)-2,3-dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00058"> <pat:ClaimNumber>58< / pat:ClaimNumber> <pat:ClaimText>58. 7-amino-2-(difluoro methyl)-3-ethyl-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)- 1H-pyrazol-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00059"> <pat:ClaimNumber>59< / pat:ClaimNumber> <pat:ClaimText>59. 7-amino-2-(difluoro methyl)-3-ethyl-5-((2-(6-(2-(hydroxymethyl) cyclopropyl) pyridin-2-yl) ethyl) amino) pyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00060"> <pat:ClaimNumber>60< / pat:ClaimNumber> <pat:ClaimText>60. 7-amino-3-ethyl-5-((2-(6-(2-(hydroxymethyl) cyclopropyl) pyridin-2-yl) ethyl) amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00061"> <pat:ClaimNumber>61< / pat:ClaimNumber> <pat:ClaimText>61. 7-amino-3-chloro-5-((2-(4-(1-(hydroxymethyl) cyclopropyl) thiazol-2-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00062"> <pat:ClaimNumber>62< / pat:ClaimNumber> <pat:ClaimText>62. 7-amino-3-ethyl-5-((2-(4-fluoro-1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazol- 3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00063"> <pat:ClaimNumber>63< / pat:ClaimNumber> <pat:ClaimText>63. 7-amino-3-ethyl-5-((2-(1-((1-(hydroxymethyl) cyclopropyl) methyl)-1H-pyrazol- 3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00064"> <pat:ClaimNumber>64< / pat:ClaimNumber> <pat:ClaimText>64. 7-amino-3-chloro-5-((2-(6-(1,1-difluoro-2-hydroxyethyl) pyridin-2-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00065"> <pat:ClaimNumber>65< / pat:ClaimNumber> <pat:ClaimText>65. 7-amino-3-chloro-5-((2-(6-(1-hydroxy-2-methylpropan-2-yl) pyridin-2-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00066"> <pat:ClaimNumber>66< / pat:ClaimNumber> <pat:ClaimText>66. 7-amino-3-ethyl-5-((2-(4-(1-(hydroxymethyl) cyclopropyl) thiazol-2-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00067"> <pat:ClaimNumber>67< / pat:ClaimNumber> <pat:ClaimText>67. 7-amino-3-chloro-5-((2-(1-(2-(hydroxymethyl) cyclobutyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00068"> <pat:ClaimNumber>68< / pat:ClaimNumber> <pat:ClaimText>68. 7-amino-5-((2-(1-(1-(amino methyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino)- 3-chloro-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00069"> <pat:ClaimNumber>69< / pat:ClaimNumber> <pat:ClaimText>69. 7-amino-3-bromo-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00070"> <pat:ClaimNumber>70< / pat:ClaimNumber> <pat:ClaimText>70. 7-amino-3-chloro-5-((2-(1-ethyl-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)-2- methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00071"> <pat:ClaimNumber>71< / pat:ClaimNumber> <pat:ClaimText>71. 7-amino-3-ethyl-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00072"> <pat:ClaimNumber>72< / pat:ClaimNumber> <pat:ClaimText>72. 7-amino-3-bromo-5-((2-(6-(hydroxymethyl) pyridine-2-yl) ethyl) amino)-2- methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00073"> <pat:ClaimNumber>73< / pat:ClaimNumber> <pat:ClaimText>73. 7-amino-3-chloro-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-1H-pyrazol-4-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00074"> <pat:ClaimNumber>74< / pat:ClaimNumber> <pat:ClaimText>74. 7-amino-3-(cyclopropyl methyl)-5-((2-(1-(1-(hydroxymethyl) cyclopropyl) -1H- pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00075"> <pat:ClaimNumber>75< / pat:ClaimNumber> <pat:ClaimText>75. 7-amino-3-chloro-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-5-methyl-1H- pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00076"> <pat:ClaimNumber>76< / pat:ClaimNumber> <pat:ClaimText>76. 7-amino-3-ethyl-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-5-methyl-1H-pyrazol- 3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00077"> <pat:ClaimNumber>77< / pat:ClaimNumber> <pat:ClaimText>77. N-((1-(3-(2-((7-amino-3-chloro-6-cyano-2-methylpyrazolo[1,5-a] pyrimidin-5-yl) amino) ethyl)-1H-pyrazol-1-yl) cyclopropyl) methyl) acetamide; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00078"> <pat:ClaimNumber>78< / pat:ClaimNumber> <pat:ClaimText>78. (+)- 7-amino-3-ethyl-5-((2-(1-(2-(hydroxymethyl)cyclobutyl)-1H-pyrazol-3- yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00079"> <pat:ClaimNumber>79< / pat:ClaimNumber> <pat:ClaimText>79. (-) - 7-amino -3-ethyl-5-((2-(1-(2-(hydroxymethyl)cyclobutyl)-1H-pyrazol-3- yl)ethyl) amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00080"> <pat:ClaimNumber>80< / pat:ClaimNumber> <pat:ClaimText>80. 7-amino-3-ethyl-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-5-methyl-1H-pyrazol- 3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00081"> <pat:ClaimNumber>81< / pat:ClaimNumber> <pat:ClaimText>81. 7-amino-3-ethyl-5-((2-(1-(1-hydroxypropan-2-yl)-1H-pyrazol-3-yl) ethyl) amino)- 2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00082"> <pat:ClaimNumber>82< / pat:ClaimNumber> <pat:ClaimText>82. (+-) - 7-amino-3-chloro-5-((2-(1-((3-hydroxycyclobutyl) methyl)-1H-pyrazol-3- yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00083"> <pat:ClaimNumber>83< / pat:ClaimNumber> <pat:ClaimText>83. (+) - 7-amino-3-chloro-5-((2-(1-((3-hydroxycyclobutyl) methyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00084"> <pat:ClaimNumber>84< / pat:ClaimNumber> <pat:ClaimText>84. (-) - 7-amino-3-chloro-5-((2-(1-((3-hydroxycyclobutyl) methyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile(83b); < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00085"> <pat:ClaimNumber>85< / pat:ClaimNumber> <pat:ClaimText>85. 7-amino-3-ethyl-5-((2-(1-((3-hydroxycyclobutyl) methyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00086"> <pat:ClaimNumber>86< / pat:ClaimNumber> <pat:ClaimText>86. 7-amino-5-((2-(1-(1-(hydroxy methyl) cyclopropyl)-5-methyl-1H-pyrazol-3-yl) ethyl) amino)-2,3-dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00087"> <pat:ClaimNumber>87< / pat:ClaimNumber> <pat:ClaimText>87. 7-amino-3-chloro-2-methyl-5-((2-(1-methyl-2-oxo-1,2-dihydropyridin 3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00088"> <pat:ClaimNumber>88< / pat:ClaimNumber> <pat:ClaimText>88. 7-amino-3-ethyl-2-methyl-5-((2-(1-methyl-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00089"> <pat:ClaimNumber>89< / pat:ClaimNumber> <pat:ClaimText>89. 7-amino-3-bromo-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-5-methyl-1H- pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00090"> <pat:ClaimNumber>90< / pat:ClaimNumber> <pat:ClaimText>90. 7-amino-3-chloro-5-((2-(6-(((2-hydroxyethyl) amino) methyl) pyridin-2-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00091"> <pat:ClaimNumber>91< / pat:ClaimNumber> <pat:ClaimText>91. 7-amino-3-ethyl-5-((2-(5-fluoro-6-(hydroxymethyl) pyridine-2-yl) ethyl) amino)- 2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00092"> <pat:ClaimNumber>92< / pat:ClaimNumber> <pat:ClaimText>92. 7-amino-3-chloro-5-((2-(1-(2-methoxyethyl)-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00093"> <pat:ClaimNumber>93< / pat:ClaimNumber> <pat:ClaimText>93. 7-amino-3-chloro-5-((2-(1-(2-hydroxyethyl)-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00094"> <pat:ClaimNumber>94< / pat:ClaimNumber> <pat:ClaimText>94. 7-amino-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methyl-3-(trifluoromethyl) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00095"> <pat:ClaimNumber>95< / pat:ClaimNumber> <pat:ClaimText>95. 7-amino-5-((2-(1-(2-(amino methyl) cyclobutyl)-1H-pyrazol-3-yl) ethyl) amino)- 3-chloro-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00096"> <pat:ClaimNumber>96< / pat:ClaimNumber> <pat:ClaimText>96. 7-amino-3-ethyl-5-((2-(6-(((2-methoxyethyl) amino) methyl) pyridine-2-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00097"> <pat:ClaimNumber>97< / pat:ClaimNumber> <pat:ClaimText>97. 7-amino-3-ethyl-5-((2-(6-(((2-hydroxyethyl) amino) methyl) pyridine-2-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00098"> <pat:ClaimNumber>98< / pat:ClaimNumber> <pat:ClaimText>98. 7-amino-3-chloro-5-((2-(1-(1-(((2-hydroxyethyl) amino) methyl) cyclopropyl)- 1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00099"> <pat:ClaimNumber>99< / pat:ClaimNumber> <pat:ClaimText>99. N-((1-(3-(2-((7-amino-3-chloro-6-cyano-2-methylpyrazolo[1,5-a] pyrimidin-5-yl) amino) ethyl)-1H-pyrazol-1-yl) cyclopropyl) methyl)-3-hydroxypropanamide; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00100"> <pat:ClaimNumber>100< / pat:ClaimNumber> <pat:ClaimText>100. 7-amino-3-ethyl-5-((2-(6-(1-hydroxyethyl) pyridine-2-yl) ethyl) amino)-2- methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00101"> <pat:ClaimNumber>101< / pat:ClaimNumber> <pat:ClaimText>101. 7-amino-3-cyclopropyl-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-1H-pyrazol-3- yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00102"> <pat:ClaimNumber>102< / pat:ClaimNumber> <pat:ClaimText>102. 7-amino-2-(difluoro methyl)-3-ethyl-5-((2-(1-(2-(hydroxymethyl) cyclobutyl)-1H- pyrazol-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00103"> <pat:ClaimNumber>103< / pat:ClaimNumber> <pat:ClaimText>103. (+-)-7-amino-5-((2-(1-(2-(hydroxymethyl) cyclobutyl)-1H-pyrazol-3- yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00104"> <pat:ClaimNumber>104< / pat:ClaimNumber> <pat:ClaimText>104. (+)-7-amino-5-((2-(1-(2-(hydroxymethyl) cyclobutyl) -1H-pyrazol-3- yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile (104a); 104b. (-)-7-amino-5-((2-(1-(2-(hydroxymethyl)cyclobutyl)-1H-pyrazol-3- yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile (104b); < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00105"> <pat:ClaimNumber>105< / pat:ClaimNumber> <pat:ClaimText>105. 7-amino-5-((2-(6-(((2-hydroxyethyl) amino) methyl) pyridin-2-yl) ethyl) amino)- 2,3-dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00106"> <pat:ClaimNumber>106< / pat:ClaimNumber> <pat:ClaimText>106. 7-amino-3-ethyl-5-((2-(1-(1-(((2-hydroxyethyl) amino) methyl) cyclopropyl)-1H- pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00107"> <pat:ClaimNumber>107< / pat:ClaimNumber> <pat:ClaimText>107. 7-amino-3-ethyl-5-((2-(1-(2-methoxyethyl)-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00108"> <pat:ClaimNumber>108< / pat:ClaimNumber> <pat:ClaimText>108. 7-amino-3-ethyl-5-((2-(1-(2-hydroxyethyl)-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00109"> <pat:ClaimNumber>109< / pat:ClaimNumber> <pat:ClaimText>109. 7-amino-5-((2-(1-(2-(amino methyl) cyclobutyl)-1H-pyrazol-3-yl) ethyl) amino)- 3-ethyl-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00110"> <pat:ClaimNumber>110< / pat:ClaimNumber> <pat:ClaimText>110. 7-amino-3-ethyl-5-((2-(1-(3-hydroxypropyl)-1H-pyrazol-5-yl) ethyl) amino)-2- methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00111"> <pat:ClaimNumber>111< / pat:ClaimNumber> <pat:ClaimText>111. 7-amino-3-ethyl-5-((2-(1-(3-hydroxypropyl)-1H-pyrazol-3-yl) ethyl) amino)-2- methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00112"> <pat:ClaimNumber>112< / pat:ClaimNumber> <pat:ClaimText>112. 7-amino-3-chloro-5-((2-(1-(1-(2-hydroxyethyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00113"> <pat:ClaimNumber>113< / pat:ClaimNumber> <pat:ClaimText>113. 7-amino-3-ethyl-5-((2-(1-(3-hydroxypropyl)-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00114"> <pat:ClaimNumber>114< / pat:ClaimNumber> <pat:ClaimText>114. 7-amino-3-chloro-5-((2-(1-(2-(hydroxymethyl) cyclopentyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00115"> <pat:ClaimNumber>115< / pat:ClaimNumber> <pat:ClaimText>115. 7-amino-3-ethyl-5-((2-(1-(2-(hydroxymethyl) cyclopentyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00116"> <pat:ClaimNumber>116< / pat:ClaimNumber> <pat:ClaimText>116. 7-amino-3-(cyclopropyl methyl)-5-((2-(1-(2-(hydroxymethyl) cyclobutyl)-1H- pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00117"> <pat:ClaimNumber>117< / pat:ClaimNumber> <pat:ClaimText>117. 7-amino-3-chloro-5-((2-(1-(2-(((2-hydroxyethyl) amino) methyl) cyclobutyl)-1H- pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00118"> <pat:ClaimNumber>118< / pat:ClaimNumber> <pat:ClaimText>118. 7-amino-5-((2-(1-(2-(amino methyl) cyclopentyl)-1H-pyrazol-3-yl) ethyl) amino)- 3-chloro-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00119"> <pat:ClaimNumber>119< / pat:ClaimNumber> <pat:ClaimText>119. 7-amino-3-chloro-2-methyl-5-((2-(6-methylpyridin-2-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00120"> <pat:ClaimNumber>120< / pat:ClaimNumber> <pat:ClaimText>120. 7-amino-3-chloro-5-((2-(6-ethylpyridin-2-yl) ethyl) amino)-2-methylpyrazolo[1,5- a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00121"> <pat:ClaimNumber>121< / pat:ClaimNumber> <pat:ClaimText>121. (+-)-7-amino-3-ethyl-5-((2-(1-(4-(hydroxymethyl)tetrahydrofuran-3-yl)-1H- pyrazol-3-yl)ethyl)amino)-2-methyl pyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00122"> <pat:ClaimNumber>122< / pat:ClaimNumber> <pat:ClaimText>122. (+)-7-amino-3-ethyl-5-((2-(1-(4-(hydroxy methyl)tetrahydrofuran-3-yl)-1H- pyrazol-3-yl)ethyl)amino)-2-methyl pyrazolo[1,5-a]pyrimidine-6-carbonitrile (122a); 122b. (-)-7-amino-3-ethyl-5-((2-(1-(4-(hydroxy methyl)tetrahydrofuran-3-yl)-1H- pyrazol-3-yl)ethyl)amino)-2-methyl pyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00123"> <pat:ClaimNumber>123< / pat:ClaimNumber> <pat:ClaimText>123. (-)-7-amino-3-ethyl-5-((2-(1-(4-(hydroxy methyl)tetrahydrofuran-3-yl)-1H- pyrazol-3-yl)ethyl)amino)-2-methyl pyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00124"> <pat:ClaimNumber>124< / pat:ClaimNumber> <pat:ClaimText>124. 7-amino-3-ethyl-5-((2-(1-(3-(hydroxymethyl) cyclobutyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00125"> <pat:ClaimNumber>125< / pat:ClaimNumber> <pat:ClaimText>125. 7-amino-3-ethyl-5-((2-(1-(1-(2-hydroxyethyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00126"> <pat:ClaimNumber>126< / pat:ClaimNumber> <pat:ClaimText>126. 7-amino-5-((2-(1-(2-aminoethyl)-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)-3- ethyl-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00127"> <pat:ClaimNumber>127< / pat:ClaimNumber> <pat:ClaimText>127. 7-amino-3-chloro-5-((2-(1-(4-(hydroxymethyl) tetrahydrofuran-3-yl)-1H-pyrazol- 3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00128"> <pat:ClaimNumber>128< / pat:ClaimNumber> <pat:ClaimText>128. 7-amino-3-ethyl-5-((2-(1-((3-hydroxycyclobutyl) methyl)-2-oxo-1,2- dihydropyridin-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00129"> <pat:ClaimNumber>129< / pat:ClaimNumber> <pat:ClaimText>129. 7-amino-5-((2-(1-(3-aminopropyl)-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)- 3-chloro-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00130"> <pat:ClaimNumber>130< / pat:ClaimNumber> <pat:ClaimText>130. 7-amino-3-bromo-5-((2-(1-(2-(hydroxymethyl) cyclobutyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00131"> <pat:ClaimNumber>131< / pat:ClaimNumber> <pat:ClaimText>131. 7-amino-2-(difluoromethyl)-3-ethyl-5-((2-(1-(2-hydroxyethyl)-2-oxo-1,2- dihydropyridin-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00132"> <pat:ClaimNumber>132< / pat:ClaimNumber> <pat:ClaimText>132. (+-)-7-amino-5-((2-(1-(4-(hydroxymethyl) tetrahydrofuran-3-yl)-1H-pyrazol-3-yl) ethyl) amino)-2,3-dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00133"> <pat:ClaimNumber>133< / pat:ClaimNumber> <pat:ClaimText>133. (+)-7-amino-5-((2-(1-(4-(hydroxymethyl) tetrahydrofuran-3-yl)-1H-pyrazol-3-yl) ethyl) amino)-2,3-dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile (133a); 133b. (-)-7-amino-5-((2-(1-(4-(hydroxymethyl) tetrahydrofuran-3-yl)-1H-pyrazol-3-yl) ethyl) amino)-2,3-dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00134"> <pat:ClaimNumber>134< / pat:ClaimNumber> <pat:ClaimText>134. 2-(((2-(3-(2-((7-amino-6-cyano-3-ethyl-2-methylpyrazolo[1,5-a] pyrimidin-5-yl) amino) ethyl)-1H-pyrazol-1-yl) cyclobutyl) methyl) amino) acetamide; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00135"> <pat:ClaimNumber>135< / pat:ClaimNumber> <pat:ClaimText>135. 7-amino-3-ethyl-2-methyl-5-((2-(6-(2,2,2-trifluoro-1-hydroxyethyl) pyridine-2-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6 carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00136"> <pat:ClaimNumber>136< / pat:ClaimNumber> <pat:ClaimText>136. 7-amino-5-((2-(1-(3-aminopropyl)-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)- 3-ethyl-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00137"> <pat:ClaimNumber>137< / pat:ClaimNumber> <pat:ClaimText>137. 7-amino-3-(cyclo butyl methyl)-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-1H- pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00138"> <pat:ClaimNumber>138< / pat:ClaimNumber> <pat:ClaimText>138. 7-amino-5-((2-(1-(3-hydroxypropyl)-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)-2,3-dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00139"> <pat:ClaimNumber>139< / pat:ClaimNumber> <pat:ClaimText>139. 7-amino-3-ethyl-5-((2-(6-(2-hydroxyethyl) pyridine-2-yl) ethyl) amino)-2- methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00140"> <pat:ClaimNumber>140< / pat:ClaimNumber> <pat:ClaimText>140. 7-amino-2,3-dimethyl-5-((2-(6-methylpyrazin-2-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00141"> <pat:ClaimNumber>141< / pat:ClaimNumber> <pat:ClaimText>141. 7-amino-5-((2-(1-(3-aminopropyl)-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)- 2,3-dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00142"> <pat:ClaimNumber>142< / pat:ClaimNumber> <pat:ClaimText>142. 7-amino-3-ethyl-2-methyl-5-((2-(1-(2-(methylthio) ethyl)-2-oxo-1,2- dihydropyridin-3-yl) ethyl) amino) pyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00143"> <pat:ClaimNumber>143< / pat:ClaimNumber> <pat:ClaimText>143. (+-)7-amino-3-ethyl-2-methyl-5-((2-(1-(2-(methyl sulfinyl) ethyl)-2-oxo-1,2- dihydropyridin-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; 144a. (+)7-amino-3-ethyl-2-methyl-5-((2-(1-(2-(methyl sulfinyl) ethyl)-2-oxo-1,2- dihydropyridin-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; 144b. (-)7-amino-3-ethyl-2-methyl-5-((2-(1-(2-(methyl sulfinyl) ethyl)-2-oxo-1,2- dihydropyridin-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00145"> <pat:ClaimNumber>145< / pat:ClaimNumber> <pat:ClaimText>145. N-(3-(3-(2-((7-amino-6-cyano-3-ethyl-2-methylpyrazolo[1,5-a] pyrimidin-5-yl) amino) ethyl)-2-oxopyridin-1(2H)-yl) propyl) acetamide; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00146"> <pat:ClaimNumber>146< / pat:ClaimNumber> <pat:ClaimText>146. 7-amino-5-((2-(1-(1-(amino methyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino)- 3-ethyl-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00147"> <pat:ClaimNumber>147< / pat:ClaimNumber> <pat:ClaimText>147. N-((1-(3-(2-((7-amino-6-cyano-3-ethyl-2-methylpyrazolo[1,5-a] pyrimidin-5-yl) amino) ethyl)-1H-pyrazol-1-yl) cyclopropyl) methyl) acetamide; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00148"> <pat:ClaimNumber>148< / pat:ClaimNumber> <pat:ClaimText>148. 7-amino-5-((2-(1-(1-(2-aminoethyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino)- 3-ethyl-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00149"> <pat:ClaimNumber>149< / pat:ClaimNumber> <pat:ClaimText>149. N-(2-(1-(3-(2-((7-amino-6-cyano-3-ethyl-2-methylpyrazolo[1,5-a] pyrimidin-5-yl) amino) ethyl)-1H-pyrazol-1-yl) cyclopropyl) ethyl) acetamide; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00150"> <pat:ClaimNumber>150< / pat:ClaimNumber> <pat:ClaimText>150. 7-amino-3-ethyl-5-((2-(6-(2-hydroxyethoxy) pyridine-2-yl) ethyl) amino)-2- methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00151"> <pat:ClaimNumber>151< / pat:ClaimNumber> <pat:ClaimText>151. 7-amino-5-((2-(1-(1-(2-aminoethyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino)- 3-chloro-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00152"> <pat:ClaimNumber>152< / pat:ClaimNumber> <pat:ClaimText>152. 7-amino-5-((2-(6-(2-hydroxyethyl) pyridine-2-yl) ethyl) amino)-2,3- dimethylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00153"> <pat:ClaimNumber>153< / pat:ClaimNumber> <pat:ClaimText>153. 7-amino-3-ethyl-2-methyl-5-((2-(1-(3-(methylthio) propyl)-2-oxo-1,2- dihydropyridin-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00154"> <pat:ClaimNumber>154< / pat:ClaimNumber> <pat:ClaimText>154. (-)-7-amino-3-ethyl-2-methyl-5-((2-(1-(3-(methyl sulfinyl) propyl)-2-oxo-1,2- dihydropyridin-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile (154a); 154b. (+)-7-amino-3-ethyl-2-methyl-5-((2-(1-(3-(methyl sulfinyl) propyl)-2-oxo-1,2- dihydropyridin-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00155"> <pat:ClaimNumber>155< / pat:ClaimNumber> <pat:ClaimText>155. 7-amino-3-ethyl-5-((2-(6-(3-hydroxypropyl) pyridin-2-yl) ethyl) amino)-2- methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00156"> <pat:ClaimNumber>156< / pat:ClaimNumber> <pat:ClaimText>156. 7-amino-5-((2-(1-(3-hydroxypropyl)-2-oxo-1,2-dihydropyridin-3-yl) ethyl) amino)-2-methyl-3-propylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00157"> <pat:ClaimNumber>157< / pat:ClaimNumber> <pat:ClaimText>157. 7-amino-5-((2-(6-(hydroxymethyl) pyridine-2-yl) ethyl) amino)-2-methyl-3- propylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00158"> <pat:ClaimNumber>158< / pat:ClaimNumber> <pat:ClaimText>158. 7-amino-5-((2-(1-(1-(hydroxymethyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methyl-3-propylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00159"> <pat:ClaimNumber>159< / pat:ClaimNumber> <pat:ClaimText>159. (+)-7-amino-3-ethyl-5-((2-(6-(1-hydroxyethyl) pyridin-2-yl) ethyl) amino)-2- methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile (159a); 159b. (-)-7-amino-3-ethyl-5-((2-(6-(1-hydroxyethyl) pyridine-2-yl) ethyl) amino)-2- methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00160"> <pat:ClaimNumber>160< / pat:ClaimNumber> <pat:ClaimText>160. (+) 7-amino-5-((2-(1-(4-(hydroxymethyl) tetrahydrofuran-3-yl)-1H-pyrazol-3-yl) ethyl) amino)-2-methyl-3-propylpyrazolo[1,5-a] pyrimidine-6-carbonitrile (160a); 160a. (-) 7-amino-5-((2-(1-(4-(hydroxymethyl) tetrahydrofuran-3-yl)-1H-pyrazol-3-yl) ethyl) amino)-2-methyl-3-propylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00161"> <pat:ClaimNumber>161< / pat:ClaimNumber> <pat:ClaimText>161. 7-amino-3-ethyl-2-methyl-5-((2-(1-(3-(methylthio) propyl)-1H-pyrazol-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00162"> <pat:ClaimNumber>162< / pat:ClaimNumber> <pat:ClaimText>162. (-)-7-amino-3-ethyl-2-methyl-5-((2-(1-(3-(methyl sulfinyl) propyl)-1H-pyrazol-3- yl) ethyl) amino) pyrazolo[1,5-a]pyrimidine-6-carbonitrile (162a); 162b. (+)-7-amino-3-ethyl-2-methyl-5-((2-(1-(3-(methylsulfinyl)propyl)-1H-pyrazol-3- yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00163"> <pat:ClaimNumber>163< / pat:ClaimNumber> <pat:ClaimText>163. (-)- 7-amino-3-ethyl-2-methyl-5-((2-(1-(1-(((2-(methyl sulfinyl) ethyl) amino) methyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6- carbonitrile (163a); 163b. (+)-7-amino-3-ethyl-2-methyl-5-((2-(1-(1-(((2-(methyl sulfinyl) ethyl) amino) methyl) cyclopropyl)-1H-pyrazol-3-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6- carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00164"> <pat:ClaimNumber>164< / pat:ClaimNumber> <pat:ClaimText>164. 7-amino-2-methyl-5-((2-(6-methylpyridin-2-yl) ethyl) amino)-3- propylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00165"> <pat:ClaimNumber>165< / pat:ClaimNumber> <pat:ClaimText>165. (+)-7-amino-5-((2-(1-(2-(hydroxymethyl) cyclobutyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methyl-3-propylpyrazolo[1,5-a] pyrimidine-6-carbonitrile (165a); 165b. (-)-7-amino-5-((2-(1-(2-(hydroxymethyl) cyclobutyl)-1H-pyrazol-3-yl) ethyl) amino)-2-methyl-3-propylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00166"> <pat:ClaimNumber>166< / pat:ClaimNumber> <pat:ClaimText>166. (R)-7-amino-3-ethyl-2-methyl-5-((2-(6-(((tetrahydrofuran-3-yl) oxy) methyl) pyridine-2-yl) ethyl) amino) pyrazolo[1,5-a] pyrimidine-6-carbonitrile; < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00167"> <pat:ClaimNumber>167< / pat:ClaimNumber> <pat:ClaimText>167. (-)-7-amino-3-ethyl-5-((2-(1-(4-(hydroxymethyl) tetrahydrofuran-3-yl)-5-methyl- 1H-pyrazol-3-yl) ethyl) amino)-2-methylpyrazolo[1,5-a] pyrimidine-6-carbonitrile; and < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00168"> <pat:ClaimNumber>168< / pat:ClaimNumber> <pat:ClaimText>168. (+)-7-amino-3-ethyl-5-((2-(1-(4-(hydroxy methyl) tetrahydrofuran-3-yl)-1H- pyrazol-3-yl) ethyl) amino)-2-methyl pyrazolo[1,5-a] pyrimidine-6-carbonitrile. < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00005"> <pat:ClaimNumber>5< / pat:ClaimNumber> <pat:ClaimText>5. The compound as claimed in any one of the claims 1 to 4 or its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, stereoisomers, and racemates thereof, for use as a medicament. < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00006"> <pat:ClaimNumber>6< / pat:ClaimNumber> <pat:ClaimText>6. The compound as claimed in any one of the claims 1 to 4, its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, stereoisomers, and racemates thereof for use as an antagonist of adenosine 2a receptor (A2aR) or adenosine 2b receptor (A2bR) or combination of adenosine 2a receptor (<semantics>A2aR<annotation encoding="application / x-tex">A_{2a}R< / annotation>< / semantics>) and adenosine 2b receptor (<semantics>A2bR<annotation encoding="application / x-tex">A_{2b}R< / annotation>< / semantics>). < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00007"> <pat:ClaimNumber>7< / pat:ClaimNumber> <pat:ClaimText>7. The compound as claimed in any one of the claims 1 to 4, its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, stereoisomers, and racemates thereof, for use in treating a disease, disorder or condition selected from cancer, parkinson's disease, asthma, diabetes, and autoimmune disease mediated at least in part by adenosine 2a receptor (A2aR), or adenosine 2b receptor (<semantics>A2bR<annotation encoding="application / x-tex">A_{2b}R< / annotation>< / semantics>), or combination of <semantics>A2aR<annotation encoding="application / x-tex">A_{2a}R< / annotation>< / semantics> and <semantics>A2bR<annotation encoding="application / x-tex">A_{2b}R< / annotation>< / semantics>. < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00008"> <pat:ClaimNumber>8< / pat:ClaimNumber> <pat:ClaimText>8. A process of preparation of compounds of Formula I as claimed in any one of the claims 1 to 4, its pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, stereoisomers, and racemates thereof, said process comprising: reacting Formula (A), and Formula (B) in the presence of a base to obtain the compounds of Formula I, [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] wherein R is selected from C1-6 alkyl, C3-6 cycloalkyl, C5-10 aryl, C2-10 heteroaryl, or C1-10 heterocyclyl; and the substituents are as defined in claim 1. < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00009"> <pat:ClaimNumber>9< / pat:ClaimNumber> <pat:ClaimText>9. The process as claimed in claim 8, wherein the base is selected from triethylamine, diisopropylethylamine, pyridine, sodium carbonate, potassium carbonate, sodium hydroxide, potassium tertiarybutoxide potassium tertiarybutoxide, sodium hydride, lithium bis(trimethylsilyl)amide (LiHMDS), N-diisopropylethylamine, or combinations thereof. < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00010"> <pat:ClaimNumber>10< / pat:ClaimNumber> <pat:ClaimText>10. The process as claimed in claim 8, wherein the process is carried out in the presence of a solvent selected from isopropanol, methanol, n-butanol, dichloromethane, tetrahydrofuran, dimethylformaide, n-methylpyrrolidone, Dimethyl sulfoxide, water, dioxane, acetonitrile, or combinations thereof. < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00011"> <pat:ClaimNumber>11< / pat:ClaimNumber> <pat:ClaimText>11. A pharmaceutical composition comprising compounds of Formula I as claimed in any one of the claims 1 to 4 and one or more additional therapeutic agent. < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00012"> <pat:ClaimNumber>12< / pat:ClaimNumber> <pat:ClaimText>12. The pharmaceutical composition as claimed in claim 11, wherein the one or more additional therapeutic agent is chemotherapeutic agent or immune checkpoint inhibitors; the chemotherapeutic agent is selected from phosphoinositide 3-kinase inhibitor (PI3K) inhibitor, tyrosine kinase inhibitor, signal transducer and activator of transcription 3 (Stat-3) inhibitor, topoisomerase inhibitors, Protein kinase B (AKT) inhibitor, c-Jun N-terminal kinase (JNK1 / K2) inhibitors, hypoxia-inducible factor 1 alpha (HIF-1a) inhibitor, extracellular signal-regulated kinase (ERK) inhibitor, poly ADP ribose polymerase -1( (PARP-1) inhibitor, cisplatin, or oxaplatin; and the immune checkpoint inhibitor is selected from programmed death-1 (PD-1) inhibitor, programmed death-ligand 1 (PD-L1) inhibitor, anti-PD1 antibody, anti-PD-L1 antibody, cytotoxic T-lymphocyte-associated protein 4 (CTLA4)inhibitor, anti-CTLA4 antibody, T cell immunoglobulin and ITIM domain (TIGIT) inhibitor, ecto-nucleoside triphosphate diphosphohydrolase 1(E-NTPDase, CD39) inhibitor, or ecto-5'-nucleotidase(Ecto5'NTase, CD79) inhibitor. < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00013"> <pat:ClaimNumber>13< / pat:ClaimNumber> <pat:ClaimText>13. Use of a therapeutically effective amount of the compound of Formula I as claimed in any one of claims 1 to 4 or the pharmaceutical composition as claimed in claim 11 or 12 in the manufacture of a medicament for treatment of a condition mediated by adenosine receptor or a proliferative disorder or cancer. < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00014"> <pat:ClaimNumber>14< / pat:ClaimNumber> <pat:ClaimText>14. Use of a therapeutically effective amount of the compound of Formula I as claimed in any one of claims 1 to 4 or the pharmaceutical composition as claimed in claim 11 or 12 for administration to a subject suffering from a condition mediated by adenosine receptor or a disease or proliferative disorder or cancer. < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00015"> <pat:ClaimNumber>15< / pat:ClaimNumber> <pat:ClaimText>15. The use as claimed in claim 13 or 14, wherein the disease or disorder or condition is mediated at least in part by adenosine 2a receptor (A2aR), adenosine 2b receptor (A2bR), or combinations thereof. < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00016"> <pat:ClaimNumber>16< / pat:ClaimNumber> <pat:ClaimText>16. The use as claimed in claim 15, wherein the compound of Formula (I) is to be administered in an effective amount to reverse or stop the progression of either the adenosine 2a receptor (<semantics>A2aR<annotation encoding="application / x-tex">A_{2a}R< / annotation>< / semantics>) or adenosine 2b receptor <semantics>(A2aR)<annotation encoding="application / x-tex">(A_{2a}R)< / annotation>< / semantics> or both mediated immunosuppression. < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00017"> <pat:ClaimNumber>17< / pat:ClaimNumber> <pat:ClaimText>17. The use as claimed in claim 13 or 14, wherein said disease, disorder or condition is cancer or an immune response related disease, disorder, or condition. < / pat:ClaimText> < / pat:Claim> <pat:Claim com:id="CLM-00018"> <pat:ClaimNumber>18< / pat:ClaimNumber> <pat:ClaimText>18. The use as claimed in claim 17, wherein said cancer is of adrenal gland, brain, bladder, breast, bone, colon, endometrial, oesophagus, head, gastric, kidney, liver, lung, mouth, muscle, neck, pancreas, prostate, retinal, skin, thyroid or white blood cells and said immune related disease, disorder or condition is selected from the group consisting of allergies, alzheimer, asthma, crohn's disease, colitis, chronic obstructive pulmonary disease, diabetic kidney disorders, glaucoma, lupus, rheumatoid arthritis, multiple sclerosis, pain, panic disorder, pancreatitis, parkinson disease, psoriasis, systemic sclerosis, and ulcerative colitis. < / pat:ClaimText> < / pat:Claim> < / pat:Claims>