Nickel-based catalysts, process for the preparation and application thereof

Abstract

The present invention realtes to a pincer ligated nickel based catalyst of formula I, process of preparation of said pincer ligated nickel based catalyst of formula I. The invention further relates to a process of preparation of C-6 alkylated pyridones and compounds related thereof of formula II by reacting pyridinone and R-halide in presence of said nickel catalyst of formula I.

Description

[0001] NICKEL-BASED CATALYSTS, PROCESS FOR THE PREPARATION AND APPLICA HEREOF

[0002] FIELD OF THE INVENTION

[0003] The present disclosure generally relates to nickel-based catalysts, process for the preparation and application thereof. More particularly, the present invention realtes to a pincer ligated nickel based catalyst of formula I, and a process for the preparation of said pincer ligated nickel based catalyst of formula I. The invention further relates to a process of preparation of C-6 alkylated pyridones and compounds related thereof of formula II by reacting pyridinone and R-halide in the presence of said nickel catalyst of formula I.

[0004] BACKGROUND OF THE INVENTION

[0005] Alkylated 2-pyridones are important chemical moiety as it is a part of many biologically important compounds and natural products, such as ciclopirox, milrinone, A58365A, and sophoramine. These compounds have traditionally been synthesized using rhodium catalysts and alkyl carboxylic acids or anhydrides as coupling partners. But, these traditional synthetic processes are very costly due to involvement of costly catalyst and reagents. Moreover, the complex catalysts includes metals like rhodium, which are not easily available. In addition to this high cost catalyst, these processes do not give good yields of final product alkylated 2-pyridones.

[0006] Few reports are available which provide Ni catalyst for similar coupling reaction such as article entitled “Recent advances in pincer-nickel catalyzedreactions” by Vinay Arora et al., Dalton Trans., 2021, 50, 3394-3428, which reports a glimpse of recent developments in the chemistry of pincer-nickel catalyzedreactions and the applicability of pincer-nickel complexes in catalyzingcross-coupling reactions, oxidation reactions, (de)hydrogenation reactions, dehydrogenativecoupling, hydrosilylation, hydroboration, C-H activation and carbon dioxide functionalization from synthesis and mechanistic points of view. However, the document does not provide a hybrid PNN-ligated system, which has both the hard donor nitrogen and soft-donor phosphine backbones. This unique feature enables the catalyst to show unique activity for the coupling of challenging alkyl chlorides with pyridones. These prior arts have synthesized arene -based NNN, NNP, PNP, and PCP types of pincer complexes. However, the alkylation reactic ’idones is not successful using these pincer complexes, and no reports exist on this reaction with these pincer complexes.

[0007] Thus, there is a need in the art to develop Ni-based pincer catalyst for the alkylation reaction of pyridinones.

[0008] OBJECTIVES OF THE INVENTION

[0009] Main objective of the present invention is to provide a pincer ligated nickel based catalyst of formula I.

[0010] Another objective of the present invention is toprovide a process for the preparation of said pincer ligated nickel based catalyst of formula I.

[0011] Yet another ojective of the present invention is to provide a process of preparation of C-6 alkylated pyridones and compounds related thereof of formula II by reacting pyridinone and R-halide in presence of said nickel catalyst of formula I.

[0012] SUMMARY OF THE INVENTION

[0013] Accordiingly, in order to accomplish an objective, the present invention provides a pincer ligated nickel based catalyst of formula I.

[0014] In an aspect, the present invention provides a pincer ligated nickel based catalyst of formula I, represented as: wherein

[0015] R1and R2are selected from (un)substituted aryl, benzyl, alkyl, and cyclo-alkyl; optionally R1and R2together with P may form a 5-6 membered saturated or unsaturated cyclic ring; R3, R4, R5, R6, R7, R8, R9, R10, R11and R12are selected from hydrogen, (un)substituted alkyl, (un)substituted cyclo-alkyl, alkoxy, and (ui uted aryl; and

[0016] X is selected from chloro, bromo, iodo, OAc, and OTf.

[0017] In an embodiment, the alkyl is selected from propyl, iso-propyl, butyl, and ter-butyl.

[0018] In another aspect, the present invention provides a process for the preparation of said pincer ligated nickel based catalyst of formula I, comprising the steps of: a) mixing (un)substituted A-(2-fluoro-aryl)quinolinyl-amine compound and potassium salt of PR’R2under argon atmosphere followed by heating the mixture at a temperature in the range of 140-160°C for a time period in the range of 5-6 days obtaining crude product, and followed by dilution with solvent, evaporation and purification of crude product to afford (QNNPR1R2)-H compound of formula 1 as a yellow solid; and b) mixing the compound 1 obtained at step a) with Ni(X)2, organic base in a solvent and heating at a temperature in the range of 65-70°C for a time period in the range of 5-6 hr followed by extraction with solvent, evaporation and separation of solid, filtering, washing and drying to afford pincer ligated nickel based catalyst of formula I.

[0019] In yet another aspect, the present invention provides a process for the preparation of C-6 alkylated pyridones and compounds related thereof of formula II by reacting pyridinone and R-halide in presence of said nickel catalyst of formula I. The compound of formula II is represented as:

[0020] Wherein

[0021] R is seleced from (un)substituted alkyl, (un)substituted aryl, (un)substituted heteroaryl, (un)substituted alkoxy, halo, nitro, trifluoromethyl, (un)substituted alkynyl, (un)substituted alkylene, (un)substituted allyl, (un)substituted cyclic ring, cycloalkyl, heteroalkylene, arylalkyl, heterocycloalkyl, heteroarylalkyl, alkylheteroaryl, haloalkyl, heteroalkyl, alkylamino, alkoxycarbonyl, alkylcarb tlkylcarbonylamino, alkylsulfonylamino, aminosulfonyl, alkylaminosulfonyl, dialkylamino sulfonyl, aminosulfonylamino, aminocarbonylamino, alkylaminosulfonylamino, dialkylaminosulfonylamino, alkylaminocarbonylamino, alkylcarbamoyl, thio, alkylthio, alkylsulfinyl, alkylsulfonyl, carbamyl, cyano-alkyl, alkoxyalkyl, dialkylamino, dialkylcarbamyl, haloalkoxy, haloalkyl, ester, ether, acetal, thioacetal, ketal, thioketal, carbamyl, and carbonyl; and

[0022] R13, R14, R15, R16, R17, R18and R19are selected from hydrogen, (un)substituted alkyl, (un)substituted aryl, (un)substituted heteroaryl, (un)substituted alkoxy, halo, nitro, trifluoromethyl, (un)substituted alkynyl, (un) substituted alkylene, (un)substituted allyl, (un)substituted cyclic ring, cycloalkyl, heteroalkylene, arylalkyl, heterocycloalkyl, heteroarylalkyl, alkylheteroaryl, haloalkyl, heteroalkyl, alkylamino, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, alkylsulfonylamino, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, aminosulfonylamino, aminocarbonylamino, alkylamino sulfonylamino, dialkylaminosulfonylamino, alkylaminocarbonylamino, alkylcarbamoyl, thio, alkylthio, alkylsulfinyl, alkylsulfonyl, carbamyl, cyano-alkyl, alkoxyalkyl, dialkylamino, dialkylcarbamyl, haloalkoxy, haloalkyl, ester, ether, acetal, thioacetal, ketal, thioketal, carbamyl, and carbonyl.

[0023] The process for the prearation of C-6 alkylated pyridones and compounds related thereof of formula II comprises the steps of: i. heating a reaction mixture comprising a compound of formula A, a compound of formula B, the catalyst of formula I and a base in a solvent at a temperature in the range of 120-140°C for a time period in the range of 23-25 hr; ii. quenching the reaction mixture obtained at step i) and extracting it with solvent to obtain organic extract; iii. drying and evaporating the organic extract obtained at step ii) under vacuum to obtain a residue; and iv. purifying the residue obtained at step iii) by column chromatography to afford compound of formula II; wherein compound of formula A and compound of formula B in step i) are represented as; wherein

[0024] R is seleced from (un)substituted alkyl, (un)substituted aryl, (un)substituted heteroaryl, (un)substituted alkoxy, halo, nitro, trifluoromethyl, (un)substituted alkynyl, (un)substituted alkylene, (un)substituted allyl, (un)substituted cyclic ring, cycloalkyl, heteroalkylene, arylalkyl, heterocycloalkyl, heteroarylalkyl, alkylheteroaryl, haloalkyl, heteroalkyl, alkylamino, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, alkylsulfonylamino, aminosulfonyl, alkylaminosulfonyl, dialkylamino sulfonyl, aminosulfonylamino, aminocarbonylamino, alkylaminosulfonylamino, dialkylaminosulfonylamino, alkylaminocarbonylamino, alkylcarbamoyl, thio, alkylthio, alkylsulfinyl, alkylsulfonyl, carbamyl, cyano-alkyl, alkoxyalkyl, dialkylamino, dialkylcarbamyl, haloalkoxy, haloalkyl, ester, ether, acetal, thioacetal, ketal, thioketal, carbamyl, and carbonyl; and

[0025] R13, R14, R15, R16, R17, R18, and R19, are selected from hydrogen, (un) substituted alkyl, (un)substituted aryl, (un)substituted heteroaryl, (un)substituted alkoxy, halo, nitro, trifluoromethyl, (un)substituted alkynyl, (un) substituted alkylene, (un)substituted allyl, (un)substituted cyclic ring, cycloalkyl, heteroalkylene, arylalkyl, heterocycloalkyl, heteroarylalkyl, alkylheteroaryl, haloalkyl, heteroalkyl, alkylamino, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, alkylsulfonylamino, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, amino sulfonylamino, aminocarbonylamino, alkylamino sulfonylamino, dialkylaminosulfonylamino, alkylaminocarbonylamino, alkylcarbamoyl, thio, alkylthio, alkylsulfinyl, alkylsulfonyl, carbamyl, cyano-alkyl, alkoxyalkyl, dialkylamino, dialkylcarbamyl, haloalkoxy, haloalkyl, ester, ether, acetal, thioacetal, ketal, thioketal, carbamyl, and carbonyl; and

[0026] X is selected from OAc, Cl, Br, I, F, OTf.

[0027] BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 illustrates the single crystal XRD of the catalyst compound 2a.

[0029] DETAILED DESCRIPTION OF THE INVENTION The compounds described herein can be asymmetric (e.g,, having one or more stereocenters). All stereoisomers, such as enantiomers t tereomers, are intended unless otherwise indicated. Compounds of the present invention that contain asymmetrically substituted carbon atoms can be isolated in optically active or racemic forms. Methods on how to prepare optically active forms from optically inactive starting materials are known in the art; such as by resolution of racemic mixtures or by stereoselective synthesis. Many geometric isomers of olefins, C==N double bonds, and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention.

[0030] Compounds of the invention also include tautomeric forms. Tautomeric Conns result from the swapping of a single bond with an adjacent double bond together with the concomitant migration of a proton. Tautomeric forms include prototropic tautomers which are isomeric protonation states having the same empirical formula and total charge. Tautomeric forms can be in equilibrium or sterically locked into one form by appropriate substitution.

[0031] Compounds of invention can also include all isotopes of atoms occurring in intermediates or final compounds. Isotopes include those atoms having the same atomic number but different mass numbers. For example, isotopes of hydrogen include tritium and deuterium.

[0032] In some embodiments, the compounds of the invention, or salts thereof, are substantially isolated.

[0033] In an embodiment, the present invention provides a pincer ligated nickel based catalyst of formula I, represented as: wherein

[0034] R1and R2are selected from (un)substituted aryl, benzyl, alkyl, and cyclo-alkyl; optionally R1and R2together with P may form a 5-6 membered saturated or unsaturated cyclic ring; R3, R4, R5, R6, R7, R8, R9, R10, R11and R12are selected from hydrogen, (un)substituted alkyl, (un)substituted cyclo-alkyl, alkoxy, and (ui uted aryl; and

[0035] X is selected from chloro, bromo, iodo, OAc, and OTf.

[0036] In an embodiment, the alkyl is selected from propyl, iso-propyl, butyl, and ter-butyl.

[0037] In another embodiment, the present invention provides a process for the preparation of said pincer ligated nickel based catalyst of formula I, wherein the process comprises the steps of: a) mixing (un)substituted A-(2-fluoro-aryl)quinolinyl-amine compound of formula D and potassium salt of PR1R2under argon atmosphere and heating the reaction mixture at a temperature in the range of 140-160°C for a time period in the range of 5-6 days to obtain crude product, followed by diluting the crude product with a solvent, evaporating and purifiying to afford (QNNPR1R2)-H compound of formula 1 as a yellow solid

[0038] Compound D Compound 1 ; and b) mixing the compound 1 obtained at step a) with Ni(X)2, an organic base in a solvent and heating at a temperature in the range of 65-70°C for a time period in the range of 5-6 hr followed by extraction using extraction solvent, evaporation and separation of solid using precipitation inducing solvent, filtering, washing and drying to afford pincer ligated nickel based catalyst of formula I.

[0039] In an embodiment, the solvent used at step a) is selected from ethyl acetate, propyl actetate, isopropyl cetate, butyl acetate, isobutyl acetate, di-tert-butyl ether, di(propylene glycol) methyl ether, dibutyl ether, diethyl ether, diisopropyl ether, dimethoxyethane, dimethoxymethane, 1,4-dioxane, tetrahydrofuran, toluene, and xylene, or any of mixtures thereof.

[0040] In an embodiment, the solvent used in step b) is selected from tetrahydrofuran, toluene, xylene, benzene, hexane, cyclohexane, ethyl acetate, butyl acetate, and isopropyl acetate, or any of mixtures thereof. In an embodiment, the organic base is selected from triethylamine (Et3N), DIPEA (N,N- diisopropylethylamine), DBU (1,8-Diazabi 4.0]undec-7-ene), pyridine, and guanidine.

[0041] In an embodiment, the extraction solvent is selected from ethyl acetate, propyl actetate, isopropyl cetate, butyl acetate, isobutyl acetate, di-tert-butyl ether, di(propylene glycol) methyl ether, dibutyl ether, diethyl ether, diisopropyl ether, dimethoxyethane, dimethoxymethane, 1,4-dioxane, tetrahydrofuran, toluene, and xylene, or any of mixtures thereof.

[0042] In an embodiment, the precipitation inducing solvent is hexane.

[0043] In yet another embodiment, the present invention provides a process for the preparation of C- 6 alkylated pyridones and compounds related thereof of formula II by reacting pyridinone and R-halide in presence of said nickel catalyst of formula I. The compound of formula II is represented as: wherein

[0044] R is seleced from (un)substituted alkyl, (un)substituted aryl, (un)substituted heteroaryl, (un)substituted alkoxy, halo, nitro, trifluoromethyl, (un)substituted alkynyl, (un)substituted alkylene, (un)substituted allyl, (un)substituted cyclic ring, cycloalkyl, heteroalkylene, arylalkyl, heterocycloalkyl, heteroarylalkyl, alkylheteroaryl, haloalkyl, heteroalkyl, alkylamino, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, alkylsulfonylamino, aminosulfonyl, alkylaminosulfonyl, dialkylamino sulfonyl, aminosulfonylamino, aminocarbonylamino, alkylaminosulfonylamino, dialkylaminosulfonylamino, alkylaminocarbonylamino, alkylcarbamoyl, thio, alkylthio, alkylsulfinyl, alkylsulfonyl, carbamyl, cyano-alkyl, alkoxyalkyl, dialkylamino, dialkylcarbamyl, haloalkoxy, haloalkyl, ester, ether, acetal, thioacetal, ketal, thioketal, carbamyl, and carbonyl; and

[0045] R13, R14, R15, R16, R17, R18and R19are selected from hydrogen, (un)substituted alkyl, (un)substituted aryl, (un)substituted heteroaryl, (un)substituted alkoxy, halo, nitro, trifluoromethyl, (un)substituted alkynyl, (un) substituted alkylene, (un)substituted allyl, (un)substituted cyclic ring, cycloalky roalkylene, arylalkyl, heterocycloalkyl, heteroarylalkyl, alkylheteroaryl, haloalkyl, heteroalkyl, alkylamino, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, alkylsulfonylamino, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, aminosulfonylamino, aminocarbonylamino, alkylamino sulfonylamino, dialkylaminosulfonylamino, alkylaminocarbonylamino, alkylcarbamoyl, thio, alkylthio, alkylsulfinyl, alkylsulfonyl, carbamyl, cyano-alkyl, alkoxyalkyl, dialkylamino, dialkylcarbamyl, haloalkoxy, haloalkyl, ester, ether, acetal, thioacetal, ketal, thioketal, carbamayl, and carbonyl.

[0046] In an embodiment, the process for the preparation of said C-6 alkylated pyridones and compounds related thereof of formula II, comprises the process steps of: i. heating the reaction mixture containing a compound of formula A, a compound of formula B, the catalyst of formula I and a base in a solvent at a temperature in the range of 120-140°C for a time period in the range of 23-25 hr; ii. quenching and extracting the reaction mixture obtained at step i) using an organic solvent to obtain organic extract; iii. drying and evaporating the organic extract obtained at step ii) under vacuum to obtain a residue; and iv. purifying the residue obtained at step iii) to afford the compound of formula II; wherein compound of formula A and compound of formula B in step i) are represented as; wherein

[0047] R is selected from (un) substituted alkyl, (un)substituted aryl, (un)substituted heteroaryl, (un)substituted alkoxy, halo, nitro, trifluoromethyl, (un)substituted alkynyl, (un)substituted alkylene, (un)substituted allyl, (un)substituted cyclic ring, cycloalkyl, heteroalkylene, arylalkyl, heterocycloalkyl, heteroaryk ilkylheteroaryl, haloalkyl, heteroalkyl, alkylamino, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, alkylsulfonylamino, aminosulfonyl, alkylaminosulfonyl, dialkylamino sulfonyl, aminosulfonylamino, aminocarbonylamino, alkylaminosulfonylamino, dialkylaminosulfonylamino, alkylaminocarbonylamino, alkylcarbamoyl, alkylthio, alkylsulfinyl, alkylsulfonyl, carbamyl, cyano-alkyl, alkoxyalkyl, dialkylamino, dialkylcarbamyl, haloalkoxy, haloalkyl, ester, ether, acetal, thioacetal, ketal, thioketal, carbamate, and carbonate; and

[0048] R13, R14, R15, R16, R17, R18and R19are selected from hydrogen, (un)substituted alkyl, (un)substituted aryl, (un)substituted heteroaryl, (un)substituted alkoxy, halo, nitro, trifluoromethyl, (un)substituted alkynyl, (un) substituted alkylene, (un)substituted allyl, (un)substituted cyclic ring, cycloalkyl, heteroalkylene, arylalkyl, heterocycloalkyl, heteroarylalkyl, alkylheteroaryl, haloalkyl, heteroalkyl, alkylamino, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, alkylsulfonylamino, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, aminosulfonylamino, aminocarbonylamino, alkylamino sulfonylamino, dialkylaminosulfonylamino, alkylaminocarbonylamino, alkylcarbamoyl, alkylthio, alkylsulfinyl, alkylsulfonyl, carbamyl, cyano-alkyl, alkoxyalkyl, dialkylamino, dialkylcarbamyl, haloalkoxy, haloalkyl, ester, ether, acetal, thioacetal, ketal, thioketal, carbamate, and carbonate; and

[0049] X is selected from OAc, Cl, Br, I, F, OTF.

[0050] In an embodiment, the solvent at step i) is selected from toluene, xylene, benzene, hexane, cumene, cyclohexane, ethyl acetate, butyl acetate, isopropyl acetate, and 1, 4-dioxane or any of mixtures thereof.

[0051] In an embodiment, the organic solvent at step ii) is selected from from ethyl acetate, propyl actetate, isopropyl cetate, butyl acetate, and isobutyl acetate or mixtures thereof.

[0052] In an embodiment, the base used in step i) is selected from alkali metal carbonate, alkali metal bicarbonate, alkali metal ter-butoxide, and alkali metal hydroxide.

[0053] In an embodiment, the base is selected from alkali metal ter-butoxide.

[0054] The process is represented below in scheme- 1

[0055]

[0056] In an aspct of an embodiment, the process for the preparation of compound of formula II by using catalyst of formula I has been optimized by conducting several experiments using different above-said bases, above-said solvent system, Ni cat of formula I with X= OAc, and halides and compound 3a as a representative compound of formula A and compound 4a as a representative compound of formula B. These experimental data indicate that the catalyst compound 2a as a representative compound of formula I provides 93% yield of the compound 5aa as a representative compound of formula II (as shown in scheme 2).

[0057] In an embodiment, the present invention provides a alkylated 2-pyridones synthesized in high yields, which are important chemical moiety as it is a part of many biologically important compounds and natural products, such as ciclopirox, milrinone, A58365A, and sophoramine.

[0058] EXAMPLES

[0059] All the chemicals used for the preparation of catalyst (I) and compounds II and III wre obtained form commercial sources, like SpectroChem, TCI and Merck Chemicals, India.

[0060] Representative procedure for the synthesis of Ligand and Ni-complexes of Formula I

[0061] Example 1: Representative procedure for the synthesis of compound la of formula 1: To a Schlenk tube, N -(2-fluorophenyl)quinolin-8-amine (0.1 g, 0.42 mmol) and KPPh2 (1.26 mL, 0.5 M in THF), was added under an tmosphere. The resulting reaction mixture was heated at 150 °C for 5 days. At a temperature in the range of 25-30°C, the reaction mixture was diluted with EtOAc (20 mL). After evaporation of solvents in vacuo, the crude product was purified by column chromatography on neutral alumina (petroleum ether / EtOAc: 100 / 1) to yield 1 (0.13 g, 77%) as a yellow solid.

[0062] Example 2: Representative procedure for the synthesis of compound 2a of Formula (I)

[0063] To an oven dried Schlenk flask was charged with (Compound la)-H (0.1 g, 0.742 mmol) and Ni(OAc)2 (0.15 g, 0.890 mmol) and THF (20 mL) was added into it. To the resultant reaction mixture, EtsN (0.09 g, 0.890 mmol) was added and the reaction mixture was stirred at 70 °C for 5 h in a preheated oil bath. The reaction mixture was cooled to 25-30°C and all the volatiles were evaporated. The product was then extracted with toluene (10 mL X 2), and then concentrated to 5 mL. Addition of hexane (10 mL) afforded a brown precipitate, which was filtered, washed with additional hexane and dried under vacuum. Yield: 0.33 g, 85%.

[0064]

[0065] Example 3: Representative Procedure for compound of formula II: 6-Octyl-2H-[l,2'- bipyridin] -2-one (5aa):

[0066] To a flame-dried screw-cap tube equipped with magnetic stir bar were introduced 2H -[1 ,2'- bipyridin] -2-one (3a; 0.034 g, 0.20 mmol), 1 -chlorooctane (4a; 0.059 g, 0.40 mmol), Cat.2a (0.010 g, 0.02 mmol, 10.0 mol%) and LiOtBu (0.032 g, 0.40 mmol) inside the glove box. To the above mixture in the tube was added toluene (0.5 mL). The resultant reaction mixture in the tube was immersed in a preheated oil bath at 120 °C and stirred for 24 h. At 25-30°C, the reaction mixture was quenched with distilled H2O (10.0 mL) and the crude product was extracted with EtOAc (15 mL x 3). The combined organic extract was dried over Na2SO4and the volatiles were evaporated in vacuo. The remaining residue was purified by column chromatography on neutral alumina (petroleum ether / EtOAc: 1 / 2) to yield 5aa (0.053 g, 93%) as a white solid. CH2), 27.9 (CH2), 22.7 (CH2), 14.2 (CH3). HRMS (ESI): m / z Calcd for CI8H24ON2+ H+[M + H]+285.1961; Found 285.1953.

[0067] Characterization data (Table 1) for all synthesized compounds of Formula II by using above representative procedure:

[0068] Table 1

[0069] ADVANTGAES OF THE INVENTION:

[0070] • Developed new, inexpensive and abundant nickel based catalyst, (QNNPph2)Ni(OAc).

[0071] • Method / process developed is new / • Used readily available and unactivated alkyl chloride as a coupling partner

[0072] • Challenging alkyl chlorides used as an alkylating precursors

Claims

We Claim:

1. A pincer ligated nickel based catalyst o a I, represented as:whereinR1and R2are selected from (un)substituted aryl, benzyl, alkyl, and cyclo-alkyl; optionally R1and R2together with P may form a 5-6 membered saturated or unsaturated cyclic ring;R3, R4, R5, R6, R7, R8, R9, R10, R11and R12are selected from hydrogen, (un)substituted alkyl, (un)substituted cyclo-alkyl, alkoxy, and (un)substituted aryl; andX is selected from chloro, bromo, iodo, OAc, and OTf.

2. The pincer ligated nickel based catalyst of formula I as claimed in claim 1, wherein the alkyl is selected from propyl, iso-propyl, butyl, and ter-butyl.

3. A process for the preparation of said pincer ligated nickel based catalyst of formula I as claimed in claim 1, comprising the steps of: a) mixing (un)substituted A-(2-fluoro-aryl)quinolinyl-amine compound of formula D and potassium salt of PR1R2under argon atmosphere and heating the reaction mixture at a temperature in the range of 140-160°C for a time period in the range of 5-6 days to obtain crude product, followed by diluting the crude product with a solvent, evaporating and purifiying to afford (QNNPR1R2)-H compound of formula 1 as a yellow solidCompound D Compound 1 ; and b) mixing the compound 1 obtained at sit ;h Ni(X)2, an organic base in a solvent and heating at a temperature in the range of 65-70°C for a time period in the range of 5-6 hr followed by extraction using extraction solvent, evaporation and separation of solid using precipitation inducing solvent, filtering, washing and drying to afford pincer ligated nickel based catalyst of formula I.

4. The process as claimed in claim 3, wherein the solvent used at step a) is selected from ethyl acetate, propyl actetate, isopropyl cetate, butyl acetate, isobutyl acetate, di-tert-butyl ether, di(propylene glycol) methyl ether, dibutyl ether, diethyl ether, diisopropyl ether, dimethoxyethane, dimethoxymethane, 1,4- dioxane, tetrahydrofuran, toluene, and xylene, or any of mixtures thereof; the solvent used in step b) is selected from tetrahydrofuran, toluene, xylene, benzene, hexane, cyclohexane, ethyl acetate, butyl acetate, and isopropyl acetate, or any of mixtures thereof; the extraction solvent is selected from ethyl acetate, propyl actetate, isopropyl cetate, butyl acetate, isobutyl acetate, di-tert-butyl ether, di(propylene glycol) methyl ether, dibutyl ether, diethyl ether, diisopropyl ether, dimethoxyethane, dimethoxymethane, 1,4- dioxane, tetrahydrofuran, toluene, and xylene, or any of mixtures thereof; and the precipitation inducing solvent is hexane.

5. The process as claimed in claim 3, wherein the organic base is selected from triethylamine (Et3N), DIPEA (N,N-diisopropylethylamine), DBU (1,8- Diazabicyclo[5.4.0]undec-7-ene), pyridine, and guanidine.

6. A process for the preparation of C-6 alkylated pyridones and compounds related thereof of formula II comprising reacting pyridinone and R-halide in presence of said nickel catalyst of formula I as claimed in claim 1, wherein the compound of formula II is represented by:whereinR is seleced from (un)substituted alkyl, (un)substituted aryl, (un)substituted heteroaryl, (un)substituted alkoxy, halo, nitro, trifluoromethyl, (un)substituted alkynyl, (un)substituted alkylene, (un)substituted allyl, (un)substituted cyclic ring, cycloalkyl, heteroalkylene, arylalkyl, heterocycloalkyl, heteroarylalkyl, alkylheteroaryl, haloalkyl, heteroalkyl, alkylamino, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, alkylsulfonylamino, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, amino sulfonylamino, aminocarbonylamino, alkylamino sulfonylamino, dialkylamino sulfonylamino, alkylaminocarbonylamino, alkylcarbamoyl, thio, alkylthio, alkylsulfinyl, alkylsulfonyl, carbamyl, cyano-alkyl, alkoxyalkyl, dialkylamino, dialkylcarbamyl, haloalkoxy, haloalkyl, ester, ether, acetal, thioacetal, ketal, thioketal, carbamyl, and carbonyl; andR13, R14, R15, R16, R17, R18and R19are selected from hydrogen, (un) substituted alkyl, (un)substituted aryl, (un)substituted heteroaryl, (un)substituted alkoxy, halo, nitro, trifluoromethyl, (un) substituted alkynyl, (un) substituted alkylene, (un) substituted allyl, (un)substituted cyclic ring, cycloalkyl, heteroalkylene, arylalkyl, heterocycloalkyl, heteroarylalkyl, alkylheteroaryl, haloalkyl, heteroalkyl, alkylamino, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, alkylsulfonylamino, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, amino sulfonylamino, aminocarbonylamino, alkylaminosulfonylamino, dialkylaminosulfonylamino, alkylaminocarbonylamino, alkylcarbamoyl, thio, alkylthio, alkylsulfinyl, alkylsulfonyl, carbamyl, cyano-alkyl, alkoxyalkyl, dialkylamino, dialkylcarbamyl, haloalkoxy, haloalkyl, ester, ether, acetal, thioacetal, ketal, thioketal, carbamayl, and carbonyl.

7. The process as claimed in claim 6, wherein the process comprises steps of:i. heating a reaction mixture containing a compound of formula A, a compound of formula B, the catalyst of formula base in a solvent at a temperature in the range of 120-140°C for a time period in the range of 23-25 hr; ii. quenching and extracting the reaction mixture obtained at step i) using an organic solvent to obtain organic extract; iii. drying and evaporating the organic extract obtained at step ii) under vacuum to obtain a residue; and iv. purifying the residue obtained at step iii) to afford the compound of formula II; wherein the compound of formula A and compound of formula B in step i) are represented by:whereinR is selected from (un)substituted alkyl, (un)substituted aryl, (un)substituted heteroaryl, (un)substituted alkoxy, halo, nitro, trifluoromethyl, (un)substituted alkynyl, (un)substituted alkylene, (un)substituted allyl, (un)substituted cyclic ring, cycloalkyl, heteroalkylene, arylalkyl, heterocycloalkyl, heteroarylalkyl, alkylheteroaryl, haloalkyl, heteroalkyl, alkylamino, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, alkylsulfonylamino, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, amino sulfonylamino, aminocarbonylamino, alkylaminosulfonylamino, dialkylamino sulfonylamino, alkylaminocarbonylamino, alkylcarbamoyl, alkylthio, alkylsulfinyl, alkylsulfonyl, carbamyl, cyano-alkyl, alkoxyalkyl, dialkylamino, dialkylcarbamyl, haloalkoxy, haloalkyl, ester, ether, acetal, thioacetal, ketal, thioketal, carbamate, and carbonate; andR13, R14, R15, R16, R17, R18and R19are selected from hydrogen, (un) substituted alkyl, (un)substituted aryl, (un)substituted heteroaryl, (un)substituted alkoxy, halo, nitro,trifluoromethyl, (un) substituted alkynyl, (un)substituted alkylene, (un) substituted allyl, (un)substituted cyclic ring, cycloall eroalkylene, arylalkyl, heterocycloalkyl, heteroarylalkyl, alkylheteroaryl, haloalkyl, heteroalkyl, alkylamino, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, alkylsulfonylamino, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, aminosulfonylamino, aminocarbonylamino, alkylaminosulfonylamino, dialkylaminosulfonylamino, alkylaminocarbonylamino, alkylcarbamoyl, alkylthio, alkylsulfinyl, alkylsulfonyl, carbamyl, cyano-alkyl, alkoxyalkyl, dialkylamino, dialkylcarbamyl, haloalkoxy, haloalkyl, ester, ether, acetal, thioacetal, ketal, thioketal, carbamate, and carbonate; and X is selected from OAc, Cl, Br, I, F, OTF.

8. The process as claimed in claim 7, wherein the solvent used in step i) is selected from toluene, xylene, benzene, hexane, cumene, cyclohexane, ethyl acetate, butyl acetate, isopropyl acetate, and 1, 4-dioxane or any of mixtures thereof.

9. The process as claimed in claim 7, wherein the organic solvent used in step ii) is selected from from ethyl acetate, propyl actetate, isopropyl cetate, butyl acetate, and isobutyl acetate or mixtures thereof.

10. The process as claimed in claim 7, wherein the base used in step i) is selected from alkali metal carbonate, alkali metal bicarbonate, alkali metal ter-butoxide, and alkali metal hydroxide.

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