Crystalline forms of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1h,2h,3h,4h,5h-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one and salts thereof, method of preparation, and uses thereof

Abstract

The present disclosure relates to hydrochloride salts of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2- dihydropyridin-2-one (Compound 1), a potent, and orally active selective melanin-concentrating hormone receptor 1 (MCHR1) antagonist useful in the treatment and / or prevention of obesity, obesity related comorbid conditions and complications, diabetes, metabolic disorders, coronary artery disease, cerebrovascular disease, peripheral artery disease, hypertension, endocrine disorders, psychiatric conditions, personality disorders, eating disorders, sleep-wake cycle disorders, substance abuse and addictive disorders, chronic liver and kidney diseases, gastrointestinal disorders, chronic conditions of the musculo- skeletal system, osteoporosis, cancer, and also in Prader-Willi Syndrome (PWS) or in one or more symptoms of PWS. The present disclosure also relates to crystalline forms of 4-[(5- chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one in free base form, different crystalline forms of the hydrochloride salt thereof, methods of producing the same, pharmaceutical compositions thereof, and therapeutic applications thereof as well.

Description

[0001]Crystalline forms of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one and salts thereof, method of preparation, and uses thereof Field of invention The present disclosure relates to hydrochloride salts of 4-[(5-chloropyridin-2- yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2- dihydropyridin-2-one (Compound 1), a potent, and orally active selective melanin- concentrating hormone receptor 1 (MCHR1) antagonist useful in the treatment and / or prevention of obesity, obesity related comorbid conditions and complications, diabetes, metabolic disorders, coronary artery disease, cerebrovascular disease, peripheral artery disease, hypertension, endocrine disorders, psychiatric conditions, personality disorders, eating disorders, sleep-wake cycle disorders, substance abuse and addictive disorders, chronic liver and kidney diseases, gastrointestinal disorders, chronic conditions of the musculo- skeletal system, osteoporosis, cancer, and also in Prader-Willi Syndrome (PWS) or in one or more symptoms of PWS. The present disclosure also relates to crystalline forms of 4-[(5- chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7- a]indol-9-yl]-1,2-dihydropyridin-2-one in free base form, different crystalline forms of the hydrochloride salt thereof, methods of producing the same, pharmaceutical compositions thereof, and therapeutic applications thereof as well. Background of the invention MCHR1 antagonists, including 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2- yl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one in free base form (depicted below, referred as Compound 1 hereinafter), and its maleic acid salt, is reported in WO 2016 / 166684 A1. Compound 1 The melanin-concentrating hormone (MCH) plays a multifaceted role in energy homeostasis and being central to the control of hypothalamic food intake and energy expenditure (Pissios et al., Endocr Rev 2006, 27(6):606-620). MCH has attracted considerable attention because of its effects on food intake and body weight and its receptor MCHR1 is still one of the viable targets for obesity therapy (Pissios P., Peptides 2009, 30(11):2040- 2044). MCH is one of the most potent central stimulators of feeding, regulates energy balance and mood (Pissios et al., Endocrinology 2003, 144(8):3514-3523; Pissios et al., Endocr Rev 2006, 27(6):606-620; Forray C., Curr Opin Pharmacol 2003, 3: 85-89; Qu et al., Nature 1996, 380: 243-47; Hervieu G., Expert Opin Ther Targets 2003, 7: 495-511; Chung et al., J Mol Neurosci 2011, 43:115-21). Prader-Willi syndrome (PWS) is a rare complex neurodevelopmental genetic disorder - resulting from absence of expression of imprinted genes in the paternally derived region of the chromosome 15q11.2-q13. PWS is the most common syndromic cause of life-threatening obesity with an estimated incidence of 1 / 10000 to 1 / 25000 live births, occurring equally in both males and females, and across all ethnicities. The syndromic obesity driven by profound hyperphagia arise from neurodevelopmental consequences of the deletion of the small nucleolar C / D box RNA 116 (SNORD116) cluster that always involved in paternal copy deletion cases as it is proved to be the minimal deletion region (Holm et al., Pediatrics 1993, 91:398-402; Gunay-Aygun et al., Pediatrics 2001, 108:E95; Duker et al., Eur. J. Hum. Genet.2010; 18: 1196-201; de Smith et al., Hum. Mol. Genet.2009, 18:3257-65; Bieth et al., Eur. J. Human Genet.2015, 23:252-255; Polex-Wolf et al., J. Clin. Invest.2018, 128:960–969; Tan et al., Genes 2020, 11:128; Chung et al., Open Biology 2020, 10:200195). Hyperphagia, the key behavioral symptom in PWS has remarkable impact on patient and caregiver well-being that extends far beyond the effect of weight gain alone. Management of hyperphagia is ranked as the highest priority among priorities for PWS treatment goals among caregivers. Uncontrollable appetite, weight gain and impaired reproduction in PWS may be explained by overactive MCH neurons as the “checks and balances” lost because of the reduced ORX population in the lateral hypothalamus. Prevention of the MCH overactivation most likely improves the MCH-ORX balance that may ultimately help patients in reducing the feeding-related symptoms. According to the latest preclinical reports the MCH-MCHR1 system is overactivated due to the impaired ORX control, PWS patients could benefit from MCHR1 antagonist treatment to gain control over hyperphagia and obesity (Pace M., JCI Insight 2020, 5:e137495; Pace et al., Hum. Mol. Genet. 2020, 29:2051-2064; Linehan et al., Mol. Meatabolism 2020, 36:100977; Linehan et al., J. Physiol 2022, 596:305-316). MCHR1 antagonists thus can be useful in the treatment of a disease or condition associated with melanin concentrating hormone receptor 1 activity, such as obesity, obesity related comorbid conditions and complications, diabetes, metabolic disorders, coronary artery disease, cerebrovascular disease, peripheral artery disease, hypertension, endocrine disorders, psychiatric conditions, personality disorders, eating disorders, sleep- wake cycle disorders, substance abuse and addictive disorders, chronic liver and kidney diseases, gastrointestinal disorders, chronic conditions of the musculo-skeletal system, osteoporosis, cancer, and also in PWS or in one or more symptoms of PWS. For pharmaceutical formulation and patient administration purposes, there is a need to provide Compound 1 in a suitable form. However, solid forms of Compound 1 and its pharmaceutically acceptable salts, such as crystalline forms, co-crystals or pseudo- polymorphs / solvatomorphs are not characterized in the prior art. Polymorphism is the ability of a compound to exist in two or more different crystalline phases that differ in the arrangement of the molecules in crystal lattice (J. Bernstein (2002) Polymorphism in molecular Crystals, Oxford Univ. Press. p.2-4). Although polymorphs have the same chemical composition, they differ in packing and geometrical arrangement and exhibit different physical properties such as melting point, X-ray diffraction patterns, crystal habit, density, stability, solubility rate, mechanical properties (such as hardness, compactibility, tabletting properties, flow, blending), rheological parameters, etc. Extensive studies are carried out in the pharmaceutical industry for the development of different polymorphs of various drug substances (R. Hilfiker (ed.2006) Polymorphism in the Pharmaceutical Industry, Wiley-VCH, p.1-15), to obtain suitable polymorphs or pseudo- polymorphs that possess improved performance characteristics. A general requirement for active ingredients in the development of a pharmaceutical composition is that the active ingredient has the appropriate physical, physico-chemical and chemical parameters. Examples of such parameters include solubility, in particular water solubility. Another important feature that should be taken into account in industrial-scale production is the easy handling and the good isolability, which is extremely important for the economicalness of the manufacturing process. A further important aspect is that the solid form of the active ingredient has appropriate physical and chemical stability, for example, not hygroscopic, and does not degrade significantly. Furthermore, different polymorphic forms of a given salt may have different solid phase characteristics, physical and chemical stability. To date, there is no reliable method by which the true number of different solid forms in which a given compound can physically exist can be clearly predicted for a given new chemical entity. This also holds for predicting all complex physical and chemical properties that needs to be considered when pharmaceutical development of a given form is concerned. Therefore, exploring the polymorphic landscape of a compound and finding as well as making the truly existing solid forms remains an experimental challenge, and important field of invention in the pharmaceutical field. Seeking to find new solid forms of a compound with advantageous pharmaceutical properties is highly desirable. Pseudo-polymorphism is the ability of a compound to coexist with different solvents in two or more different crystalline phases. It is generally advisable not to use solvents that can form solvates with a particular compound in a crystallization process to produce that compound (Hilfiker et al (2019), Polymorphism in the Pharmaceutical Industry: Solid Form and Drug Development; p.245-246; Wiley-VCH). Moreover, it is highly disadvantageous to use solvated forms, apart from hydrates for pharmaceutical development as traces of an organic solvent may be harmful (Bhatia et al (2018), Dosage form design parameters, Chapter 2.2.2.: Crystal solvates and hydrates, Elsevier). Also, solvate forms are known to show variable compositions potentially raising reproducibility and long-term stability issues. The international patent application WO 2016 / 166684 provides a preparation method for Compound 1 maleate salt. Reproduction experiments of WO 2016 / 166684 Example 20(b) proved that the isolated crystalline solid is an ethanol solvate, which is not suitable for pharmaceutical development. Further experiments proved that the maleate salt of Compound 1 shows increased tendency to form solvated forms revealing a variety of pseudo-polymorphs in different organic solvents like methanol, ethanol, dichloromethane, dimethyl sulfoxide etc.. A common characteristic of these solvated forms is increased solvent content (above 1% by thermogravimetric analysis (TGA)). The increased tendency to form new polymorphs, especially solvates represents a risk of polymorph transformation or change in composition during storage or pharmaceutical formulation. As a consequence, the use of the maleate salt of Compound 1 in pharmaceutical product is disadvantageous. Therefore, it is desirable to provide improved forms of Compound 1 that are suitable for pharmaceutical formulation and for administration to humans. The international patent application WO 2016 / 166684 also provides an isolation for Compound 1 as free base. Reproduction experiments proved that the product of Example 20(a) in WO 2016 / 166684 is a crystalline form with unfavourable stability properties, i.e. it is a metastable crystalline form (Form B) of the base which is not suitable for pharmaceutical development. Form B of Compound 1 tends to undergo polymorph transformation in contact with most solvents as well as when exposed to heating. Thus, use of Compound 1 Form B in pharmaceutical product is disadvantageous and does not fulfil the need for a suitable solid form of Compound 1 for pharmaceutical formulation and for the treatments that effectively inhibit MCHR1 and are tolerable to the patients. Apart from the disadvantageous maleate and base form no other solid forms of Compound 1 were ever described in the prior art. Accordingly, it is desirable to find a new solid form of Compound 1 or its pharmaceutically acceptable salts that is suitable for pharmaceutical development and for administration to a patient in need of a treatment of a disease or condition associated with melanin concentrating hormone receptor 1 activity and is tolerable to such patient. Summary of the invention The present disclosure relates to hydrochloride salts of 4-[(5-chloropyridin-2- yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2- dihydropyridin-2-one (Compound 1), a potent, and orally active selective melanin- concentrating hormone receptor 1 (MCHR1) antagonist useful in the treatment and / or prevention of obesity, obesity related comorbid conditions and complications, diabetes, metabolic disorders, coronary artery disease, cerebrovascular disease, peripheral artery disease, hypertension, endocrine disorders, psychiatric conditions, personality disorders, eating disorders, sleep-wake cycle disorders, substance abuse and addictive disorders, chronic liver and kidney diseases, gastrointestinal disorders, chronic conditions of the musculo- skeletal system, osteoporosis, cancer, and also in Prader-Willi Syndrome (PWS) or in one or more symptoms of PWS. The present disclosure also relates to the stable crystalline forms of Compound 1 in free base form, to the stable crystalline form of the hydrochloride salt thereof, methods of producing the same solid forms, pharmaceutical compositions thereof, and therapeutic applications thereof as well. Brief description of the drawings Figure 1 illustrates the X-ray diffraction pattern of Compound 1 maleate salt obtained in Reference example 1. Figure 2 illustrates the X-ray diffraction pattern of Compound 1 maleate salt obtained in Reference example 2. Figure 3 illustrates the X-ray diffraction pattern of Compound 1 maleate salt obtained in Reference example 3. Figure 4 illustrates the X-ray diffraction pattern of Compound 1 maleate salt obtained in Reference example 4. Figure 5 illustrates the X-ray diffraction pattern of Compound 1 maleate salt obtained in Reference example 5. Figure 6 illustrates the X-ray diffraction pattern of Compound 1 maleate salt obtained in Reference example 6. Figure 7 illustrates the X-ray diffraction pattern of Compound 1 maleate salt obtained in Reference example 7. Figure 8 illustrates the X-ray diffraction pattern of Compound 1 maleate salt obtained in Reference example 8. Figure 9 illustrates the X-ray diffraction pattern of Compound 1 maleate salt obtained in Reference example 9. Figure 10 illustrates the TGA thermogram of Compound 1 maleate salt obtained in Reference example 1. Figure 11 illustrates the TGA thermogram of Compound 1 maleate salt obtained in Reference example 2. Figure 12 illustrates the TGA thermogram of Compound 1 maleate salt obtained in Reference example 3. Figure 13 illustrates the TGA thermogram of Compound 1 maleate salt obtained in Reference example 4. Figure 14 illustrates the TGA thermogram of Compound 1 maleate obtained in Reference example 5. Figure 15 illustrates the TGA thermogram of Compound 1 maleate salt obtained in Reference example 6. Figure 16 illustrates the TGA thermogram of Compound 1 maleate salt obtained in Reference example 7. Figure 17 illustrates the TGA thermogram of Compound 1 maleate salt obtained in Reference example 8. Figure 18 illustrates the X-ray diffraction pattern of Compound 1 hydrochloride salt Form A. Figure 19 illustrates the infrared spectrum of Compound 1 hydrochloride salt Form A. Figure 20 illustrates the Raman spectrum of Compound 1 hydrochloride salt Form A. Figure 21 illustrates the DSC trace of Compound 1 hydrochloride salt Form A. Figure 22 illustrates the TGA thermogram of Compound 1 hydrochloride salt Form A. Figure 23 illustrates the X-ray diffraction pattern of Compound 1 free base Form A. Figure 24 illustrates the infrared spectrum of Compound 1 free base Form A. Figure 25 illustrates the Raman spectrum of Compound 1 free base Form A. Figure 26 illustrates the DSC trace of Compound 1 free base Form A. Figure 27 illustrates the TGA thermogram of Compound 1 free base Form A. Figure 28 illustrates the X-ray diffraction pattern of Compound 1 free base Form B. Figure 29 illustrates the infrared spectrum of Compound 1 free base Form B. Figure 30 illustrates the Raman spectrum of Compound 1 free base Form B. Figure 31 illustrates the DSC trace of Compound 1 free base Form B. Figure 32 illustrates the X-ray diffraction pattern of Compound 1 free base Form C. Figure 33 illustrates the DSC trace of Compound 1 free base Form C. Figure 34 illustrates the TGA thermogram of Compound 1 free base Form C. Figure 35 illustrates the X-ray diffraction pattern of Compound 1 free base Form D. Figure 36 illustrates the infrared spectrum of Compound 1 free base Form D. Figure 37 illustrates the Raman spectrum of Compound 1 free base Form D. Figure 38 illustrates the DSC trace of Compound 1 free base Form D. Figure 39 illustrates the TGA thermogram of Compound 1 free base Form D. Figure 40 illustrates the X-ray diffraction pattern of Compound 1 free base obtained in Reference example 10. Figure 41 illustrates the X-ray diffraction pattern of Compound 1 free base obtained in Example 3. Detailed description of the invention As summarized above Compound 1 maleate was found disadvantageous for pharmaceutical formulation and for the treatments that effectively inhibit MCHR1 and are tolerable to the patients. The international patent application WO 2016 / 166684 provides a preparation method for Compound 1 maleate salt (Reference example 1). The sample was found to be crystalline by XRPD (Figure 1) but a significant weight loss of 3.9% was detected by TGA. Reproduction experiment of WO 2016 / 166684 Example 20(b) – Reference example 2 - proved that the isolated crystalline solid is an ethanol solvate (TGA: 5.1%). It is highly disadvantageous to use solvated forms, apart from hydrates for pharmaceutical development as traces of an organic solvent may be harmful (Bhatia et al (2018), Dosage form design parameters, Chapter 2.2.2.: Crystal solvates and hydrates, Elsevier). Also, solvate forms are known to show variable compositions potentially raising reproducibility and long-term stability issues. As a consequence solvates in general are not suitable for pharmaceutical development, and also It is generally advisable not to use solvents that can form solvates with a particular compound in a crystallization process to produce that compound (Hilfiker et al (2019), Polymorphism in the Pharmaceutical Industry: Solid Form and Drug Development; p.245-246; Wiley-VCH). Further experiments were carried out to find a suitable polymorph of Compound 1 maleate for pharmaceutical development. Recrystallization experiments from various solvents (e.g. methanol, ethanol, dichloromethane, dimethyl sulfoxide) and by various crystallization methods (e.g. suspension stirring, cooling, evaporation) were designed and carried out to identify a stable and solvent-free polymorph of Compound 1 maleate (Reference example 2-9). In these experiments several crystalline forms were identified (Figures 1-9) but the residual solvent content (determined by TGA) was above acceptance limit in all these experiments indicating them to be solvates (Figures 10-17). The high number of new pseudo- polymorphs combined with the high residual solvent content (above 1% by TGA) represent a risk of polymorph transformation or change in composition during storage or pharmaceutical formulation. As a consequence, the use of the maleate salt of Compound 1 in pharmaceutical product is disadvantageous and a need for a different, more stable solid form arose. As summarized above the present invention relates to stable crystalline free base and crystalline hydrochloride salt of Compound 1 that are acceptable for pharmaceutical development. This description also relates to the identification and process for the preparation of said crystalline forms. Crystalline solid phases can be identified by X-ray diffraction: the powder X-ray diffraction pattern or the position of one or more diffraction peaks are characteristics of the crystalline material. Alternatively, vibrational spectroscopy, such as IR and Raman spectroscopy are also suitable and widely used methods for distinguishing the different polymorphic / pseudo-polymorphic / amorphous forms. Although vibrational spectroscopy primarily probe local, short-range order (intramolecular vibrations), the vibrational frequencies are also influenced by their surrounding environment, making these frequencies not only to conformational polymorphism but also to the way the molecules are packed. Consequently, different polymorphs typically have different vibrational spectra, provided they are measured with sufficiently high wavenumber resolution (Hilfiker et al (2019), p. 418). Therefore, each crystalline forms of Compound 1 free base and hydrochloride salt of the present invention can be identified and distinguished from other crystalline forms either by one or more of the following solid state analytical characteristics: characteristic XRPD diffraction peaks, IR absorption bands or Raman peaks. One aspect of the present invention is the hydrochloride salt of Compound 1. The salt can exist in a variety of forms such as oil or solid. The solid can be amorphous, crystalline or a mixture of both. In another aspect the present invention provides a process for the preparation of Compound 1 hydrochloride salt comprising: a) providing a solution of Compound 1 in any suitable solvent; b) mixing the solution is step a) with a hydrochloric acid solution c) agitating the slurry; and d) isolating Compound 1 hydrochloride salt. The solvent employed in step a) is selected from the group consisting of water, methanol, ethanol, isopropanol, 2-propanol, 1-butanol, t-butyl alcohol, 1-pentanol, 2- pentanol, acetone, butanone, 2-pentanone, 3-pentanone, methyl butyl ketone, methyl ethyl ketone, methyl isobutyl ketone, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, t- butyl acetate, isobutyl acetate, methylene dichloride, ethylene dichloride, acetonitrile, tetrahydrofuran, 1,4-dioxane, 2-methoxyethanol, diethyl ether, diisopropyl ether, methyl t- butyl ether or mixtures thereof. The solvent employed in step b) is selected from the group consisting of water, methanol, ethanol, isopropanol, 2-propanol, 1-butanol, t-butyl alcohol, 1-pentanol, 2- pentanol, acetone, butanone, 2-pentanone, 3-pentanone, methyl butyl ketone, methyl ethyl ketone, methyl isobutyl ketone, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, t- butyl acetate, isobutyl acetate, methylene dichloride, ethylene dichloride, acetonitrile, tetrahydrofuran, 1,4-dioxane, 2-methoxyethanol, diethyl ether, diisopropyl ether, methyl t- butyl ether or mixtures thereof. Step c) involves agitating the slurry by means of any suitable technique including stirrer bar, stir rod or shaker at any suitable temperature including reflux, room temperature, 0-5 °C or any other suitable temperature. Isolation of the product may be carried out under ambient conditions or in inert atmosphere (e.g. nitrogen). The product is a white or off white solid. Another aspect of the present invention is the stable anhydrate form of the hydrochloride salt of Compound 1, Form A. A further aspect of the present invention is the hydrochloride salt of Compound 1, comprising at least 5%, at least 10%, at least 20%, at least 40%, at least 60%, at least 80%, at least 90%, at least 95%, at least 99% of Compound 1 hydrochloride salt Form A. The X-ray diffraction pattern of Compound 1 hydrochloride salt Form A is shown on Figure 18. Detailed peak list is shown in Table 1. Most characteristic peaks of Compound 1 hydrochloride salt Form A are at 9.2, 12.5, 14.5, 15.1, 15.8, 17.4±0.2° 2θ. Table 1 X-ray diffraction peaks of Compound 1 hydrochloride salt Form A. Compound 1 hydrochloride salt Form A can also be characterized by its FT-IR spectrum. The infrared spectrum of Compound 1 hydrochloride salt Form A is shown on Figure 19. Detailed list of absorption bands of Compound 1 hydrochloride salt Form A is shown in Table 2. The most characteristic absorption bands of Compound 1 hydrochloride salt Form A are at 2474, 2524, 1668, 1479 and 1222±4 cm−1. Table 2. Infrared absorption bands of Compound 1 hydrochloride salt Form A Compound 1 hydrochloride salt Form A can also be characterized by its Raman spectrum. The Raman spectrum of Compound 1 hydrochloride salt Form A is shown on Figure 20. Detailed list of Raman peaks of Compound 1 hydrochloride salt Form A is shown in Table 3. Most characteristic Raman peaks of Compound 1 hydrochloride salt Form A are at 1549, 1344, 1303, 1257 and 747 cm−1. Table 3. Raman peaks of Compound 1 hydrochloride salt Form A Compound 1 hydrochloride salt Form A can also be characterized by its differential scanninc calorimetry (DSC) thermogram. A typical DSC thermogram of Compound 1 hydrochloride salt Form A is shown on Figure 21. Compound 1 hydrochloride salt Form A melts during decomposition with a broad endothermic DSC peak with a peak maximum between 250 and 300 °C. Compound 1 hydrochloride salt Form A is a true anhydrate form proven by its thermogravimetric (TGA) thermogram as shown on Figure 22. The weight loss of Compound 1 hydrochloride salt Form A is less than 1.0% (up to 175 °C). Chemical stability of Compound 1 hydrochloride salt Form A was assessed via a set of forced stability studies, as shown in Table 4. A sample of Compound 1 hydrochloride salt Form A was stored under different controlled conditions (50 °C dry, 75 °C dry and 50 °C 85% RH) for 10 days and analysed with the same methods as the initial sample. Table 4. Forced stability results of Compound 1 hydrochloride salt Form A at different conditions The impurity profile, loss on drying and polymorph form of the sample of Compound 1 hydrochloride salt Form A did not change during forced stability study, proving that Compound 1 hydrochloride salt Form A is stable at 50 °C, 75 °C and at 50 °C 85% RH for 10 days. The term solubility is used to measure the amount of Compound 1 hydrochloride salt (in μmol) that can be dissolved in 1 L of the simulated solvent. Simulated solvents include FaSSiF (fasted state simulated intestinal fluid) and FeSSiF (fed state simulated intestinal fluid). A drug substance is considered highly soluble according to biopharmaceutics classification system (BCS) when the highest strength is soluble in 250 mL or less of aqueous media within the pH range of 1 - 6.8 at 37 ± 1°C (Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System, Guidance for Industry, December 2017, https: / / www.gmp-compliance.org). Solubility data of Compound 1 HCl Form A in FaSSiF and FeSSiF solutions are shown in Table 5. In simulated fluids (FaSSiF and FeSSiF) Compound 1 HCl Form A is highly soluble up to 20 mg strength. Table 5 Solubility of Compound 1 HCl Form A. Analytical and physical characterization described above prove that Compound 1 hydrochloride salt Form A is a stable anhydrate polymorph of Compound 1 hydrochloride salt which is highly soluble in simulated media. It is not hygroscopic under normal conditions (up to 70% RH) but some precautions are required at high humidity. Analytical results indicate that said solid form is suitable for pharmaceutical development. In another aspect the present invention provides a process for the preparation of Compound 1 hydrochloride salt salt Form A comprising: a) providing a solution of Compound 1 hydrochloride salt salt in any suitable solvent; b) evaporating part of the solvent to obtain a suspension; and c) agitating the slurry; and d) isolating Compound 1 hydrochloride salt salt Form A. The solution provided in step a) may be provided by dissolving Compound 1 hydrochloride salt or by mixing Compound 1 with an appropriate amount of hydrochloric acid in solution. The solvent employed in step a) is selected from the group consisting of water, methanol, ethanol, isopropanol, 2-propanol, 1-butanol, t-butyl alcohol, 1-pentanol, 2- pentanol, acetone, butanone, 2-pentanone, 3-pentanone, methyl butyl ketone, methyl ethyl ketone, methyl isobutyl ketone, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, t- butyl acetate, isobutyl acetate, methylene dichloride, ethylene dichloride, acetonitrile, tetrahydrofuran, 1,4-dioxane, 2-methoxyethanol, diethyl ether, diisopropyl ether, methyl t- butyl ether or mixtures thereof. Step b) involves the evaporation of solvent by means of any suitable technique including rotational distillation device such as a rotary evaporator, open reactor or any other suitable technique. Evaporation may be induced by the elevation of temperature or by reduced pressure or a combination thereof. Step c) involves agitating the slurry by means of any suitable technique including stirrer bar, stir rod or shaker at any suitable temperature including reflux, room temperature, 0-5 °C or any other suitable temperature. Isolation of the product may be carried out under ambient conditions or in inert atmosphere (e.g. nitrogen). The product is a white or off white solid. In another aspect the present invention provides a process for the preparation of Compound 1 hydrochloride salt Form A comprising: a) providing a solution of Compound 1 hydrochloride salt in any suitable solvent; b) cooling the solution to obtain a slurry; and c) agitating the slurry; and d) isolating Compound 1 hydrochloride salt Form A. The solution provided in step a) may be provided by dissolving Compound 1 hydrochloride salt or by mixing Compound 1 with appropriate amount of hydrochloric acid in solution. The solvent employed in step a) is selected from the group consisting of water, methanol, ethanol, isopropanol, 2-propanol, 1-butanol, t-butyl alcohol, 1-pentanol, 2- pentanol, acetone, butanone, 2-pentanone, 3-pentanone, methyl butyl ketone, methyl ethyl ketone, methyl isobutyl ketone, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, t- butyl acetate, isobutyl acetate, methylene dichloride, ethylene dichloride, acetonitrile, tetrahydrofuran, 1,4-dioxane, 2-methoxyethanol, diethyl ether, diisopropyl ether, methyl t- butyl ether or mixtures thereof. The temperature of the solution may be any suitable temperature e.g. reflux temperature of the solvent, 50 °C, 40 °C, room temperature etc. Step b) involves the cooling of the solution to a lower temperature than in step a), e.g. to room temperature or 0-5 °C or any suitable temperature. Step c) involves agitating the slurry by means of any suitable technique including stirrer bar, stir rod or shaker at or below the temperature set at step b). Isolation of the product may be carried out under ambient conditions or in inert atmosphere (e.g. nitrogen). The product is a white or off white solid. In another aspect the present invention provides a process for the preparation of Compound 1 hydrochloride salt Form A comprising: a) providing a solution of Compound 1 hydrochloride salt in any suitable solvent; b) mixing the solution with an antisolvent to obtain a slurry; and c) agitating the slurry; and d) isolating Compound 1 hydrochloride salt Form A. The solvent employed in step a) and the antisolvent in step b) is selected from the group consisting of water, methanol, ethanol, isopropanol, 2-propanol, 1-butanol, t-butyl alcohol, 1-pentanol, 2-pentanol, acetone, butanone, 2-pentanone, 3-pentanone, methyl butyl ketone, methyl ethyl ketone, methyl isobutyl ketone, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, t-butyl acetate, isobutyl acetate, methylene dichloride, ethylene dichloride, acetonitrile, tetrahydrofuran, 1,4-dioxane, 2-methoxyethanol, diethyl ether, diisopropyl ether, methyl t-butyl ether or mixtures thereof. The temperature of the solution may be any suitable temperature e.g. reflux temperature of the solvent, 50 °C, 40 °C, room temperature etc. Mixing the solution in step b) might be carried out by dosing the solution to the antisolvent or by dosing the antisolvent to the solution. Dosing may be uncontrolled or controlled by means of any suitable technique. Step c) involves agitating the slurry by means of any suitable technique including stirrer bar, stir rod or shaker at or below the temperature set at step b). Isolation of the product may be carried out under ambient conditions or in inert atmosphere (e.g. nitrogen). The product is a white or off white solid. The international patent application WO 2016 / 166684 also provides an isolation for Compound 1 as free base. Reference example 10 proved that evaporation of the eluent as described in Example 20(a) in WO 2016 / 166684 produces a crystalline form of Compound 1 free base, Form B. Analytical characterization, especially DSC analysis, of Compound 1 Form B revealed that this form undergoes polymorph transformation at higher temperature and new form with melting point between 200 and 210 °C forms. These DSC results indicate that Compound 1 free base Form B may not the stable polymorph for Compound 1 free base. According to Ostwald's rule of stages (Ostwald, 1897) states that in a crystallisation, the system moves to equilibrium from an initial high-energy state through minimal changes in free energy, and thus implies that the least stable polymorph should be the first isolated in any crystallisation (Jonathan C. Burley, Melinda J. Duer, Robin S. Stein, Ranko M. Vrcelj, European Journal of Pharmaceutical Sciences, Volume 31, Issue 5, August 2007, Pages 271- 276). In order to obtain more stable polymorhps further crystallization experiments (e.g. Example 3) were designed and carried out using more controlled crystallization process: instead of fast evaporation of the eluent an additional re-suspension step was applied. In Example 3 a new polymorph of Compound 1 free base, Form A, was obtained with some traces of Form B. In further crystallization experiments pure Form A was prepared and characterized. Another aspect of the present invention is the stable anhydrate form of Compound 1 free base, Form A. A further aspect of the present invention is the crystalline solid form of Compound 1 free base, comprising at least 5%, at least 10%, at least 20%, at least 40%, at least 60%, at least 80%, at least 90%, at least 95%, at least 99% of Compound 1 free base Form A. The X-ray diffraction pattern of Compound 1 free base Form A is shown on Figure 23. Detailed peak list is shown in Table 6. Most characteristic peaks of Compound 1 free base Form A are at 5.9, 17.7, 18.1, 19.8 and 22.2° 2θ. Table 6 X-ray diffraction peaks of Compound 1 free base Form A Compound 1 free base Form A can also be characterized by its FT-IR spectrum. The infrared spectrum of Compound 1 free base Form A is shown on Figure 24. Detailed list of absorption bands of Compound 1 free base Form A is shown in Table 7. Most characteristic absorption bands of Compound 1 free base Form A are at 1663, 1478, 1220, 860, 795 and 766±4 cm−1. Table 7. Infrared absorption bands of Compound 1 free base Form A Compound 1 free base Form A can also be characterized by its Raman spectrum. The Raman spectrum of Compound 1 free base Form A is shown on Figure 25. Detailed list of Raman peaks of Compound 1 free base Form A is shown in Table 8. Most characteristic Raman peaks of Compound 1 free base Form A are at 1554, 1345, 1267, 1260 and 750±4 cm−1. Table 8. Raman peaks of Compound 1 Form A Compound 1 free base Form A can also be characterized by its DSC thermogram. A typical DSC thermogram of Compound 1 free base Form A is shown on Figure 26. Compound 1 free base Form A exhibits a single melting endothermal with onset temperature values between 200 and 210 °C. Compound 1 free base Form A is a true anhydrate form proven by its TGA thermogram as shown on Figure 27. The weight loss of Compound 1 free base Form A is less than 0.5% (up to 215 °C). Chemical stability of Compound 1 free base Form A was assessed via a set of forced stability studies, as shown in Table 9. A sample of Compound 1 free base Form A was stored under different controlled conditions (50 °C dry, 75 °C dry and 50 °C 85% RH) for 10 days and analysed with the same methods as the initial sample. Table 9. Forced stability results of Compound 1 free base Form A at different conditions The impurity profile, loss on drying and polymorph form of the sample of Compound 1 free base Form A did not change during forced stability study, proving that Compound 1 free base Form A is stable at 50 °C, 75 °C and at 50 °C 85% RH for 10 days. Solubility of Compound 1 free base Form A in PBS, FaSSiF and FeSSiF solutions are shown in Table 10. Compound 1 Form A is highly soluble up to 9 mg strength but in more acidic media solubility is even higher. Table 10. Solubility of Compound 1 Form A. Analytical and physical characterization described above proves that Compound 1 free base Form A is a stable non-hygroscopic anhydrate polymorph of Compound 1 free base which shows acceptable solubility in simulated media. Analytical results indicate that said solid form is suitable for pharmaceutical development. In another aspect the present invention provides a process for the preparation of Compound 1 free base Form A comprising: a) providing a solution of Compound 1 free base in any suitable solvent; b) evaporating part of the solvent to obtain a suspension; and c) agitating the slurry; and d) isolating Compound 1 free base Form A. The solvent employed in step a) is selected from the group consisting of water, methanol, ethanol, isopropanol, 2-propanol, 1-butanol, t-butyl alcohol, 1-pentanol, 2- pentanol, acetone, butanone, 2-pentanone, 3-pentanone, methyl butyl ketone, methyl ethyl ketone, methyl isobutyl ketone, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, t- butyl acetate, isobutyl acetate, methylene dichloride, ethylene dichloride, acetonitrile, tetrahydrofuran, 1,4-dioxane, 2-methoxyethanol, diethyl ether, diisopropyl ether, methyl t- butyl ether or mixtures thereof. Step b) involves the evaporation of solvent by means of any suitable technique including rotational distillation device such as a rotary evaporator, open reactor or any other suitable technique. Evaporation may be induced by the elevation of temperature or by reduced pressure or combination thereof. Step c) involves agitating the slurry by means of any suitable technique including stirrer bar, stir rod or shaker at any suitable temperature including reflux, room temperature, 0-5 °C or any other suitable temperature. Isolation of the product may be carried out under ambient conditions or in inert atmosphere (e.g. nitrogen). The product is a white or off white solid. In another aspect the present invention provides a process for the preparation of Compound 1 free base Form A comprising: a) providing a solution of Compound 1 free base in any suitable solvent; b) cooling the solution to obtain a slurry; and c) agitating the slurry; and d) isolating Compound 1 free base Form A. The solvent employed in step a) is selected from the group consisting of water, methanol, ethanol, isopropanol, 2-propanol, 1-butanol, t-butyl alcohol, 1-pentanol, 2- pentanol, acetone, butanone, 2-pentanone, 3-pentanone, methyl butyl ketone, methyl ethyl ketone, methyl isobutyl ketone, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, t- butyl acetate, isobutyl acetate, methylene dichloride, ethylene dichloride, acetonitrile, tetrahydrofuran, 1,4-dioxane, 2-methoxyethanol, diethyl ether, diisopropyl ether, methyl t- butyl ether or mixtures thereof. The temperature of the solution may be any suitable temperature e.g. reflux temperature of the solvent, 50 °C, 40 °C, room temperature etc. Step b) involves the cooling of the solution to a lower temperature than in step a), e.g. to room temperature or 0-5 °C or any suitable temperature. Step c) involves agitating the slurry by means of any suitable technique including stirrer bar, stir rod or shaker at or below the temperature set at step b). Isolation of the product may be carried out under ambient conditions or in inert atmosphere (e.g. nitrogen). The product is a white or off white solid. In another aspect the present invention provides a process for the preparation of Compound 1 free base Form A comprising: a) providing a suspension of a solid form of Compound 1 free base in any suitable solvent; b) agitating the slurry; and c) isolating Compound 1 Form A. In step a) the solid form of Compound 1 free base may be Form B or Form D or Form A or any mixture thereof. The solvent employed in step a) is selected from the group consisting of water, methanol, ethanol, isopropanol, 2-propanol, 1-butanol, t-butyl alcohol, 1- pentanol, 2-pentanol, acetone, butanone, 2-pentanone, 3-pentanone, methyl butyl ketone, methyl ethyl ketone, methyl isobutyl ketone, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, t-butyl acetate, isobutyl acetate, methylene dichloride, ethylene dichloride, acetonitrile, tetrahydrofuran, 1,4-dioxane, 2-methoxyethanol, diethyl ether, diisopropyl ether, methyl t-butyl ether or mixtures thereof. Step b) involves agitating the slurry by means of any suitable technique including stirrer bar, stir rod or shaker at any suitable temperature including reflux, room temperature, 0-5 °C or any other suitable temperature. Isolation of the product may be carried out under ambient conditions or in inert atmosphere (e.g. nitrogen). The product is a white or off white solid. In another aspect the present invention provides a process for the preparation of Compound 1 free base Form A comprising: a) providing a solution of Compound 1 free base in any suitable solvent; b) mixing the solution with an antisolvent to obtain a slurry; and c) agitating the slurry; and d) isolating Compound 1 free base Form A. The solvent employed in step a) and the antisolvent in step b) is selected from the group consisting of methanol, ethanol, isopropanol, 2-propanol, 1-butanol, t-butyl alcohol, 1- pentanol, 2-pentanol, acetone, butanone, 2-pentanone, 3-pentanone, methyl butyl ketone, methyl ethyl ketone, methyl isobutyl ketone, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, t-butyl acetate, isobutyl acetate, methylene dichloride, ethylene dichloride, acetonitrile, tetrahydrofuran, 1,4-dioxane, 2-methoxyethanol, diethyl ether, diisopropyl ether, methyl t-butyl ether or mixtures thereof. The temperature of the solution may be any suitable temperature e.g. reflux temperature of the solvent, 50 °C, 40 °C, room temperature etc. Mixing the solution in step b) might be carried out by dosing the solution to the antisolvent or by dosing the antisolvent to the solution. Dosing may be uncontrolled or controlled by means of any suitable technique. Step c) involves agitating the slurry by means of any suitable technique including stirrer bar, stir rod or shaker at or below the temperature set at step b). Isolation of the product may be carried out under ambient conditions or in inert atmosphere (e.g. nitrogen). The product is a white or off white solid. In another aspect the present invention provides a process for the preparation of Compound 1 free base Form B comprising: a) providing a solution of Compound 1 free base in any suitable solvent; b) mixing the solution with an antisolvent to obtain a slurry; and d) isolating Compound 1 Form B. The solvent employed in step a) and the antisolvent in step b) is selected from the group consisting of water, methanol, ethanol, isopropanol, 2-propanol, 1-butanol, t-butyl alcohol, 1-pentanol, 2-pentanol, acetone, butanone, 2-pentanone, 3-pentanone, methyl butyl ketone, methyl ethyl ketone, methyl isobutyl ketone, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, t-butyl acetate, isobutyl acetate, methylene dichloride, ethylene dichloride, acetonitrile, tetrahydrofuran, 1,4-dioxane, 2-methoxyethanol, diethyl ether, diisopropyl ether, methyl t-butyl ether or mixtures thereof. The temperature of the solution may be any suitable temperature e.g. reflux temperature of the solvent, 50 °C, 40 °C, room temperature etc. Mixing the solution in step b) might be carried out by dosing the solution to the antisolvent or by dosing the antisolvent to the solution. Dosing may be uncontrolled or controlled by means of any suitable technique. Isolation of the product may be carried out under ambient conditions or in inert atmosphere (e.g. nitrogen). The product is a white or off white solid. The X-ray diffraction pattern of Compound 1 Form B is shown on Figure 28. Detailed peak list is shown in Table 11. Most characteristic peaks of Compound 1 Form B are at 6.1, 16.0, 18.0, 19.2 and 21.5±0.2° 2θ. Table 11 X-ray diffraction peaks of Compound 1 Form B Compound 1 Form B can also be characterized by its FT-IR spectrum. The infrared spectrum of Form B is shown on Figure 29. Detailed list of absorption bands of Compound 1 Form B is shown in Table 12. Table 12. Infrared absorption bands of Compound 1 Form B Compound 1 Form B can also be characterized by its Raman spectrum. The Raman spectrum of Compound 1 Form B is shown on Figure 30. Detailed list of Raman peaks of Compound 1 Form B is shown in Table 13. Table 13. Raman peaks of Compound 1 Form B Compound 1 Form B can also be characterized by its DSC thermogram. A typical DSC thermogram of Compound 1 Form B is shown on Figure 31. Compound 1 Form B exhibits a broad exothermal between 100 and 200 °C before the melting endothermal with onset between 200 and 210 °C. In another aspect the present invention provides a process for the preparation of pyridine solvate of Compound 1 free base, Form C, by means of suspending Compound 1 maleate in pyridine, agitating and isolating Compound 1 free base, Form C as a white or off- white solid. Agitation involves agitating the slurry by means of any suitable technique including stirrer bar, stir rod or shaker at any suitable temperature including reflux, room temperature, 0-5 °C or any other suitable temperature. The X-ray diffraction pattern of Compound 1 free base, Form C is shown on Figure 32. Detailed peak list is shown in Table 14. Most characteristic peaks of Compound 1 free base, Form C are at 2.6, 5.3, 16.0, 19.4 and 24.7±0.2° 2θ. Table 14 X-ray diffraction peaks of Compound 1 free base, Form C Compound 1 free base, Form C can also be characterized by its DSC thermogram. A typical DSC thermogram of Compound 1 free base, Form C is shown on Figure 33. Compound 1 free base, Form C exhibits a broad endothermal between 50 and 150 °C before the melting endothermal with onset between 200 and 210 °C. A typical TGA thermogram of Compound 1 free base, Form C is shown on Figure 34. The weight loss of Form C is around 10% to 120 °C. Another aspect of the present invention is the hydrate form of Compound 1 free base, Form D. A further aspect of the present invention is the crystalline solid form of Compound 1 free base, comprising at least 5%, at least 10%, at least 20%, at least 40%, at least 60%, at least 80%, at least 90%, at least 95%, at least 99% of Compound 1 free base, Form D. The X-ray diffraction pattern of Compound 1 free base Form D is shown on Figure 35. Detailed peak list is shown in Table 15. Most characteristic peaks of Compound 1 free base Form D are at 8.1, 18.4, 18.8, 19.0 and 20.4±0.2° 2θ. Table 15 X-ray diffraction peaks of Compound 1 free base Form D Compound 1 free base Form D can also be characterized by its FT-IR spectrum. The infrared spectrum of Form D is shown on Figure 36. Detailed list of absorption bands of Compound 1 free base Form D is shown in Table 16. Most characteristic absorption bands of Compound 1 free base Form D are at 3515, 3243, 2869, 2829 and 1650±4 cm−1. Table 16 Infrared absorption bands of Compound 1 free base Form D Compound 1 free base Form D can also be characterized by its Raman spectrum. The Raman spectrum of Form D is shown on Figure 37. Detailed list of Raman peaks of Compound 1 free base Form D is shown in Table 17. Most characteristic Raman peaks of Compound 1 free base Form D are at 1644, 1552, 1539, 1301, 1257±4 cm−1. Table 17 Raman peaks of Compound 1 free base Form D Compound 1 free base Form D can also be characterized by its DSC thermogram. A typical DSC thermogram of Compound 1 free base Form D is shown on Figure 38. Compound 1 free base Form D exhibits a broad endotherm between 50 and 110 °C before the melting endothermal with onset between 200 and 210 °C. Compound 1 free base Form D is a hydrate form, its TGA thermogram exhibits a characteristic weight loss of 4.1% between 50 and 110 °C. A typical TGA thermogram of Compound 1 free base Form D is shown on Figure 39. The water content of the sample was confirmed by Karl Fisher titration (4.6%). In another aspect the present invention provides a process for the preparation of Compound 1 free base Form D comprising: a) providing a solution of Compound 1 free base in any suitable solvent; b) mixing the solution with water to obtain a slurry; and c) agitating the slurry; and d) isolating Compound 1 free base Form D. The solvent employed in step a) is selected from the group consisting of methanol, ethanol, isopropanol, 2-propanol, acetone, butanone, 2-pentanone, 3-pentanone, acetonitrile, tetrahydrofuran, 2-methoxyethanol, or mixtures thereof. The temperature of the solution may be any suitable temperature e.g. reflux temperature of the solvent, 50 °C, 40 °C, room temperature etc. Mixing the solution in step b) might be carried out by dosing the solution to the antisolvent or by dosing the antisolvent to the solution. Dosing may be uncontrolled or controlled by means of any suitable technique. Step c) involves agitating the slurry by means of any suitable technique including stirrer bar, stir rod or shaker at or below the temperature set at step b). Isolation of the product may be carried out under ambient conditions or in inert atmosphere (e.g. nitrogen). The product is a white or off white solid. For analytical studies, the following experimental conditions were used: Parameters of FT-IR spectroscopy measurements: Instrument: Thermo-Nicolet 6700 Phase: KBr pastille Spectral resolution: 4 cm-1Detector: DTGS Beamsplitter: XT-KBr Mirror movement speed: 0.6329 Number of scans: 100 Parameters of FT-Raman spectroscopy measurements: Instrument: Thermo-Nicolet NXR9650 Measurement range: 3500 to 200 cm-1Spectral resolution: 4 cm-1Detector: Ge Beamsplitter: CaF2 Mirror movement speed: 0.1581 Number of scans: 256 Laser performance: 500 mW Parameters of X-ray powder diffraction measurements: Instrument: PANanalytical X’Pert PRO MPD Radiation: CuKα Accelerating voltage: 40 kV Anode current: 40 mA Goniometer: PW3050 / 60 Scanning speed: 0.0305 s Increment: 0.0131 ° Sample holder: PW1818 / 25 & 40 (transmission, sample between foils) Sample holder spinner: PW3064 / 60 (reflection / transmission spinner) Spinning speed of sample holder: 1 spin / s Detector: PIXcel (PW3018 / 00) Uncertainty of the 2θ measurement: ± 0.2 ° Parameters of TGA measurements: Instrument: TA Instruments TGA Q5000 or Discovery TGA 5500 Heating rate: 10 °C / min Sample weight: ~ 2 to 10 mg Atmosphere: 60 mL / min N2 Parameters of DSC measurements: Instrument: TA Instruments DSC Q1000 or Discovery DSC 2500 Heating rate: 10 °C / min Sample weight: ~ 1 to 3 mg Pan type: open Al pan Atmosphere: 50 mL / min N2 Solubility method of analysis Approx.2-2 mgs (N=5) of the test substances were weighted in clear test vessels and 300 μL of solvent was added to them. The test vessels were placed in a mechanical shaker and shaken for the incubation time of 24 h at 37 °C, filtered and the concentration of Compound 1 in the filtrate was determined by HPLC-MS (Agilent1200 liquid chromatograph coupled with 6410 QQQ-MS, Kinetex EVO C18 column). HPLC method for analysis of purity Approx.10-10 mgs of the test substances were weighted in a 10 mL volumetric flask and were dissolved in a mixture of formic acid, acetonitrile and water.1 mL of this solution was diluted to 100 mL with the solvent mixture using a 100 mL volumetric flask. The diluted solution was then injected to a Waters Acquity H-Class UPLC instrument using an Acquity CSH coloumn. Physicochemical and biopharmaceutical characteristics of the active substance are critical in terms of in vivo and in vitro behaviour. Ideally, for an oral solid dosage form, a water soluble, nonhygroscopic, stable and easy processed crystalline compound is preferred for development purposes. Physicochemical and formulation related properties of the salt and crystalline forms of Compound 1 and its hydrochloride salt disclosed herein can be further characterized by the following methods: Crystal habit: Crystalline polymorphic materials can exist in a number of shapes or forms (sometimes called “habits”) depending on the method and solvent used for final crystallisation. This can range from highly angular crystals with an elongated shape, needle- like crystals and flat plate-like forms to more spherical habits. Their shape can affect the flowability of the bulk powder e.g. during discharge from containers / hoppers etc. due to particle–particle mechanical and physical interactions or cohesion. Shape of the drug particles can be characterized e.g. by polarized light microscopy (PLM). Particle size distribution: narrow range and monomodal particle size distribution of active pharmaceutical ingredients is advantageous from the aspect of drug formulation. Measurement of particle size distribution can be performed e.g. by laser diffraction method and polarized light microscopy. Specific surface area of the said solid forms can be determined by gas absorption (e.g. BET) or gas permeability methods. Dissolution: The solubility are important to select a salt form or a specific crystalline or polymorphic form that may affect dissolution rate, the most critical parameter. Dissolution is the process in which a substance forms a solution. Dissolution testing measures the extent and rate of solution formation from a dosage form, such as tablet, capsule, ointment, etc. The dissolution of a drug is important for its bioavailability and therapeutic effectiveness. Dissolution and drug release are terms used interchangeably. Differences in solubility and dissolution rate between polymorphs can have a pronounced impact on the oral bioavailability (dissolution and absorption from the GI tract) of pharmaceuticals. Flowability: While tablets and capsules, the two most common solid dosage forms, have their own unique requirements, there are similarities between them. They both require the flow of the correct weight of material into a specific volume. Good flow properties are a prerequisite for the successful manufacture of both tablets and powder-filled hard gelatin capsules or sachets. The European Pharmacopoeia (Ph. Eur.) contains a test on flowability of powders based on how a powder flows vertically out of a funnel. There are several different methods available for determining the flow properties of powders, and there are many literature examples demonstrating correlations between a test method and the manufacturing properties of a formulation. Bulk density is an essential parameter for pharmaceutical product & process development and solid dosage manufacturing. It is used in determining the amount of powder that can fit in a space such as a blender or a hopper on a tablet press or capsule filler. It is also used to determine the amount of powder that can be fitted into a capsule which has specific volume. Tapped bulk density, or simply tapped (tap) density is the maximum packing density of a powder (or blend of powders) achieved under the influence of well defined, externally applied forces. The minimum packed volume thus achieved depends on a number of factors including particle size distribution, true density, particle shape and cohesiveness due to surface forces including moisture. Therefore, the tap density of a material can be used to predict both its flow properties and its compressibility. The term “disease or condition associated with MCHR1 activity” refers to obesity, obesity related comorbid conditions and complications, diabetes, metabolic disorders, coronary artery disease, cerebrovascular disease, peripheral artery disease, hypertension, endocrine disorders, psychiatric conditions, personality disorders, eating disorders, sleep- wake cycle disorders, substance abuse and addictive disorders, chronic liver and kidney diseases, gastrointestinal disorders, chronic conditions of the musculo-skeletal system, osteoporosis, cancer. Reference is herein made to a parallel patent application filed by the applicant with the title of “MCHR1 antagonists for the treatment of Prader-Willi Syndrome” wherein the method of treating Prader-Willi Syndrome using the compounds of formula (I) according to WO 2016 / 166684 A1, such as Compound 1 in free form, or in a pharmaceutically acceptable salt form, e.g. hydrochloride salt thereof is disclosed. The term "pharmaceutical composition" refers to a mixture of Compound 1 Form A, Compound 1 Form D, Compound 1 hydrochloride salt, Compound 1 hydrochloride salt in crystalline form, or Compound 1 hydrochloride salt Form A with other chemical components, such as pharmaceutically acceptable excipients e.g., diluents or carriers. The pharmaceutical composition facilitates administration of the compound to the subject. The term "excipient" defines a chemical compound that facilitates the incorporation of a compound into cells or tissues. The pharmaceutical compositions of the present invention can be formulated in many ways, for instance as tablet, capsule, powder, granules, suspension, emulsion, solution, syrup, aerosol (with a solid or a liquid carrier) soft or hard gelatin capsule, suppository, injection in a steril form. Preferably, pharmaceutical composition is formulated as a tablet or a capsule. The pharmaceutical compositions can be in single dosage forms containing predetermined amount of active ingredient. This dosage can contain the therapeutically effective amount of Compound 1 Form A, Compound 1 Form D, Compound 1 hydrochloride salt, Compound 1 hydrochloride salt in crystalline form, or Compound 1 hydrochloride salt Form A or a given percentage of the therapeutically effective amount in such a way that these single dosage forms for repeated administration can be administered over a given period of time in order to reach the desired therapeutically effective dose. Preferred single dosage forms are those which contain the daily dose or sub-dose or – as it was mentioned above – a given percentage of the active ingredient. Furthermore, these pharmaceutical compositions can be manufactured in by methods known in the art. The term “therapeutically effective amount” refers to the amount of the active ingredient – compared to the subject, who did not receive such an amount – which results in the treatment, curing, prevention, alleviation or improvement of an illness, pathological condition, side-effect, one or more symptoms of a disease, such as hyperphagia, for maintaining or reducing body weight or for reducing food intake, or suppresses, or delay the degree of progression of an illness, pathological condition or one or more symptoms of a disease, such as hyperphagia. The term includes the effective amounts required for improving normal physiological functions as well. In the therapeutic applications Compound 1 Form A, Compound 1 Form D, Compound 1 hydrochloride salt, Compound 1 hydrochloride salt in crystalline form, or Compound 1 hydrochloride salt Form A can be administered in therapeutically effective amount as unformulated drug substances or the active ingredient can be formulated as medicament. The exact therapeutically effective amount of a such compound depends on several factors, including – but not exclusively – the age and the bodyweight of the treated subject (patient), the type and the seriousness of the disease to be treated, the type of the pharmaceutical composition / medicament and the way of administration. The term "daily dose" means the amount of free base administered per day. In case of administering pharmaceutically acceptable salts, daily dose is also expressed with the equivalent amount of free base. In an embodiment the therapeutically effective amount of Compound 1 Form A, Compound 1 Form D, Compound 1 hydrochloride salt, Compound 1 hydrochloride salt in crystalline form, or Compound 1 hydrochloride salt Form A, is a daily dose of at least about 2.5 mg. In another embodiment the therapeutically effective amount of Compound 1 Form A, Compound 1 Form D, Compound 1 hydrochloride salt, Compound 1 hydrochloride salt in crystalline form, or Compound 1 hydrochloride salt Form A, is a daily dose of from about 2.5 mg to about 22.5 mg. In a preferred embodiment, the therapeutically effective amount of Compound 1 Form A, Compound 1 Form D, Compound 1 hydrochloride salt, Compound 1 hydrochloride salt in crystalline form, or Compound 1 hydrochloride salt Form A, is a daily dose of from about 2.5 mg to about 7.5 mg. In a particularly preferred embodiment, the therapeutically effective amount of Compound 1 Form A, Compound 1 Form D, Compound 1 hydrochloride salt, Compound 1 hydrochloride salt in crystalline form, or Compound 1 hydrochloride salt Form A, is a daily dose of about 2.5 mg, about 5 mg or about 7.5 mg. The term “effective amount” refers to an amount of a drug or active ingredient which is sufficient, in the subject to which it is administered, to elicit the biological or medical response of a tissue, system, animal (including human) that is being sought, for instance, by a researcher or clinician. The term “subject” refers to a patient in need of any one of the methods 1.1 to 1.7 defined hereinafter. Compound 1 Form A, Compound 1 Form D, Compound 1 hydrochloride salt, Compound 1 hydrochloride salt in crystalline form, or Compound 1 hydrochloride salt Form A can be administered by any appropriate route, for example, by the oral, rectal, transdermal, subcutaneous, local, intravenous, intramuscular, or intranasal route. Preferable administration route is oral. In a series of further specific or alternative embodiments, the present invention provides: 1.1. A method for treating a disease or condition associated with MCHR1 activity, in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of Compound 1 Form A, Compound 1 Form D, Compound 1 hydrochloride salt, Compound 1 hydrochloride salt in crystalline form, or Compound 1 hydrochloride salt Form A as defined herein. 1.2. A method for treating Prader-Willi Syndrome, in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of Compound 1 Form A, Compound 1 Form D, Compound 1 hydrochloride salt, Compound 1 hydrochloride salt in crystalline form, or Compound 1 hydrochloride salt Form A as defined herein. 1.3. A method for improving, alleviating or delaying progression of one or more symptoms of PWS, in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of Compound 1 Form A, Compound 1 Form D, Compound 1 hydrochloride salt, Compound 1 hydrochloride salt in crystalline form, or Compound 1 hydrochloride salt Form A as defined herein. 1.4. A method for maintaining body weight in a patient afflicted with PWS, in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of Compound 1 Form A, Compound 1 Form D, Compound 1 hydrochloride salt, Compound 1 hydrochloride salt in crystalline form, or Compound 1 hydrochloride salt Form A as defined herein. 1.5. A method for reducing body weight in a patient afflicted with PWS, in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of Compound 1 Form A, Compound 1 Form D, Compound 1 hydrochloride salt, Compound 1 hydrochloride salt in crystalline form, or Compound 1 hydrochloride salt Form A as defined herein. 1.6. A method for reducing food intake in a patient afflicted with PWS, in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of Compound 1 Form A, Compound 1 Form D, Compound 1 hydrochloride salt, Compound 1 hydrochloride salt in crystalline form, or Compound 1 hydrochloride salt Form A as defined herein. 1.6. A method for treating hyperphagia in a patient afflicted with PWS, in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of Compound 1 Form A, Compound 1 Form D, Compound 1 hydrochloride salt, Compound 1 hydrochloride salt in crystalline form, or Compound 1 hydrochloride salt Form A as defined herein. 1.7. A method as indicated above, wherein the Compound 1 Form A, Compound 1 Form D, Compound 1 hydrochloride salt, Compound 1 hydrochloride salt in crystalline form, or Compound 1 hydrochloride salt Form A is administered once daily. 2. A pharmaceutical composition for use in any one of the methods 1.1 to 1.7, comprising Compound 1 Form A, Compound 1 Form D, Compound 1 hydrochloride salt, Compound 1 hydrochloride salt in crystalline form, or Compound 1 hydrochloride salt Form A as defined herein, together with one or more pharmaceutically acceptable excpients. 4. Compound 1 Form A, Compound 1 Form D, Compound 1 hydrochloride salt, Compound 1 hydrochloride salt in crystalline form, or Compound 1 hydrochloride salt Form A as defined herein, for use in any one of the methods 1.1 to 1.7. 5. Compound 1 Form A, Compound 1 Form D, Compound 1 hydrochloride salt, Compound 1 hydrochloride salt in crystalline form, or Compound 1 hydrochloride salt Form A as defined herein, for use in the preparation of a medicament for any one of the methods 1.1 to 1.7. 6. Use of Compound 1 Form A, Compound 1 Form D, Compound 1 hydrochloride salt, Compound 1 hydrochloride salt in crystalline form, or Compound 1 hydrochloride salt Form A as defined herein, for any one of the methods 1.1 to 1.7. In particular, the Compound 1 hydrochloride salt Form A as described herein is useful for treating hyperphagia in a patient afflicted with PWS. Further details of our invention are presented in the following examples, without limiting the scope of protection of the invention in any way to the examples mentioned. Unless it is specifically indicated in the individual examples, the starting materials of the following examples were prepared according to WO 2016 / 166684 Example 20(a) – Compound 1 free base, or 20(b) – Compound 1 maleate salt. Reference examples Reference example 1 Compound 1 maleate salt solvate from ethanol To a solution of 0.47 g (1.015 mmol) of Compound 1 (WO 2016 / 166684 Example 20 / a) in a 10:1 mixture of dichloromethane and methanol 0.13 g (1.117 mmol) of maleic acid was added and the mixture was concentrated. The residue was triturated with ethanol, and after 1 h stirring the solid product was filtered, washed with ethanol, and dried to yield 0.57 g (96%) of the title compound. XRPD pattern of the product is shown in Figure 1. TGA: 3.9% (Figure 10). Reference example 2 Compound 1 maleate salt solvate from ethanol 99.11 mg Compound 1 maleate was dissolved in 5 ml ethanol (jacket temperature 70 °C), filtered and the filtrate was cooled to 25 °C, agitated for 30 min, filtered and left to dry at room temperature for 4 days. XRPD pattern of the product is shown in Figure 2. TG: 5.1% (Figure 11) Reference example 3 Compound 1 maleate salt solvate from dichloromethane / ethanol 0.231 kg 4-[(5-chloropyridin-2-yl)methoxy]-l- {lH,2H,3H,4H,5H-[l,4]diazepino[l,7- a]indol-9-yl}-l,2-dihydropyridin-2-one (Example 4 in WO 2016 / 166684) was dissolved in 20 l acetonitrile, 0.3 kg K2CO3 and 520 ml 2-iodopropane was added and agitated at reflux for 10 h, and the product was isolated by evaporation of the solvent (100 mbar, 40-45 °C). The crude product was dissolved in 1.1 L dichloromethane and washed with 3×1 l water and the crude base was isolated by evaporation of the solvent (100 mbar, 40-45 °C). The solid was dissolved in 1.5 l dichloromethane and the solution of 65 g maleic acid in 3.6 l ethanol was added to it. The suspension was concentrated by evaporating 3.1 l solvent, 2 l ethanol was added and another 1.5 l was evaporated and the resulting suspension was agitated for an hour at 20-25 °C, cooled to 10-12 °C, agitated for an hour, filtered, washed with 2×0.5 l ethanol and dried at 75-80 °C for 7 hours to obtain 0.197 kg white solid. XRPD pattern of the product is shown in Figure 3. TGA: 4.1% (Figure 12). Reference example 4 Compound 1 maleate salt solvate from methanol 40 mg of maleate salt of Compound 1 was suspended in 1 ml methanol, agitated for a week, filtered and dried under ambient conditions. XRPD pattern of the product is shown on Figure 4. TGA: 5.5% (Figure 13). Reference example 5 Compound 1 maleate salt solvate from ethanol 40 mg of maleate salt of Compound 1 was suspended in 1 ml ethanol, agitated for a week, filtered and analysed by XRPD. XRPD pattern of the product is shown on Figure 5. TGA: 4.7% (Figure 14) Reference example 6 Compound 1 maleate salt solvate from ethanol To a solution of 0.47 g (1.015 mmol) of Compound 1 in 5 ml of a 10:1 mixture of dichloromethane and methanol the solution of 0.13 g maleic acid in 3.5 ml in the same solvent was added and the mixture was evaporated by means of Rotavapor (500-350 mbar, 40 °C). To the solid residue 1.9 ml ethanol was added, agitated for an hour, filtered and left to dry at room temperature. XRPD pattern of the product is shown on Figure 6. TGA: 1,9% (Figure 15) Reference example 7 Compound 1 maleate salt solvate from methanol 50 mg of maleate salt of Compound 1 was dissolved in 1 ml methanol and the solvent was evaporated at room temperature. XRPD pattern of the solid is shown on Figure 7. TGA: 4.3% (Figure 16). Reference example 8 Compound 1 maleate salt solvate from methanol 101 mg of maleate salt of Compound 1 was suspended in 2.5 ml methanol, agitated for a week, filtered and analysed by XRPD. XRPD pattern of the product is shown on Figure 8. The sample was dried at 40 °C overnight. TGA: 2.7% (Figure 17). Reference example 9 Compound 1 maleate salt solvate from DMSO 272 mg of the maleate salt of Compound 1 was suspended in 0.75 ml DMSO and agitated at room temperature for a week. The solid was filtered and analysed by XRPD. XRPD pattern of the product is shown on Figure 9. Reference example 10 0.6 g Compound 1 was dissolved in 5 ml of 95:5:0.1 mixture of dichloromethane, methanol and ammonia. The solvent was evaporated in Rotavapor (40 °C 500 mbar) to obtain 0.6 g off-white powder. Yield: 100%. XRPD of the product is shown in Figure 40. Examples Example 1 To the solution of 30 mg free base of Compound 1 in 1.2 ml acetone 7.5 µl 37% hydrochloric acid was added dropwise, agitated for 3 h, filtered and dried at 40 °C / vacuum. Yield: N / A. XRPD pattern of the product was in accordance with Figure 18 and the moisture content by TGA was 0.6% (to 200 °C). Example 2 To the solution of 3 g free base of Compound 1 in 36 ml dichloromethane a solution of 0.6 ml cc. hydrochloric acid in 36 ml acetone was added. The resulting suspension was cooled to 0 °C and agitated for 3 hours. The solid was filtered, washed with acetone and dried at 60 °C to obtain 3.10 g Compound 1 hydrochloride salt. Yield: 96%. XRPD pattern, FT-IR and FT-Raman spectra, DSC and TGA curves of the product are shown on Figure 18 to 22. Example 3 5.23 g crude Compound 1 free base was dissolved in a mixture of 30 ml dichloromethane, 15 ml ethanol and 15 ml toluene and concentrated by evaporation. The product was purified by column chromatography using Kieselgel 60 (0.040-0.063 mm) as adsorbent and 95:5:0.1 mixture of dichloromethane, methanol and cc. NH3 solution as eluent. The eluent was removed (Rotavapor) and the product was resuspended in ethanol, dried, resuspended in diethyl ether and filtered to yield 1.24 g white crystals. XRPD pattern of the product is shown in Figure 41 proving it to be a mixture of Compound 1 Form B and Compound 1 Form A. Example 4 100 mg Compound 1 free base, a mixture of Form A and Form B was suspended in 2 ml ethanol and agitated for a week at room temperature. The solid was filtered and identified by XRPD as Compound 1 Form A. Example 5 96.76 mg Compound 1 was dissolved in 11 ml ethanol at reflux, cooled down and agitated for approx.3 days to obtain a white precipitate identified as Compound 1 free base Form A. XRPD pattern of the product was in accordance with Figure 23. Example 6 83.5 mg Compound 1 free base was dissolved in 15 ml acetonitrile and stirred in open vial for two days, the solid was filtered to obtain a white to off-white precipitate identified as Compound 1 free base Form A. XRPD pattern of the product was in accordance with Figure 23. Example 7 1.17 g Compound 1 free base was dissolved in 13.2 ml dichloromethane and 2 ml of the solution was added to 2 ml tetrahydrofurane and agitated overnight to obtain a white precipitate identified as Compound 1 free base Form A. XRPD pattern of the product was in accordance with Figure 23. Example 8 1.17 g Compound 1 free base was dissolved in 13.2 ml dichloromethane and 2 ml of the solution was added to 2 ml methyl tertbutyl ether to obtain a white precipitate identified as Compound 1 free base Form B. XRPD pattern of the product was in accordance with Figure 28. Example 9 51.20 mg of Compound 1 maleate salt was suspended in 1.5 ml pyridine and agitated for a week. The solid was filtered and dried at 40 °C in vacuum to obtain Compound 1 free base Form C. XRPD pattern of the sample is shown on Figure 32, TGA: 10.3% (Figure 34). NMR: Compound 1 confirmed, with 0.4 mole pyridine and 0.15 mol maleic acid. Melting of Form A detected on DSC (Figure 33). Example 10 131.5 g Compound 1 free base was dissolved in 18.5 ml dichloromethane and 1.2 ml of this solution was added to 1 ml n-hexane spiked with 17 µl cc. HCl. The solid was filtered and dried at 40 °C. XRPD pattern of the sample is in accordance with Figure 35, confirmed as Compound 1 Form D. TGA: 4.1% (215 °C). Example 11 The solution of 1 g Compound 1 free base in 50 ml tetrahydrofurane at reflux was added to 150 ml water, agitated for an hour, filtered washed with water. XRPD pattern of the sample is in accordance with Figure 35. Preparation of pharmaceutical compositions The following formulation examples illustrate representative pharmaceutical compositions of this invention. The present invention however is not limited to the following pharmaceutical compositions. A) Solid oral dosage forms Tablets or Capsules or Filling sachets Active substance(s) 0.005 – 90% Filler 0.1 – 99.9% Binder 0 – 20% Disintegrant 0 – 20% Lubricant 0 – 10% Glidant 0 – 10% Other specific excipient(s) 0 – 50% B) Parenteral dosage forms Intravenous injections Active substance(s) 0.001 – 50% Solvent 10 – 99.9% Co-solvent 0 – 99.9% Osmotic agent 0 – 50% Buffering agent q.s. C) Other dosage forms Suppositories Active substance(s) 0.0003 – 50% Suppository base 1 – 99.9% Surface-active agents 0 – 20% Lubricant 0 – 20% Preservatives q.s.

Claims

Claims 1. A 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H- [1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one hydrochloride salt.

2. The salt of claim 1, wherein the salt is in crystalline form.

3. The salt of any one of claims 1 to 2, comprising 4-[(5-chloropyridin-2-yl)methoxy]- 1-[3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2- one hydrochloride salt Form A, characterized by one or more of the following solid state analytical properties: a, characteristic XRPD peaks are present as measured at CuKα wavelength at 9.2, 12.5, 14.5, 15.1, 15.8 and 17.4° 2θ (± 0.2°), and / or b, characteristic peaks are present in the Raman spectrum thereof in value ranges of 1549, 1344, 1303, 1257 and 747 cm−1± 4 cm-1, and / or c, characteristic absorption bands are present in the infrared spectrum thereof in value ranges of 2474, 2524, 1668, 1479 and 1222 cm-1(± 4 cm-1).

4. The salt of any one of the claims 1 to 3, comprising 4-[(5-chloropyridin-2-yl)methoxy]-1- [3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2- one hydrochloride salt Form A, having an XRPD pattern substantially similar to the XRPD pattern of Figure 18 as measured at CuKα wavelength.

5. The salt of any one of the claims 1 to 4, wherein the salt comprises at least 5% of 4-[(5- chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino [1,7- a]indol-9-yl]-1,2-dihydropyridin-2-one hydrochloride salt Form A.

6. The salt of any one of the claims 1 to 5, wherein the salt comprises at least 20% of 4-[(5- chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino [1,7- a]indol-9-yl]-1,2-dihydropyridin-2-one hydrochloride salt Form A.

7. The salt of any one of the claims 1 to 6, wherein the salt comprises at least at least 60% of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino [1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one hydrochloride salt Form A.

8. The salt of any one of the claims 1 to 7, wherein the salt comprises at least 80% of 4-[(5- chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino [1,7- a]indol-9-yl]-1,2-dihydropyridin-2-one hydrochloride salt Form A.

9. The salt of any one of the claims 1 to 8, wherein the salt comprises at least 95% of 4-[(5- chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino [1,7- a]indol-9-yl]-1,2-dihydropyridin-2-one hydrochloride salt Form A.

10. Crystalline 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H- [1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one free base Form A, characterized by one or more of the following solid state analytical properties: a, characteristic XRPD peaks are present as measured at CuKα wavelength at 5.9, 17.7, 18.1, 19.8 and 22.2° 2θ (±0.2°), and / or b, characteristic peaks are present in the Raman spectrum thereof in value ranges of 1554, 1345, 1267, 1260 and 750 cm-1± 4 cm-1, and / or c, characteristic absorption bands are present in the infrared spectrum thereof in value ranges of 1663, 1478, 1220, 860, 795 and 766 cm-1± 4 cm-1.

11. The crystalline 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H- [1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one free base Form A of claim 10, having an XRPD pattern substantially similar to the XRPD pattern of Figure 23 as measured at CuKα wavelength.

12. Crystalline solid form of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one, wherein the free base comprises at least 5% of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one free base Form A of any one of claims 10 to 11.

13. Crystalline solid form of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one, wherein the free base comprises at least 20% of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one free base Form A of any one of claims 10 to 12.

14. Crystalline solid form of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one, wherein the free base comprises at least 60% of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one free base Form A of any one of claims 10 to 13.

15. Crystalline solid form of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one, wherein the free base comprises at least 80% of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one free base Form A of any one of claims 10 to 14.

16. Crystalline solid form of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one, wherein the free base comprises at least 95% of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one free base Form A of any one of claims 10 to 15.

17. Crystalline 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H- [1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one free base Form D, characterized by one or more of the following solid state analytical properties: a, characteristic XRPD peaks are present as measured at CuKα wavelength at 8.1, 18.4, 18.8, 19.0 and 20.4° 2θ (±0.2°), and / or b, characteristic peaks are present in the Raman spectrum thereof in value ranges of 1644, 1552, 1539, 1301, 1257 cm-1± 4 cm-1, and / or c, characteristic absorption bands are present in the infrared spectrum thereof in value ranges of 3515, 3243, 2869, 2829 and 1650 cm-1± 4 cm-1.

18. The crystalline 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H- [1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one free base Form D of claim 17, having an XRPD pattern substantially similar to the XRPD pattern of Figure 35 as measured at CuKα wavelength.

19. Crystalline solid form of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one , wherein the free base comprises at least 5% of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one free base Form D of any one of claims 17 to 18.

20. Crystalline solid form of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one , wherein the free base comprises at least 20% of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one free base Form D of any one of claims 17 to 18.

21. Crystalline solid form of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one , wherein the free base comprises at least 60% of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one free base Form D of any one of claims 17 to 19.

22. Crystalline solid form of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one , wherein the free base comprises at least 80% of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one free base Form D of any one of claims 17 to 20.

23. Crystalline solid form of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one , wherein the free base comprises at least 95% of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one free base Form D of any one of claims 17 to 21.

24. A pharmaceutical composition comprising the hydrochloride salt or free base solid forms of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H- [1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one of claims 1 to 23 and a pharmaceutically acceptable carrier.

25. A method of preparing the salt of any one of claims 1 to 9 comprising: a) providing a solution of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one in any suitable solvent; b) mixing the solution is step a) with an HCl solution c) agitating the slurry; and d) isolating 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H- [1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one hydrochloride salt, wherein the solvent(s) employed in step a) and b) are selected from the group consisting of water, methanol, ethanol, isopropanol, 2-propanol, 1-butanol, t-butyl alcohol, 1-pentanol, 2- pentanol, acetone, butanone, 2-pentanone, 3-pentanone, methyl butyl ketone, methyl ethyl ketone, methyl isobutyl ketone, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, t- butyl acetate, isobutyl acetate, methylene dichloride, ethylene dichloride, acetonitrile, tetrahydrofuran, 1,4-dioxane, 2-methoxyethanol, diethyl ether, diisopropyl ether, methyl t- butyl ether or mixtures thereof.

26. The method of preparing the salt of any one of claims 1 to 9 comprising: a) providing a solution of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one HCl salt in any suitable solvent; b) evaporating part of the solvent to obtain a suspension; and c) agitating the slurry; andd) isolating 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H- [1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one HCl salt Form A, wherein the solvent employed in step a) is selected from the group consisting of water, methanol, ethanol, isopropanol, 2-propanol, 1-butanol, t-butyl alcohol, 1-pentanol, 2- pentanol, acetone, butanone, 2-pentanone, 3-pentanone, methyl butyl ketone, methyl ethyl ketone, methyl isobutyl ketone, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, t- butyl acetate, isobutyl acetate, methylene dichloride, ethylene dichloride, acetonitrile, tetrahydrofuran, 1,4-dioxane, 2-methoxyethanol, diethyl ether, diisopropyl ether, methyl t- butyl ether or mixtures thereof.

27. The method of preparing the salt of any one of claims 1 to 9 comprising: a) providing a solution of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one HCl salt in any suitable solvent; b) cooling the solution to obtain a slurry; and c) agitating the slurry; and d) isolating 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H- [1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one HCl salt Form A, wherein the solvent employed in step a) is selected from the group consisting of water, methanol, ethanol, isopropanol, 2-propanol, 1-butanol, t-butyl alcohol, 1-pentanol, 2- pentanol, acetone, butanone, 2-pentanone, 3-pentanone, methyl butyl ketone, methyl ethyl ketone, methyl isobutyl ketone, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, t- butyl acetate, isobutyl acetate, methylene dichloride, ethylene dichloride, acetonitrile, tetrahydrofuran, 1,4-dioxane, 2-methoxyethanol, diethyl ether, diisopropyl ether, methyl t- butyl ether or mixtures thereof.

28. The method of preparing the salt of any one of claims 1 to 9, comprising: a) providing a solution of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one HCl salt in any suitable solvent;b) mixing the solution with an antisolvent to obtain a slurry; and c) agitating the slurry; and d) isolating 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H- [1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one HCl salt Form A. wherein the solvent employed in step a) and the antisolvent in step b) are selected from the group consisting of water, methanol, ethanol, isopropanol, 2-propanol, 1-butanol, t-butyl alcohol, 1-pentanol, 2-pentanol, acetone, butanone, 2-pentanone, 3-pentanone, methyl butyl ketone, methyl ethyl ketone, methyl isobutyl ketone, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, t-butyl acetate, isobutyl acetate, methylene dichloride, ethylene dichloride, acetonitrile, tetrahydrofuran, 1,4-dioxane, 2-methoxyethanol, diethyl ether, diisopropyl ether, methyl t-butyl ether or mixtures thereof.

29. The method of preparing the crystalline solid form of 4-[(5-chloropyridin-2-yl)methoxy]- 1-[3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2- one comprising its free base Form A polymorph of any one of claims 10 to 16, comprising: a) providing a solution of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one in any suitable solvent; b) evaporating part of the solvent to obtain a suspension; and c) agitating the slurry; and d) isolating 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H- [1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one Form A, wherein the solvent used in step a) is selected from group consisting of water, methanol, ethanol, isopropanol, 2-propanol, 1-butanol, t-butyl alcohol, 1-pentanol, 2-pentanol, acetone, butanone, 2-pentanone, 3-pentanone, methyl butyl ketone, methyl ethyl ketone, methyl isobutyl ketone, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, t-butyl acetate, isobutyl acetate, methylene dichloride, ethylene dichloride, acetonitrile, tetrahydrofuran, 1,4- dioxane, 2-methoxyethanol, diethyl ether, diisopropyl ether, methyl t-butyl ether or mixtures thereof.

30. The method of preparing the crystalline solid form of 4-[(5-chloropyridin-2-yl)methoxy]- 1-[3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2- one comprising its free base Form A polymorph of any one of claims 10 to 16, comprising: a) providing a solution of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one in any suitable solvent; b) cooling the solution to obtain a slurry; and c) agitating the slurry; and d) isolating 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H- [1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one Form A. wherein the solvent used in step a) is selected from group consisting of water, methanol, ethanol, isopropanol, 2-propanol, 1-butanol, t-butyl alcohol, 1-pentanol, 2-pentanol, acetone, butanone, 2-pentanone, 3-pentanone, methyl butyl ketone, methyl ethyl ketone, methyl isobutyl ketone, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, t-butyl acetate, isobutyl acetate, methylene dichloride, ethylene dichloride, acetonitrile, tetrahydrofuran, 1,4- dioxane, 2-methoxyethanol, diethyl ether, diisopropyl ether, methyl t-butyl ether or mixtures thereof.

31. The method of preparing the crystalline solid form of 4-[(5-chloropyridin-2-yl)methoxy]- 1-[3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2- one comprising its free base Form A polymorph of any one of claims 10 to 16, comprising: a) providing a suspension of a solid form of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan- 2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one in any suitable solvent; b) agitating the slurry; and c) isolating 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H- [1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one Form A. wherein the solvent used in step a) is selected from group consisting of water, methanol, ethanol, isopropanol, 2-propanol, 1-butanol, t-butyl alcohol, 1-pentanol, 2-pentanol, acetone, butanone, 2-pentanone, 3-pentanone, methyl butyl ketone, methyl ethyl ketone, methylisobutyl ketone, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, t-butyl acetate, isobutyl acetate, methylene dichloride, ethylene dichloride, acetonitrile, tetrahydrofuran, 1,4- dioxane, 2-methoxyethanol, diethyl ether, diisopropyl ether, methyl t-butyl ether or mixtures thereof.

32. The method of preparing the crystalline solid form of 4-[(5-chloropyridin-2-yl)methoxy]- 1-[3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2- one comprising its free base Form A polymorph of any one of claims 10 to 16, comprising: a) providing a solution of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one in any suitable solvent; b) mixing the solution with an antisolvent to obtain a slurry; and c) agitating the slurry; and d) isolating 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H- [1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one Form A. wherein the solvent used in step a) and the antisolvent in step b) is selected from group consisting of methanol, ethanol, isopropanol, 2-propanol, 1-butanol, t-butyl alcohol, 1- pentanol, 2-pentanol, acetone, butanone, 2-pentanone, 3-pentanone, methyl butyl ketone, methyl ethyl ketone, methyl isobutyl ketone, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, t-butyl acetate, isobutyl acetate, methylene dichloride, ethylene dichloride, acetonitrile, tetrahydrofuran, 1,4-dioxane, 2-methoxyethanol, diethyl ether, diisopropyl ether, methyl t-butyl ether or mixtures thereof.

33. The method of preparing the crystalline solid form of 4-[(5-chloropyridin-2-yl)methoxy]- 1-[3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2- one comprising its free base Form D polymorph of any one of claims 17 to 23, comprising: a) providing a solution of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)- 1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one in any suitable solvent; b) mixing the solution with an antisolvent to obtain a slurry; and c) agitating the slurry; andd) isolating 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H- [1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one Form D. wherein the solvent used in step a) is selected from group consisting of methanol, ethanol, isopropanol, 2-propanol, acetone, butanone, 2-pentanone, 3-pentanone, acetonitrile, tetrahydrofuran, 2-methoxyethanol, or mixtures thereof.

34. Solid forms of 4-[(5-chloropyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H- [1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one or its hydrochloride salt according to claims 1 to 23, for use in the treatment / prevention of a disease or condition associated with melanin concentrating hormone receptor 1 activity.

35. Solid forms for use according to claim 34, wherein the disease or condition associated with melanin concentrating hormone receptor 1 activity is selected from the group consisting of obesity, obesity related comorbid conditions and complications, diabetes, metabolic disorders, coronary artery disease, cerebrovascular disease, peripheral artery disease, hypertension, endocrine disorders, psychiatric conditions, personality disorders, eating disorders, sleep-wake cycle disorders, substance abuse and addictive disorders, chronic liver and kidney diseases, gastrointestinal disorders, chronic conditions of the musculo-skeletal system, osteoporosis, cancer and Prader-Willi Syndrome.

36. Solid forms for use according to claim 35, wherein the disease or condition associated with melanin concentrating hormone receptor 1 activity is Prader-Willi Syndrome.

37. Solid forms for use according to claim 36 wherein the use provides improvement in one or more symptoms of Prader-Willi Syndrome.

38. Solid forms for use according to claim 37, wherein the one or more symptoms of Prader-Willi Syndrome is hyperphagia.

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