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Crystalline forms of methyl 5-(((S)-2-amino-3-(4-carbamoyl-2,6-dimethylphenyl)-N-((S)-1-(4-phenyl-1H-imidazol-2-yl)ethyl)propanamido)methyl)-2-methoxybenzoate dihydrochloride Disclosure Number: IPCOM000245543D
Publication Date: 2016-Mar-16
Document File: 3 page(s) / 388K

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Page 01 of 3

Crystalline forms of methyl 5-(((S)-2-amino-3-(4-carbamoyl-2,6-dimethylphenyl)-N-((S)- 1-(4-phenyl-1H-imidazol-2-yl)ethyl)propanamido)methyl)-2-methoxybenzoate dihydrochloride

Methyl 5-(((S)-2-amino-3-(4-carbamoyl-2,6-dimethylphenyl)-N-((S)-1-(4-phenyl-1H- imidazol-2-yl)ethyl)propanamido)methyl)-2-methoxybenzoate dihydrochloride (referred to as Compound A) has the following structure

Compound A

Compound A is involved in the synthesis of 5-[[[(2S)-2-amino-3-(4-carbamoyl-2,6- dimethylphenyl) propanoyl]-[(1S)-1-(5-phenyl-1H-imidazol-2-yl)ethyl]amino]methyl]-2- methoxybenzoic acid (referred to as Compound B)

Compound A Compound B

Page 02 of 3

Preparation of crystalline 5-(((S)-2-amino-3-(4-carbamoyl-2,6-dimethylphenyl)-N-((S)-1-(4-

phenyl-1H-imidazol-2-yl)ethyl)propanamido)methyl)-2-methoxybenzoate dihydrochloride,

Compound A, Form III

Methyl-5-(((S)-2-((tert-butoxycarbonyl)amino)-3-(4-carbamoyl-2,6-dimethylphenyl)-N-((S)- 1-(4-phenyl-1H-imidazol-2-yl)ethyl)propanamido)methyl)-2-methoxybenzoate hydrochloride (750 g, 1.04mol) was charged in the reactor, followed by acetonitrile (4.0 L) addition. The suspension was cooled to 15-20 °C and hydrochloric acid (10.3 M, 1750 mL, 20.8mol, 20eq) was added maintaining temperature. The mixture is stirred for a minimum 4 hours at 15-20 °C, cooled to 0-5°C and stirred for additional period of minimum 5hours. The crystals were filtered off, washed extensively with acetonitrile and dried under vacuum at maximal temperature of 30°C till LOD < 20%. White crystals were identified as a methyl 5-(((S)-2- amino-3-(4-carbamoyl-2,6-dimethylphenyl)-N-((S)-1-(4-phenyl-1H-imidazol-2- yl)ethyl)propanamido)methyl)-2-methoxybenzoate dihydrochloride. The product was isol...