Browse Prior Art Database

Intermediates of (αS)-α-[[2-(4-morpholinyl)acetyl]amino]-benzenebutanoyl- L-leucyl-N-[(1S)-3-methyl-1-[[(2R)-2-methyl-2- oxiranyl]carbonyl]butyl]- L-αPhenylalaninamide

IP.com Disclosure Number: IPCOM000239050D
Publication Date: 2014-Oct-06
Document File: 4 page(s) / 181K

Publishing Venue

The IP.com Prior Art Database

This text was extracted from a Microsoft Word document.
At least one non-text object (such as an image or picture) has been suppressed.
This is the abbreviated version, containing approximately 53% of the total text.

Intermediates of (αS)-α-[[2-(4-morpholinyl)acetyl]amino]-benzenebutanoyl-L-leucyl-N-[(1S)-3-methyl-1-[[(2R)-2-methyl-2- oxiranyl]carbonyl]butyl]- L-αPhenylalaninamide

(aS)-a-[(4-morpholinylacetyl)amino]benzenebutanoyl-L-leucyl-N-[(1S)-3-methyl-1-[[(2R)-2-methyloxiranyl]carbonyl]butyl]-L-phenylalaninamide (referred to as Compound I) has the following structure:

Compound I

Described herein below, is a crystalline form of (αS)-α-[[(1,1-dimethylethoxy)carbonyl]amino]benzenebutanoyl-L-leucyl- L-phenylalanine phenylmethyl ester (referred to as compound A), and a crystalline form of (αS)-α-aminobenzenebutanoyl-L-leucyl-L-phenylalanine phenylmethyl ester, 2,2,2-trifluoroacetate  (referred to as compound B), which are intermediates for preparation of compound I.

Compound A

Compound B

Preparation of crystalline(αS)-α-[[(1,1 dimethylethoxy)carbonyl]amino]benzenebutanoyl-L-leucyl-L-phenylalanine phenylmethyl ester (compound A)

Crude (αS)-α-[[(1,1-dimethylethoxy)carbonyl]amino]benzenebutanoyl-L-leucyl-L-phenylalanine phenylmethyl ester can be prepared, for example, according to processes described in US7232818, Example 7. The obtained crude material (10g) was dissolved in MeOH (20ml) and MTBE (16ml) was added, resulting in the formation of a precipitate. The mixture was stirred at 35°C for 0.5h then at 0°C for 2h. The solid material was isolated by filtration, affording a crystalline form of(αS)-α-[[(1,1-dimethylethoxy)carbonyl]amino]benzenebutanoyl-L-leucyl- L-phenylalanine phenylmethyl ester. The obtained material was dried at 40°C for 16h.

The obtained product was characterized by XRPD pattern. The XRPD pattern is presented in the following representative X-ray diffractogram:

Main XRD peaks of compound A are: 3.8, 7.6, 7.8, 10.7, 14.8, 15.2, 17.5, 18.7, 20.4, 21.4, 22.4 and 27.5 ± ...