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Process for the preparation of (R)-5-(2-fluoro-3-methoxyphenyl)-1-(2-fluoro-6-(trifluoromethyl)benzyl)-6-methyl-3-(2-phenyl-2-(propan-2-ylideneamino)ethyl)pyrimidine-2,4(1H,3H)-dione

IP.com Disclosure Number: IPCOM000248042D
Publication Date: 2016-Oct-20
Document File: 1 page(s) / 289K

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                  Process for the preparation of (R)-5-(2-fluoro-3-methoxyphenyl)-1-(2-fluoro-6-(trifluoromethyl)benzyl)-6-methyl-3-(2- phenyl-2-(propan-2-ylideneamino)ethyl)pyrimidine-2,4(1H,3H)-dione

Disclosed herein after is a process for preparation of(R)-5-(2-fluoro-3-methoxyphenyl)-1-(2- fluoro-6-(trifluoromethyl)benzyl)-6-methyl-3-(2-phenyl-2-(propan-2-ylideneamino)ethyl) pyrimidine-2,4(1H,3H)-dione (referred herein as compound I).

1-(2-fluoro-6-(trifluoromethyl)benzyl)-5-iodo-6-methylpyrimidine-2,4(1H,3H)-dione (referred herein as Compound II) may be used in the preparation of Compound I. Compound I may be used in the preparation of Sodium 4-[[(1R)-2-[5-(2-fluoro-3-methoxyphenyl)-3-[[2- fluoro-6-(trifluoromethyl)phenyl]methyl]-4-methyl-2,6-dioxopyrimidin-1-yl]-1- phenylethyl]amino]butanoate and salts thereof.

Process for preparation of Compound II is described in US8765948.

Example 1: Preparation of Compound I

(R)-tert-butyl(2-(3-(2-fluoro-6-(trifluoromethyl)benzyl)-5-iodo-4-methyl-2,6-dioxo-2,3- dihydropyrimidin-1(6H)-yl)-1-phenylethyl)carbamate (referred to as compound A) is formed by N-alkylation of Compound II.

Compound II (11,68 mmol), K2CO3 (11,68 mmol), (R)-2-((tert-butoxycarbonyl) amino)-2- phenylethyl methanesulfonate (13,98 mmol) and tetra-n-butylammonium bromide (5,84 mmol) was suspended in toluene and water and stirred at increased temperature until completion. After cooling to ambient temperature, layers were separated and heptane was added at increased tempe...