Method for producing (4S)-4-[4-cyano-2-(methylsulfonyl)phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro pyrimidine-5-carbonitrile
The invention relates to a new and improved method for preparation of (4S)-4-[4-cyano-2-(methyl sulfonyl)phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro pyrimidine-5-carbonitrile of formula (I), as well as the preparation and use of the crystal form (A) of (4S)-4-[4-cyano-2-(methylsulfonyl)phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro pyrimidine-5-carbonitrile of formula (I).
1. A method for preparing a compound of formula (XXVII)
comprising:
a) reacting a compound of formula (XXVI)
in the presence of a cinchona alkaloid and a solvent to form compounds of formulas (XXVIII) and (XXIX)
b) isolating a compound of formula (XXVIII); and
c) reacting the compound of formula (XXVIII) in the presence of a strong acid to form a compound of formula (XXVII), where R 1 in the compound of formulas (XXVI), (XXVII), (XXVIII) and (XXIX) is hydrogen or methyl.
2. The method of claim 1 , wherein the cinchona alkaloid is chosen from the group consisting of quinine and quinidine.
3. The method of claim 1 wherein R 1 in the compound of formulas (XXVI), (XXVII), (XXVIII) and (XXIX) is hydrogen.
4. The method of claim 1 wherein R 1 in the compound of formulas (XXVI), (XXVII), (XXVIII) and (XXIX) is methyl.
5. A compound of formula (XXVII)
wherein the compound is a quinidine salt and R 1 is hydrogen or methyl.
6. The compound of claim 5 wherein R 1 is hydrogen.
7. The compound of claim 5 wherein R 1 is methyl.