SY-726, SSY-726

Chemical Name: (-)-(R)-3-Methyl-3-(methylsulfonyl)-1-(1,2,4-triazol-1-yl)-2-[4-(trifluoromethyl)phenyl]-2-butanol
CAS No. 136067-88-4
项目整合开发状态: Discontinued
项目研究机构: Mitsubishi Pharma (Originator), SSP (Originator)
合成路线:The intermediate 2-(methylsulfanyl)-4'-(trifluoromethyl)isobutyrophenone (IV) was prepared by two alternative procedures.Reaction of bromo ketone (I) with sodium methanethiolate provided sulfide (II).Subsequent two step dimethylation of acetophenone (II) with CH3I and NaI gave rise to the isobutyrophenone (IV),through the intermediate propiophenone (III).

合成路线:In a different approach,addition of isopropylmagnesium bromide to 4-(trifluoromethyl)benzaldehyde (V) afforded alcohol (VI),which was further oxidized to the corresponding ketone (VII) by treatment with pyridinium chlorochromate.Bromination of 4'-(trifluoromethyl)isobutyrophenone (VII) in HOAc provided bromo ketone (VIII).Sulfide (IV) was then obtained by displacement of the bromide group of (VIII) with sodium methanethiolate.

合成路线:Condensation of isobutyrophenone (IV) with the lithium derivative of (S)-methyl p-tolyl sulfoxide (IX) produced alcohol (X) as a diastereomeric mixture.After chromatographic separation of the desired diastereoisomer,the methylsulfanyl group was selectively oxidized to sulfone (XI) with m-chloroperbenzoic acid.Reduction of the tolyl sulfoxide moiety of (XI) by means of NaI in the presence of acetyl chloride led to the corresponding sulfide (XII).Cyclization of the hydroxy sulfide (XII) to epoxide (XIII) was accomplished via S-alkylation with triethyloxonium tetrafluoroborate.Finally,opening of the chiral epoxide (XIII) with triazole (XIV) in the presence of K2CO3 furnished the title compound.