CB-1267

Chemical Name: 1(S),3(R)-Dihydroxy-20(R)-[5,5,5-trifluoro-4-hydroxy-4-(trifluoromethyl)-2-pentynyloxymethyl]-9,10-secopregna-5(Z),7(E),10(19)-triene; (5Z,7E)-17beta-[1(R)-Methyl-2-[5,5,5-trifluoro-4-hydroxy-4-(trifluoromethyl)-2-pentynyloxy]ethyl]-9,10-secoandrosta-5,7,10(19)-trien-1alpha,3beta-diol
CAS No. 139174-97-3
项目整合开发状态: Preclinical
项目研究机构: Leo (Originator)
合成路线:Reduction of vitamin D derivative (I) with NaBH4 in ethanol-THF affords alcohol (II),which is alkylated with propargyl bromide (III) and potassium tert-butoxide in the presence of a crown ether.The resulting propargyl ether (IV) is condensed with hexafluoroacetone,by means of butyl litium,to provide tertiary alcohol (V).This compound is then photochemically isomerized in the presence of anthracene as a sensitizer to give (VI).Final deprotection of TBDMS groups with tetrabutylammonium fluoride in THF yields the title compound.

合成路线:Vitamin D derivative (I) was condensed with ethyllithium al low temperature to give,after chromatographic separation of isomers,alcohol (II).Alkylation of (II) with 6-bromo-3-ethyl-3-(trimethylsilyloxy)hexane (III) and potassium tert-butoxide in the presence of a crown ether afforded ether (IV),which was then photochemically isomerized in the presence of anthracene as a sensitizer to give (V).Final deprotection of silyl groups of (V) with 5% hydrogen fluoride in ethyl acetate-acetonitrile yielded the title compound.