Producing 1,4-diphenylazetidinone derivatives useful as cholesterol resorption inhibitors from protected beta-substituted amino amides comprises using a quaternary phosphonium salt catalyst

摘要

Producing 1,4-diphenylazetidinone derivatives from protected beta -substituted amino amides in the presence of a silylating agent and a cyclization catalyst comprises using a catalyst comprising quaternary phosphonium cation and an organonitrogen anion or an alcoholate or carboxylate anion or a chloride, bromide or iodide anion in combination with silver(I) oxide. Producing 1,4-diphenylazetidinone derivatives from protected beta -substituted amino amides in the presence of a silylating agent and a cyclization catalyst comprises using a catalyst comprisi ng quaternary phosphonium cation of formula P +R 16R 17R 18R 19 (XII) and an organonitrogen anion of formula (VIII)-(XI or an alcoholate anion R 41O - or carboxylate anion R 42COO - or a chloride, bromide or iodide anion in combination with silver(I) oxide. R 16-R 19aryl, 1-15C alkyl or benzyl; Z : CO, CS, SO, SO 2 or C=NR 20; K : O, S, NR 21 or CR 22R 23; L : NR 24 or CR 25R 26; n : 0 or 1; M : O, CO, NR 27 or CR 28R 29; Q : O, S, NR 30, CR 31R 32, CO, CS, SO, SO 2 or C=NR 34; R : CR 35 or N; T : CR 36 or N; U : CR 37 or N; V : CR 38 or N; R 20-R 32, R 34-R 38H, 1-6C alkyl, aryl or heteroaryl, where pairs of alkyl groups can form 3-6C cycloalkylene groups optionally substituted with halo, CF 3, NO 2, COOR, CONRR, cycloalkyl, 1-10C alkyl, 2-6C alkenyl, OR, OCOR, O-CO-(1-6C)alkylene-Ar, SO 2NRR, SR, SR', SOR, SOR', SO 2R, SO 2R', SO 2NRR' or SO 2NR'R' or with NRR, NHCONHR, NHCONHAr', NRCOR, NRCOOR, NRCOAr', NRCOOAr', NRCONRR, NRCON(R)Ar', NRCONAr'Ar', NAr'COR, NAr'COOR, NAr'COAr', NAr'COOAr', NAr'CONRR, NAr'CON(R)Ar', NAr'CONAr'Ar', Ar' or O(CH 2) nAr'; R : 1-6C alkyl; R' : (CH 2) nAr; n : 0-6; Ar : aryl optionally substituted with 1-2 of F, Cl, Br, CF 3, SF 5, NO 2, OCF 3, OR or R; Ar' : aryl optionally substituted with 1-3 of halo, CF 3, NO 2, OCF 3, OR, R, NRR, SF 5, SO 2Me or COOR; R 39, R 401-6C alkyl in which nonadjacent C atoms can be replaced by NH or CO, 1-6C perfluoroalkyl, aryl or heteroaryl, or R 39+R 40 = 1,8-naphthyl or 1,7,7-trimethylbicyclo[2.2.1]heptanyl, or R 40 = H; R 41aryl, 1-14C alkyl or benzyl; R 421-15C alkyl, benzyl, 5-8C cycloalkyl, or aryl optionally substituted with halo, OH, OR", NH 2, NHR", NR"R", COOH, COOR", CONH 2, CONHR", CONR"R", SO 2NH 2, SO 2NHR", SO 2NR"R", CN, 1-12C alkyl or 5-8C cycloalkyl; R" : 1-3C alkyl. [Image] ACTIVITY : Antilipemic; Antiarteriosclerotic. MECHANISM OF ACTION : Cholesterol resorption inhibitor.