Patent HU-T62897-A (HU)
Title: Process for producing 2-carboxycarbapenem and carbacefem derivatives
Inventor: FEIGELSON GREGG BRIAN
IPC: C07D477/00
Filed: 1992-03-19
Abstract: 4-substd. azetidinone derivs. of formula (I) and (II) are new: R1 = H, OH(lower)alkyl or protected OH(lower)alkyl; R2 = H or 1-6C alkyl; R3 = H; halogen; azido; NO2; CN; a leaving gp. comprising OCOCH3, OCOCF3, OSO2CH3, OSO2Ph or OP(O)(OPh)2; S(O)iRa, where i = 0-2 and Ra = H, 1-6C alkyl, 3-7C cycloalkyl 2-6C alkenyl, 2-6C alkynyl, aryl, heteroaryl, aryl(1-6C)alkanoyl, arylcarbonyl, heteroarylcarbonyl, heterocyclyl, heterocyclyl(1-6C)alkyl, fused heterocyclyl, fused hetero-cyclyl(1-6C)alkyl, fused heteroaryl, fused heteroaryl(1-6C)alkyl, quaternized heteroaryl, quaternized heteroaryl(1-6C)alkyl, quaternized heterocyclyl, quaternized heterocyclyl(1-6C)alkyl, quaternized fused heterocyclyl, quaternized fused heterocyclyl(1-6C)alkyl, quaternized fused heteroaryl, quaternized fused heteroaryl(1-6C)alkyl, quaternized heterocyclyl(1-6C)thioalkyl, gps. being opt. substd. by 1-6C alkyl, NH2, 1-6C alkanoylamino, mono-, di- or tri-(1-6C)alkylamino, OH, 1-6C alkoxy, SH, 1-6C alkylthio, heteroarylthio, fused heteroarylthio, arylthio, heterocyclylthio, fused heterocyclylthio, sulphamoyl, carbamoyl, amidino, guanidino, NO2, F, Cl, Br, carboxy and salts or esters, 1-6C alkanoyloxy, arylcarbonyl, heteroarylcarbonyl, heterocyclylcarbonyl, fused heterocyclylcarbonyl, the heteroatom(s) in the heterocyclyl, fused heterocyclyl, heteroaryl and fused heteroaryl moieties are selected from 1-4 O, N and S and each ring of the heterocycle, fused heterocycle and heteroaryl, fused heteroaryl moieties is comprised of 5 or 6 atoms, the heteroatom(s) in the quaternized moieties above are selected from 1-4 O, N or S and must contain at least 1 N and each ring is comprised of 5 or 6 atoms; -NRhR1; -N(Rh)PRi; -N(Rh)NRhRi, a gp. of formula (i)-(viii): -NHSO2Rk; -N=C; -NCO; RhRiP(O)NH-; -NHCN; -NHP(O)Rh(OR1); Rh and Ri = H, opt. substd. 1-4C alkyl and 1-6C cycloalkyl, aryl, heterocyclyl, heterocyclyl(1-4C)alkyl, heteroaryl and heteroaryl(1-4C)alkyl where the heteroatom(s) are selected from 1-4 O, N and S, or Rh and Ri together may form a cyclic gp. with 5 or 6 ring atoms; and Rh and Ri or the cyclic radical formed between them is opt. substd. with NH2, mono-, di- or tri-(1-3C)alkylamino, OH, carboxyl, alkoxyl, -SO2NH2, Ph, benzyl or alkoxycarbonyl; Rk = H, opt. substd. 1-3C alkyl, 2-6C alkenyl, heterocyclyl or heteroaryl where heteroatom(s) are selected from 1-4 O, N and S and the cyclic portion has 5 or 6 ring atoms, and substits. on Rk are selected from NH2, mono-, di- and tri-(1-3C)alkylamino, OH, carboxyl, F, SO2NH2, carboxamido and alkoxycarbonyl; or R3 = -P(O)(ORi)(ORh); -P(O)(NRhRi)2; -P(O)(ORk)(NRiRh); -P(O)(N(Ri)-C(O)Rh)2; -P(O)(ORk)(NRiC(O)Rh); -C=C-Ra; -C(Rh)=N-Ri; -C(Ra)=S; -C(Rh)=C(R1)-Ra; -C(Ra)(Ri)-Rh; -CH2NRiRh; -CH2N(Rh)ORi; CH2N(Rk)NRhRi; -CH2F; -CH2Cl; -CHF2; -CH2Br; -CH2I; -CH2OCOCH3; -CH2N(Ri)C(O)Ri; -CH2-N(Rk)C(O)NRhRi; -CH2-C(NORk)C(O)NRhRi; -CH2NHSO2Rk; CH2NHP(O)(ORi)-(ORh); -CH2P(O)(ORi)(ORh); -CH2P(O)(ORi)(ORh); -CH2P(O)(NRhRi); -CHRkNRiRh; -CHRkN(Rh)ORi; -CHRkN(Rk)NRhRi; -CHCl2; -CHRkN(Rk)C(O)NRhRi; -CHRkC(NORk)C(O)NRhRi; -CHRkNHSO2Rk; -CHRkNHP(O)(ORi)-(ORh)-; -CHRkjP(O)(ORi)(ORh); R4 = H or a suitable removable protecting gp. for an amide N; R5 = H or a suitable removable protecting gp. for a carboxylic acid; X = O, S, NR6 where R6 = H, opt. branched (1-6C)alkyl, NR7 where R7 = OH, opt. branched (1-6C)alkoxy or silyloxy, or N-NR8R9 where R8 and R9 = H, (1-6C)alkyl, benzyl, Ph, CO2R5, or R8 and R9 together with the associated N form a 5 or 6-membered cycloalkyl ring. - Also claimed is the prepn. of carbapenems of formula (III) from (I) and carbacephems of formula (IV) from (II) by acid mediated ring closure.