Beta-lactamase inhibitor and process for preparing the same
A process for preparing a diazabicyclooctane compound represented by the following formula (I): wherein A represents RcO—; B represents NH or NC 1-6 alkyl; C represents a benzyl group; Rc represents a C 1-6 alkyl group; A is substituted with one substituent Fn1, wherein Fn1 represents an azetidine group; the process including: (a) silylating the compound represented by the following formula (IV-c): wherein in the formula (IV-c), OBn represents benzyloxy, and (b) carrying out an intramolecular urea formation reaction.
1. A process for preparing a diazabicyclooctane compound represented by the following formula (I):
wherein A represents RcO—; B represents NH or NC 1-6 alkyl; C represents SO 3 M, wherein M represents H, an inorganic cation or an organic cation; Rc represents a C 1-6 alkyl group; A is substituted with one substituent Fn1, wherein Fn1 represents an azetidine group; the process comprises:
(a) subjecting to coupling a compound represented by the following formula (IV-a):
wherein in the formula (IV-a), P 1 represents a protective group which can be removed by an acid, a base or a nucleophilic agent; and OBn represents benzyloxy, with a compound having the formula RcOBH in the presence of an active ester, an active amide or a dehydration condensing agent to prepare a compound represented by the following formula (IV-b):
wherein in the formula (IV-b), P 1 represents a protective group which can be removed by an acid, a base or a nucleophilic agent; and OBn represents benzyloxy,
(b) deprotecting P 1 to prepare a compound represented by the following formula (IV-c):
wherein in the formula (IV-c), OBn represents benzyloxy,
(c) silylating the compound of the formula (IV-c),
(d) carrying out an intramolecular urea formation reaction to prepare a compound represented by the following formula (IIa):
wherein in the formula (IIa), OBn represents benzyloxy,
(e) removing the benzyl group of the benzyloxy at the 6-position of the formula (IIa) in the presence of a hydrogenolysis catalyst under a hydrogen atmosphere to prepare a compound represented by the following formula (IIb):
and (f) sulfating the hydroxyl group at the 6-position of the formula (IIb) in the presence of a base, and optionally, deprotecting the protective group in the side chain RcOB—.
2. A process for preparing a diazabicyclooctane compound represented by the following formula (I):
wherein A represents RcO—; B represents NH or NC 1-6 alkyl; C represents a benzyl group; Rc represents a C 1-6 alkyl group; A is substituted with one substituent Fn1, wherein Fn1 represents an azetidine group; the process comprises:
(a) subjecting to coupling a compound represented by the following formula (IV-a):
wherein in the formula (IV-a), P 1 represents a protective group which can be removed by an acid, a base or a nucleophilic agent; and OBn represents benzyloxy,
with a compound RcOBH in the presence of an active ester, an active amide or a dehydration condensing agent to prepare a compound represented by the following formula (IV-b):
wherein in the formula (IV-b), P 1 represents a protective group which can be removed by an acid, a base or a nucleophilic agent; OBn represents benzyloxy,
(b) deprotecting P 1 to prepare a compound represented by the following formula (IV-c):
wherein in the formula (IV-c), OBn represents benzyloxy,
(c) silylating the compound of formula (IV-c), and
(d) carrying out an intramolecular urea formation reaction.