Stable bioavailable crystalline form of cefdinir and a process for the preparation thereof
AssigneeLupin Limited
InventorsGirij Singh, Himadri Sen, Dhananjai Srivastava, Himanshu Godbole, Gurvinder Singh, Pravin Mahajan, Umesh Rananaware, Sagar Nehate, Sanjay Wagh
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Abstract
The present invention relates to a stable and bioavailable crystalline form of a third generation cephalosporin antibiotic, cefdinir and a process for the preparation thereof. The present invention also relates to a pharmaceutical composition containing the novel crystalline cefdinir, useful in the treatment of maladies such as bacterial infections.
Claims26
(canceled)
A process for the preparation of a crystalline form of cefdinir comprising:
- (a) reacting a crystalline compound of formula (II)
- wherein M is an alkali metal, with a chlorinating or brominating agent in the presence of a water-immiscible organic solvent and in the presence of an organic base to produce a compound of formula (IV),
- wherein X is Cl or Br,
- (b) reacting the compound of formula (IV) with a compound of formula (III),
- wherein R1 is a trialkylsilyl protective group or a carboxylic acid protective group;
- and R2 is a trialkyl silyl group or a organic sulfonic acid, to produce a compound of formula (VII),
- wherein R1 is a trialkylsilyl protective group or a carboxylic acid protective group,
- (c) placing the compound of formula (VII) in a hydrocarbon solvent,
- (d) reacting the compound of formula (VII) with a second acid to remove the protective groups and produce a crude cefdinir product (I), either as a free base or as a salt of said second acid, and
- (e) crystallizing the crude cefdinir product (I) to produce a crystalline form of cefdinir (I).
A process for the preparation of a crystalline form of cefdinir comprising:
- (a) reacting a crystalline compound of formula (II)
- wherein M is an alkali metal, with a chlorinating agent in the presence of a dialkylaminopyridine and an alkali metal bromide in the presence of a water-immiscible organic solvent and in the presence of an organic base to form the corresponding acid bromide of formula (IV), wherein X is Br,
- (b) reacting the compound of formula (IV) with a compound of formula (III),
- wherein R1 is a trialkylsilyl protective group or a carboxylic acid protective group;
- and R2 is a trialkyl silyl group or a organic sulfonic acid, to produce a compound of formula (VII),
- wherein R1 is a trialkylsilyl protective group or a carboxylic acid protective group,
- (c) placing the compound of formula (VII) in a hydrocarbon solvent,
- (d) reacting the compound of formula (VII) with a second acid to remove the protective groups and produce a crude cefdinir product (I), either as a free base or as a salt of said second acid, and
- (e) crystallizing the crude cefdinir product (I) to produce a crystalline form of cefdinir (I).
26-31. (canceled)
Dependencies are inferred from the claim text.