WO2015128882
CRYSTALLINE FORMS OF N-(2,4-DI-TERT-BUTYL-5-HYDROXYPHENYL)-1,4-DIHYDRO-4-OXOQUINOLINE-3-CARBOXAMIDE AND PROCESS FOR THE PREPARATION THEREOF
MSN LABORATORIES PRIVATE LIMITED
The present invention relates to crystalline forms ofN-(2,4-di-tert-butyl-5- hydroxyphenyl)-l,4-dihydro-4-oxoquinoline-3-carboxamide compound of formula- 1 and also process for the preparation of said compound of formula- 1 which is represented by the following structural formula:
Brief description of the invention:
The first aspect of the present invention is to provide a crystalline form of yV-(2,4-di-tert-butyl-5-hydroxy phenyl)- l,4-dihydro-4-oxoquinoline-3-carboxamide compound of formula- 1 (hereinafter designated as crystalline form-M).
The second aspect of the present invention is to provide a process for the preparation of crystalline form-M of N-(2,4-di-tert-butyl-5-hydroxy phenyl)- 1 ,4-dihydro-4-oxoquinoline-3-carboxamide compound of formula- 1.
The third aspect of the present invention is to provide a crystalline form of N-(2,4-di-tert-butyl-5-hydroxy phenyl)- l ,4-dihydro-4-oxoquinoline-3-carboxamide compound of formula- 1 (hereinafter designated as crystalline form-S).
The fourth aspect of the present invention is to provide a process for the preparation of crystalline form-S of N-(2,4-di-tert-butyl-5-hydroxy phenyl)- 1 ,4-dihydro-4-oxoquinoline-3-carboxamide compound of formula- 1.
The fifth aspect of the present invention is to provide a crystalline form of JV-(2,4-di-tert-butyl-5-hydroxy phenyl)- l,4-dihydro-4-oxoquinoline-3-carboxamide compound of formula- 1 (hereinafter designated as crystalline form-N).
The sixth aspect of the present invention is to provide a process for the preparation of crystalline form-N of 7V-(2,4-di-tert-butyl-5-hydroxy phenyl)- 1 ,4-dihydro-4-oxoquinoline-3-carboxamide compound of formula- 1.
The seventh aspect of the present invention is to provide an improved process for the preparation of N-(2,4-di-tert-butyl-5-hydroxyphenyl)- l ,4-dihydro-4-oxoquinoline-3-carboxamide compound of formula- 1.
The eighth aspect of the present invention is to provide a process for the preparation of crystalline form-B of N-(2,4-di-tert-butyl-5-hydroxyphenyl)-l ,4-dihydro-4-oxoquinoline-3-carboxamide compound of formula-1.
Examples:
Example-1: Preparation of N-(2,4-di-tert-butyI-5-hydroxyphenyl)-l,4-dihydro-4-oxo quinoline-3-carboxamide (formula-1)
A mixture of 4-oxo-l,4-dihydroquinoline-3-carboxylic acid (5 gm), N,N-dimethylformamide (50 ml), 1-Hydroxybenzotriazole (HOBT) (3.40 gm), l-Ethyl-3-(3-dimethyllaminopropyl)carbodiimide hydrochloride (EDC.HC1) (5.57 gm), 5-amino-2,4-di-tert-butylphenol (7.36 gm) and triethylamine (6 ml) was stirred for 52 hrs at 25-35° C. Distilled off the solvent completely under reduced pressure. Methanol (75 ml) was added to the obtained compound at 25-35° C and stirred for 45 min at the same temperature.
The reaction mixture was cooled to 0° C to 5° C and stirred for 60 min at the same temperature. Filtered the precipitated solid, washed with methanol and dried to get the ■ title compound.
Yield: 5 gm; Purity by HPLC: 99.5%.
The PXRD and DSC of the obtained compound are illustrated in figure- 1 and figure-5 respectively.
Claim:
1. A process for the preparation of N-(2,4-di-tert-butyl-5-hydroxyphenyl)-l ,4-dihydro-4- oxoquinoline-3 -carboxamide compound of formula-1 , comprising of reacting 4-oxo- l ,4-dihydroquinoline-3-carboxylic acid
with 5-Amino-2,4-di-tert-butylphenol
in presence of l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.HCl), hydroxybenzotriazole (HOBt) and a suitable base in a suitable solvent provides N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-l ,4-dihydroquinoline-3- carboxamide compound of formula-1 , optionally purifying the obtained compound from a suitable solvent provides pure compound of formula-1
Use of crystalline Form-M or Form-S or Form-N of N-(2,4-di-tert-butyl-5- hydroxyphenyl)-l,4-dihydro-4-oxoquinoline-3-carboxamide according to the preceding claims for the preparation of pharmaceutical composition.
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Dr MSN Reddy, Chairman and Managing Director, MSN Laboratories
MSN Laboratories Pvt.Ltd.
MSN House
Plot No: C-24
Industrial Estate, Sanathnagar
Hyderabad - 18 Telangana, INDIA
Phone : +91 40 30438600
Fax : +91 40 30438638
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