Process for the preparation of rosuvastatin
AssigneeRanbaxy Laboratories Limited
InventorsYatendra Kumar, Hashim Nizar Poovanathil Neeran, Shantanu De, Mohammed Rafeeq, Swargam Sathyanarayana
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Abstract
The present invention relates to a process for the preparation of rosuvastatin calcium, a promising new HMG-CoA reductase inhibitor.
Claims33
A process for producing rosuvastatin of structural formula I,
- comprising:
- a. condensing 1-cyano (2S)-2-[(tert-butyldimethylsilyl)oxy]-5-oxo-6-triphenylphosphanylidene hexanenitrile of structural formula II
- with 4-(4-Fluorophenyl)-6-isopropyl-2-(N-methyl-N-methanesulfonylamino)-5-pyrimidinecarbaldehyde of structural formula III
- to give a condensed product of structural Formula IV,
- b. deprotecting the tert-butyidimethylsilyl group of the condensed product to afford a cyanoketo alcohol of structural formula V,
- c. reducing the cyanoketo alcohol to cyanodiol of structural formula VI, and
- d. hydrolyzing the cyanodiol of structural formula VI to produce said compound of structural formula I in free acid form, or in the form of an ester or lactone thereof, or in salt form.
The process of clam 1 wherein the deprotection at step (b) is performed by treating with acids or tetrabutylammonium fluoride.
A process for preparing a compound of structural formula VI
- comprising:
- a. condensing 1-cyano (2S)-2-[(tert-butyldimethylsilyl)oxy]-5-oxo-6-triphenylphosphanylidene hexanenitrile of structural formula II
- with 4-(4-Fluorophenyl)-6-isopropyl-2-(N-methyl-N-methanesulfonylamino)-5-pyrimidinecarbaldehyde of structural formula III
- to give a condensed product of structural formula IV,
- b. deprotecting the tert-butyldimethylsilyl group of the condensed product to afford a cyanoketo alcohol of structural formula V, and
- (c) reducing the cyanoketo alcohol of structural formula V to produce said compound of structural formula VI.
A process for preparing a compound of structural formula V
- comprising:
- (a) condensing 1-cyano (2S)-2-[(tert-butyidimethylsilyl)oxy]-5-oxo-6-triphenylphosphanylidene hexanenitrile of structural formula II
- with 4-(4-Fluorophenyl)-6-isopropyl-2-(N-methyl-N-methanesulfonylamino)-5-pyrimidinecarbaldehyde of structural formula III
- to give a condensed product of structural formula IV, and
- (b) deprotecting the tert-butyidimethylsilyl group of the condensed product to produce said compound of structural formula V.
A process for preparing a compound of structural formula
- comprising:
- condensing 1-cyano (2S)-2-[(tert-butyldimethylsilyl)oxy]-5-oxo-6-triphenylphosphanylidene hexanenitrile of structural formula II
- with 4-(4-Fluorophenyl)-6-isopropyl-2-(N-methyl-N-methanesulfonylamino)-5-pyrimidinecarbaldehyde of structural formula III
- to give a condensed product of structural formula IV.
A process for producing rosuvastatin of structural formula I comprising:
- (a) condensing 1-cyano (2S)-2-[(tert-butyldimethylsilyl)oxy]-5-oxo-6-triphenylphosphanylidene hexanenitrile of structural formula II
- with 4-(4-Fluorophenyl)-6-isopropyl-2-(N-methyl-N-methanesulfonylaminoy5-pyrimidinecarbaldehyde of structural formula III
- to give a condensed product of structural formula IV,
- (b) esterifying the condensed product to give an ester of a compound of structural formula IX,
- (c) reducing the ester to compound of structural formula X, and
- (d) hydrolyzing the compound of structural formula X to produce said compound of structural formula I in free acid form, or in the form of an ester or a lactone thereof, or in salt form.
A compound of structural formula II.
A compound of structural formula IV
A compound of structural formula V
A compound of structural formula VI
Dependencies are inferred from the claim text.