Process for the Manufacture of the Calcium Salt of Rosuvastatin (E)-7-[4-(4-Fluorophenyl)-6-Isopropyl-2-[Methyl(Methylsulfonyl)Amino]-Pyrimidin-5-yl](3R,5S)-3,5-Dihydroxyhept-6-Enoic Acid and Crystalline Intermediates Thereof
AssigneeAstraZeneca UK Limited
InventorsTetsuo OKADA, John HORBURY, David Dermot Patrick LAFFAN
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Abstract
A process for the manufacture of the calcium salt of (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid, useful as an HMGCoA reductase inhibitor, from a compound of the formula (7) wherein A is an acetal or ketal protecting group and R is alkyl, via isolated crystalline compounds of the formula (8) or of formula (10) is described. Crystalline intermediates of formulae 7, 8 and 10 are also described.
Claims16
A crystalline compound of formula (7),
- wherein A is an acetal or ketal protecting group and R is (1-6C)alkyl.
2-5. (canceled)
A crystalline compound of formula 8
- wherein R is (1-6C)alkyl.
(canceled)
A process for the manufacture of the calcium salt of (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid, comprising:
- a) acid hydrolysis of an acetal protecting group in a compound of formula (7)
- wherein A is an acetal or ketal protecting group and R is (1-6C)alkyl, and isolation of the resulting crystalline compound of formula (10);
- b) optional recrystallisation of the compound of the formula (10);
- c) hydrolysis of the compound of formula (10) to give a dihydroxy carboxylate derivative of formula (9, wherein M is a metal counterion other than calcium,
- or the calcium salt of (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid;
- and
- d) conversion of the compound of formula (9), where present, into the calcium salt of (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid.
Crystalline (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid-(3,6)-lactone having an X-ray powder diffraction pattern with peaks at 2-theta=7.9, 11.9, 15.9, 20.3, 21.7 and 22.5.
18-20. (canceled)
Dependencies are inferred from the claim text.