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

Patent metadata

Field	Value
Publication number	US-9371291-B2
Application number	US-201113186363-A
Country	US
Kind code	B2
Filing date	Jul 19, 2011
Priority date	Oct 24, 2003
Publication date	Jun 21, 2016
Grant date	Jun 21, 2016

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.

First claim

The invention claimed is:

1. A crystalline compound of formula (7),

wherein
A is a ketal protecting group, and
R is (1-6C)alkyl,
which is methyl (E)-(6-{2-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]-pyrimidin-5-yl]vinyl}(4R,6S)-2,2-dimethyl[1,3]dioxan-4-yl)acetate having an X-ray powder diffraction pattern with peaks at 2-theta=9.5, 13.6 and 17.5.

2. A crystalline compound of formula (7),

wherein
A is a ketal protecting group, and
R is (1-6C)alkyl,
which is ethyl (E)-(6-{2-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]-pyrimidin-5-yl]vinyl}(4R,6S)-2,2-dimethyl[1,3]dioxan-4-yl)acetate having an X-ray powder diffraction pattern with peaks at 2-theta=15.9, 18.4 and 19.5.

3. A crystalline compound of formula (7),

wherein
A is a ketal protecting group, and
R is (1-6C)alkyl,
which is iso-propyl (E)-(6-{2-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]-pyrimidin-5-yl]vinyl}(4R,6S)-2,2-dimethyl[1,3]dioxan-4-yl)acetate having an X-ray powder diffraction pattern with peaks at 2-theta=7.8, 11.6 and 15.5.

4. A crystalline compound of formula (7),

wherein
A is a ketal protecting group, and
R is (1-6C)alkyl,
which is n-hexyl (E)-(6-{2-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]-pyrimidin-5-yl]vinyl}(4R,6S)-2,2-dimethyl[1,3]dioxan-4-yl)acetate having an X-ray powder diffraction pattern with peaks at 2-theta=5.3, 7.1 and 18.9.

Assignees

• Okada Tetsuo
• Horbury John
• Laffan David Dermot Patrick
• Astrazeneca Uk Ltd
• Shionogi & Co

Inventors

• Okada Tetsuo
• Horbury John
• Laffan David Dermot Patrick

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title

• C07D239/42 Primary

  One nitrogen atom (nitro radicals C07D239/30) · CPC title

• Y02P20/55

  Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups · CPC title