Methyl(+)-(3-R)-7-[4-(4-Fluorophenyl)-6-isopropyl-2-(N-methyl-N-methanesul fonylamino) pyrimidin-5-yl]-3-hydroxy-5-oxo-6(E)-heptenoate Chemical Properties

Melting point:

103-107°C

Boiling point:

701.7±70.0 °C(Predicted)

Density 

1.311

storage temp. 

2-8°C

solubility 

DMSO (Slightly), Methanol (Slightly)

form 

Solid

pka

12.87±0.20(Predicted)

color 

Pale Yellow to Yellow

Methyl(+)-(3-R)-7-[4-(4-Fluorophenyl)-6-isopropyl-2-(N-methyl-N-methanesul fonylamino) pyrimidin-5-yl]-3-hydroxy-5-oxo-6(E)-heptenoate Usage And Synthesis

Uses

5-Oxorosuvastatin methyl ester is an intermediate in the synthesis of Rosuvasatatin (calcium salt: R700500), a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor that decreases high-sensitivity C-reactive protein (hsCRP) and cholesterol concentrations in the blood.

Synthesis

Under ice bath cooling conditions, 16 g of methyl 7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamido)-5-pyrimidinyl]-(3R)-tert-butyldimethylsilyloxy-5-oxo-(6E)-heptanoate (compound ii) was dissolved in 100 mL of acetonitrile. Subsequently, a 400 mL solution prepared from 48% hydrogen fluoride and acetonitrile at a volume ratio of 1:19 was slowly added dropwise. The reaction mixture was gradually warmed to room temperature and stirred continuously for 1.5 hours. Upon completion of the reaction, the reaction mixture was neutralized with sodium bicarbonate solution and subsequently extracted with ether. The organic layer was washed with aqueous sodium chloride solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. Eventually, the residual ether was removed by distillation to afford 13 g (yield: 100%) of the target product 7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidin-5-yl]-(3R)-3-hydroxy-5-oxo-(E)-6-heptenoic acid methyl ester (Compound iii) in the form of a syrupy substance.

References

[1] Patent: WO2006/17357, 2006, A1. Location in patent: Page/Page column 15
[2] Patent: WO2003/97614, 2003, A2. Location in patent: Page/Page column 8; 13
[3] Patent: CN104910078, 2017, B. Location in patent: Paragraph 0012; 0034; 0038-0040; 0046; 0052; 0058; 0064
[4] Bioorganic and Medicinal Chemistry, 1997, vol. 5, # 2, p. 437 - 444
[5] Patent: WO2006/91771, 2006, A2. Location in patent: Page/Page column 26

Methyl(+)-(3-R)-7-[4-(4-Fluorophenyl)-6-isopropyl-2-(N-methyl-N-methanesul fonylamino) pyrimidin-5-yl]-3-hydroxy-5-oxo-6(E)-heptenoate(147118-39-6)Related Product Information

• Rosuvastatin calcium