ChemicalBook CAS DataBase List Prasugrel

Prasugrel synthesis

10synthesis methods

Product Name:Prasugrel
CAS Number:150322-43-3
Molecular formula:C20H20FNO3S
Molecular Weight:373.44

Prasugrel (marketing name Effient in the US, Efient in the EU and Prasita in India) is a novel platelet inhibitor developed by Daiichi Sankyo Co. and produced by Ube and currently marketed in the United States in cooperation with Eli Lilly and Company for acute coronary syndromes planned for percutaneous coronary intervention (PCI). Prasugrel was approved for use in Europe in February 2009, and is currently available in the UK. On July 10, 2009, the US Food and Drug Administration approved the use of prasugrel for the reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with acute coronary syndrome who are to be managed with PCI.

Synthetic Routes

ROUTE 1

ROUTE 2

ROUTE 3

ROUTE 4

ROUTE 5

ROUTE 6

ROUTE 7

ROUTE 8

ROUTE 9

ROUTE 10

Padi, Pratap Reddy; Peri, Seetha Rama Sarma; Ganta, Madhusudhan Reddy; Polavarapu, Srinivas; Cherukupally, Praveen; Ireni, Babu; Padamata, Shailaja; Jonnada, Krishna; Vinigari, Krishna; Nerella, Kavitha. A process for preparing prasugrel and its salts and polymorphs. Assignee Dr. Reddy's Laboratories Ltd., India; Dr. Reddy's Laboratories, Inc. WO 2009062044. (2009).

5-[2-Cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-5,6,7,7a-tetrahydrothieno[3,2-c]pyridin-2(4H)-one

150322-38-6
122 suppliers
$158.08/250mg

75-36-5 Synthesis

75-36-5
578 suppliers
$17.92/100G

150322-43-3
348 suppliers
$8.00/25mg

Yield:150322-43-3 99%

Reaction Conditions:

Stage #1:5-(2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl)-5,6,7,7a-tetrahydrothieno[3,2-c]pyridin-2(4H)-one;acetyl chloride with acetic acid in toluene at 20;Inert atmosphere;
Stage #2: with sodium hydrogencarbonate in water;toluene

Steps:

12.B
Method BIn a 2 ltr 4-necked flask equipped with a thermometer and mechanical stirrer, 5-(a- cyclopropyIcarbonyl-2-fluoro-benzyl)-4,5,6,7-tetrahydrothieno -[3,2-c]-pyridine (100 g, 0.30 moles) was suspended in a mixture of toluene (400ml) and acetic acid (100 ml) under nitrogen atmosphere at 20 +/-5 °C and stir for 10 to 20 min. Slowly add acetyl chloride (180 g, 2.29 moles) in reaction mass at 20 +/-2 °C and stir for 12 to 16 hrs at 20 +/-2 °C. Quench the reaction mass into 30% sodium bicarbonate solution. Product extract with ethyl acetate (2 x 500 ml), organic layer washed with sodium chloride solution then water and dried over sodium sulfate. Recover the solvent under vacuum and crystalise the product in methanol, ethyl acetate, hexane or mixture thereof. Filter the product and slurry wash with methanol or ethyl acetate or hexane or mixture thereof. Dry the material at atmospheric pressure at 40-45 °C to obtain prasugrel (70 g, 99%). Method AIn a 2 ltr 4-necked flask equipped with a thermometer and mechanical stirrer, 2-(tert- Butyldimethylsilyloxy)-5-(a-cyclopropylcarbonyl-2-fluoro-benzyl)-4,5,6,7- tetrahydrothieno -[3,2-c]-pyridine (100 g, 0.22 moles) was suspended in a mixture of toluene (400ml) and acetic acid (100 ml) under nitrogen atmosphere at 20 +/-5 °C and stir for 10 to 20 min. Slowly add a solution of acetyl chloride (30 g, 0.38 moles) in acetic acid (140 ml) at 20 +/-2 °C. Stir the reaction mass for 4 to 6 hrs at 20 +/-2 °C. Slowly add acetyl chloride (180 g, 2.29 moles) in reaction mass at at 20 +/-2 °C and stir for 12 to 16 hrs at 20 +/-2 °C. Quench the reaction mass into 30% sodium bicarbonate solution. Product extract with ethyl acetate (2 x 500 ml), organic layer washed with sodium chloride solution then water and dried over sodium sulfate. Recover the solvent under vacuum and crystalise the product in methanol, ethyl acetate, hexane or mixture thereof. Filter the product and slurry wash with methanol or ethyl acetate or hexane or mixture thereof. Dry the material at atmospheric pressure at 40-45 °C to obtain prasugrel (80 g, 99%).

References:

MAYUKA LABS PVT. LTD.;KRISHNAMURTHY, Chandra, Sekhar, Nakka;SINGH, Jagat;KHAN, Mohd, Yunus WO2012/1486, 2012, A1 Location in patent:Page/Page column 23

FullText

952340-38-4 Synthesis