CLOPIDOGREL RELATED COMPOUND A (20 MG) ((S)-(O-CHLOROPHENYL)-6,7-DIHYDROTHIENO[3,2-C]PYRI-DINE-5(4H)-ACETIC ACID, HYDROCHLORIDE)

Uses

Clopidogrel Carboxylic Acid Hydrochloride (Clopidogrel EP Impurity A; Clopidogrel Impurity A; Clopidogrel USP A) is the hydrochloride salt of a metabolite of the drug Clopidogrel.

Synthesis

Example 6: Preparation of (S)-(+)-α-(2-chlorophenyl)-6,7-dihydro-4H-thieno[3,2-c]pyridine-5-acetic acid hydrochloride (Formula (III) hydrochloride) 1. 61 g of (S)-(+)-α-(2-chlorophenyl)-6,7-dihydro-4H-thieno[3,2-c]pyridine-5-acetic acid (the product of Example 5) was dissolved in a solvent mixture of 300 mL of acetone and 15 mL of methanol, and was heated to 40° C. to dissolve completely. 2. 16.4 mL of concentrated hydrochloric acid was slowly added to the above solution, after which the reaction mixture was stirred continuously at room temperature for 2 hours. 3. the reaction mixture was cooled to below 5 °C and kept at this temperature for at least 2 hours to promote crystallization. 4. The precipitated crystals were collected by filtration, washed with 100 mL of cold acetone and subsequently dried under reduced pressure at 40 °C to afford 61 g of the title compound as a white to pale yellow solid (yield: 90%). Product Characterization. - Melting point: 200-201°C - Spin: [α]D20 +64.87° (c=1%, MeOH) - Optical purity: 99.5% ee (HPLC) - 1H-NMR (DMSO-d6, ppm): δ 3.10 (s, 3H), 3.47 (s, 2H), 4.30 (s, 2H), 5.54 (s, 1H), 6.91 (d, 1H, J=4.8Hz), 7.44 (d, 1H, J=4.8Hz), 7.46-7.58 (m, 2H), 7.65 (d, 1H, J=7.4Hz), 7.65 (d, 1H, J=7.4Hz), 7.65 (d, 1H, J=7.4Hz). J=7.4 Hz), 7.97 (d, 1H, J=7.1 Hz) - 13C-NMR (DMSO-d6, ppm): δ 21.78, 48.81, 50.17, 65.43, 125.04, 125.54, 127.99, 128.29, 128.36, 130.37, 130.46, 131.49, 132.02, 134.43, 167.53 - IR (KBr, cm-1): 3435, 3114, 1728

References

[1] Patent: US2008/214821, 2008, A1. Location in patent: Page/Page column 5
[2] Patent: WO2006/137628, 2006, A1. Location in patent: Page/Page column 13