Réaction #164776

Équation de réaction

methanol

hydrogen chloride

diethyl ether

Racemic N-[3-[2-amino-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a-yl]-4-fluoro-phenyl]-5-fluoro-pyridine-2-carboxamide

methanol

methanol

→

title compound

Rendement 38.0%

N-[3-[(4aR,7aS)-2-Amino-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a-yl]-4-fluoro-phenyl]-5-fluoro-pyridine-2-carboxamide hydrochloride

Rendement 38.0%

Solvants

CO2

CO2

dichloromethane

Conditions de réaction

Traitement

1. 1
   AutreThe solvent is removed in vacuo

Mode opératoire

Racemic N-[3-[2-amino-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a-yl]-4-fluoro-phenyl]-5-fluoro-pyridine-2-carboxamide (451 mg, 929 μmol) is chirally purified by SFC (Column: Chiralcel OD-H (5 um), 2.1×25 cm; eluent: 40% methanol (0.2% isopropylamine) in CO2; flow 70 mL/min at UV 225 nm). Chiral analysis of the first eluting isomer: Column: Chiralcel OD-H (5 μm), 4.6×150 mm; eluent: 40% methanol (0.2% isopropylamine) in CO2; flow 5 mL/min at UV 225 nm confirms the enantiomerically enriched (>99% ee) enantiomer with Rt=1.01 minutes (175 mg, 360 μmoles). This material (free base, isomer 1) is dissolved in dichloromethane (1 mL) and methanol (0.5 mL) and 1 M hydrogen chloride in diethyl ether (0.36 mL, 360 μmoles) is added. The solvent is removed in vacuo to give the title compound (183 mg, 38%). ES/MS (m/e): 486 (M+H).

Source