Sodium Hydroxide → N-[3-[(4aR,7aS)-2-Benzamido-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a-yl]-4-fluoro-phenyl]-5-cyano-pyridine-2-carboxamide

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Reaction Steps

N-[(4aR,7aS)-7a-(5-Amino-2-fluoro-phenyl)-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (0.180 g, 0.39 mmol, isomer 1) is dissolved in a mixture of dichloromethane (2 mL) and DMF (0.25 mL). 5-Cyanopyridine-2-carboxylic acid (114 mg, 0.77 mmol), 1-hydroxybenzotriazole (106 mg, 0.77 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (150 mg, 0.77 mmol) are added and the reaction is stirred at room temperature overnight. The mixture is diluted with water (10 mL), ethyl acetate (10 mL) and added to a solution of 1 N NaOH (100 mL). The mixture is extracted with EtOAc (2×100 mL) and the organic layers are combined and washed with brine. The organic layer is dried over MgSO4, filtered and concentrated. The residue is purified over silica gel chromatography using a 0-100% ethyl acetate/hexanes gradient to give the title compound (133 mg, 57%). ES/MS (m/e): 597 (M+H).

Provenance & Evidence