Diisopropylethylamine → N-(3-((4aS,5S,7aS)-2-amino-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-7a-yl)-4-fluorophenyl)-5-methoxypyrazine-2-carboxamide

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Reaction Steps

tert-Butyl((4aS,5S,7aS)-7a-(5-amino-2-fluorophenyl)-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)carbamate (Preparation Example 1, 56 mg) was dissolved in DCM (2 mL) and 5-methoxypyrazine-2-carboxylic acid (40 mg), N,N-diisopropylethylamine (80 mg) and (1H-benzotriazol-1-yloxy)tripyrrolidin-1-yl)phosphonium hexafluorophosphate (135 mg) were added. The reaction mixture was stirred at RT for 18 h, and sodium bicarbonate (sat., aq., 25 mL) was added. The mixture was extracted with EtOAc (2×40 mL), the combined organic portions were dried over MgSO4, evaporated and purified by silica gel chromatography (EtOAc/hexanes gradient) to afford the amide (40 mg) as a white solid. The amide was dissolved in DCM (2 mL) and TFA (1 mL) was added. After stirring at RT for 2 h, the reaction mixture was evaporated and sodium bicarbonate (sat., aq., 25 mL) was added. The mixture was extracted with EtOAc (2×25 mL), and the combined organic portions dried over MgSO4 and evaporated to afford the title compound as a white solid (34 mg). 1H NMR (400 MHz, CDCl3) δ ppm 2.78-2.87 (m, 1 H), 3.11-3.21 (m, 1 H), 3.38-3.48 (m, 1 H), 3.82-4.06 (m, 4 H), 4.48-4.72 (m, 2 H), 6.96-7.10 (m, 1 H), 7.52 (d, J=4.8 Hz, 1 H), 7.87 (d, J=8.8 Hz, 1 H), 8.09 (s, 1 H), 8.95 (s, 1 H), 9.46 (br. s., 1H)

Provenance & Evidence