Methanol → tert-butyl (8R,9aR)-8-[(5-cyclopropylpyrazin-2-yl)oxy]-5-oxohexahydro-1H-pyrrolo[1,2-a][1,4]diazepine-2(3H)-carboxylate

Participants

Reaction Steps

tert-Butyl (8R,9aR)-8-hydroxy-5-oxohexahydro-1H-pyrrolo[1,2-a][1,4]diazepine-2(3H)-carboxylate (60 mg, 0.222 mmol, 1.0 equivalent, Example 46, Part D) was dissolved in tetrahydrofuran (1.0 mL). Potassium tert-butoxide (0.311 mL, 0.311 mmol, 1 M in tetrahydrofuran, 1.4 equivalents) was added at room temperature, and the resulting yellow solution was stirred for five minutes. Then 2-bromo-5-cyclopropylpyrazine (57.4 mg, 0.289 mmol, 1.3 equivalents) was added as a solution in tetrahydrofuran (0.5 mL), and the reaction mixture was stirred for 16 hours at the same temperature. The reaction mixture was quenched with 1 drop of saturated sodium bicarbonate, the solvent was removed in vacuo, and the crude material was loaded onto a 12 g silica column with 5% methanol/dichloromethane and eluted with 100:0 to 95:5 dichloromethane:methanol over 20 minutes to give the titled compound (50 mg, 0.129 mmol, 58.0% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 8.02 (s, 1H), 7.94 (d, J=1.1 Hz, 1H), 5.38 (br s, 1H), 4.23 (br s, 2H), 3.95 (t, J=7.2 Hz, 1H), 3.90-3.73 (m, 2H), 3.00 (br s, 2H), 2.71-2.45 (m, 3H), 2.18-1.86 (m, 2H), 1.47 (s, 9H), 1.05-0.85 (m, 4H); MS (ESI+) m/z 333.0 (M-tBu+H)+.

Provenance & Evidence