反应详情

A solution of (R)-1-(4-fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid (0.09 g) in N,N-dimethylformamide (1 mL) was treated with cesium carbonate (0.16 g) and 3-methyl-3-methylbromo-oxetane (0.14 g) at room temperature for 30 minutes. The reaction mixture was diluted with water and the precipitate collected by filtration and dried under vacuum. The solid was purified by preparative reverse-phase HPLC eluting with a mixture of methanol and water containing 0.1% formic acid (3:2 to 4:1 by volume) to give the title compound as a white solid (0.02 g). 1H NMR (400 MHz, CHCl3-d): δ 8.53 (d, 1H), 7.78 (dd, 1H), 7.49-7.41 (m, 3H), 7.16 (t, 2H), 6.62 (d, 1H), 6.45 (s, 1H), 4.49-4.38 (m, 3H), 4.34 (dd, 2H), 4.15 (s, 2H), 3.81 (t, 4H), 3.67 (t, 4H), 3.32 (d, 1H), 2.91 (d, 1H), 2.62 (d, 1H), 2.52 (d, 1H), 2.40 (d, 2H), 1.28 (s, 3H).

1. filtrationthe precipitate collected by filtration
2. customdried under vacuum
3. customThe solid was purified by preparative reverse-phase HPLC
4. washeluting with a mixture of methanol and water containing 0.1% formic acid (3:2 to 4:1 by volume)