反应详情

温度

80 °C

A solution of (S)-1-(4-methylbenzyl)-2-oxopyrrolidin-3-yl methanesulfonate (0.106 g, 0.375 mmol, from example 112, step D) in acetonitrile (1 mL) was added to a mixture of 2-fluoro-4-((3S,4S)-3-fluoropiperidin-4-yl)phenol (0.04 g, 0.188 mmol, from step E) and DIPEA (0.098 mL, 0.563 mmol) in acetonitrile (2 mL) heated at 80° C. The reaction mixture was then stirred at 80° C. for 16 h. The mixture was allowed to cool to rt and then concentrated in vacuo. The residue was purified using preparative LC/MS (Waters XBridge C18, 19×150 mm, 5 μm; Guard Column: Waters XBridge C18, 19×10 mm, 5 μm; Mobile Phase A: 5:95 acetonitrile:water with 10 mM NH4OAc; Mobile Phase B: 95:5 acetonitrile:water with 10 mM NH4OAc; Gradient: 15-60% B over 25 min, followed by a 10 min hold at 60% B and 5 min hold at 100% B; Flow: 15 mL/min). Fractions containing the desired product were combined concentrated in vacuo using a Genevac centrifugal evaporator to the titled compound of Example 115 (31 mg, 0.077 mmol, 41% yield) as pale yellow solid. LC-MS (M+H)+ 401; 1H NMR: (400 MHz, DMSO-d6) d=7.19-7.06 (m, 5H), 6.95-6.84 (m, 2H), 4.70-4.48 (m, 1H), 4.41-4.24 (m, 2H), 3.55 (s, 1H), 3.48-3.29 (m, 3H), 2.76-2.63 (m, 2H), 2.62-2.52 (m, 1H), 2.28 (s, 4H), 2.16-2.03 (m, 1H), 1.89 (s, 3H), 1.79-1.54 (m, 2H).

1. temperatureto cool to rt
2. concentrationconcentrated in vacuo
3. customThe residue was purified
4. waitGradient: 15-60% B over 25 min
5. waitfollowed by a 10 min
6. customat 60% B and 5 min
7. additionFractions containing the desired product
8. concentrationwere combined concentrated in vacuo