(3R,4R)-4-fluoropyrrolidin-3-ol → 6-(trans-3-Fluoro-4-hydroxypyrrolidin-1-yl)-5-(1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide
Reaction equation
Cl[C:2]1[C:21]([C:22]2[NH:26][N:25]=[CH:24][CH:23]=2)=[CH:20][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:11][CH:10]=2)=[O:7])=[CH:4][N:3]=1.[F:27][C@@H:28]1[CH2:32][NH:31][CH2:30][C@H:29]1[OH:33]>>[F:27][C@H:28]1[C@H:29]([OH:33])[CH2:30][N:31]([C:2]2[C:21]([C:22]3[NH:26][N:25]=[CH:24][CH:23]=3)=[CH:20][C:5]([C:6]([NH:8][C:9]3[CH:10]=[CH:11][C:12]([O:15][C:16]([F:19])([F:17])[F:18])=[CH:13][CH:14]=3)=[O:7])=[CH:4][N:3]=2)[CH2:32]1Participants
3
Procedure
The title compound was prepared in an analogous fashion to that described in Example 38 using 6-chloro-5-(1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 38.1) and trans-4-fluoropyrrolidin-3-ol (Stage 74.1). The product was purified by chromatography on Silica gel, preparative TLC (eluent EtOAc), followed by preparative SFC (Column 2-EP, from 17-22% in 6 min) to afford the title product as a white solid. UPLC-MS (Condition 8) tR=0.94 min, m/z=452.1 [M+H]+; 1H-NMR (600 MHz, DMSO-d6) δ ppm 3.07 (d, J=12.42 Hz, 1H) 3.30-3.51 (m, 2H) 3.56-3.74 (m, 1H) 4.17 (br. s, 1H) 4.86-5.00 (m, 1H) 5.42-5.52 (m, 1H) 6.38-6.46 (m, 1H) 7.35 (d, J=8.66 Hz, 2H) 7.53-7.91 (m, 3H) 8.03-8.13 (m, 1H) 8.71-8.82 (m, 1H) 10.24 (s, 1H).
Workup
- customThe title compound was prepared in an analogous fashion to
- customThe product was purified by chromatography on Silica gel, preparative TLC (eluent EtOAc)
- customfollowed by preparative SFC (Column 2-EP, from 17-22% in 6 min)
Sources & evidence
- ORD record
- ord-56008826c3664a8a9908dd35051a452f
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09340537B2
Reaction notes
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