1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → (R)-6-(3-Hydroxypyrrolidin-1-yl)-5-(1H-pyrazol-5-yl)-N-(6-((trifluoromethyl)thio)pyridin-3-yl)nicotinamide
Reaction equation
Br[C:2]1[C:3]([N:22]2[CH2:26][CH2:25][C@@H:24]([OH:27])[CH2:23]2)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:11]=[N:12][C:13]([S:16][C:17]([F:20])([F:19])[F:18])=[CH:14][CH:15]=1)=[O:8].O1CCCCC1[N:34]1[C:38](B2OC(C)(C)C(C)(C)O2)=[CH:37][CH:36]=[N:35]1>>[OH:27][C@@H:24]1[CH2:25][CH2:26][N:22]([C:3]2[C:2]([C:36]3[NH:35][N:34]=[CH:38][CH:37]=3)=[CH:21][C:6]([C:7]([NH:9][C:10]3[CH:11]=[N:12][C:13]([S:16][C:17]([F:20])([F:19])[F:18])=[CH:14][CH:15]=3)=[O:8])=[CH:5][N:4]=2)[CH2:23]1Participants
3
Reactant 2
Product 1
Procedure
The title compound was prepared in an analogous fashion to that described in Example 8 using (R)-5-bromo-6-(3-hydroxypyrrolidin-1-yl)-N-(6-((trifluoromethyl)thio)pyridin-3-yl)nicotinamide (Stage 32.1) and 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole to afford an off-white powder. HPLC (Condition 4) tR=4.18 min, UPLC-MS (Condition 3) tR=0.82 min, m/z=451.3 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.64-1.89 (m, 2H) 2.94 (d, J=11.73 Hz, 1H) 3.18-3.33 (m, 2H) 3.36-3.49 (m, 1H) 4.18 (br. s, 1H) 4.81 (d, J=3.13 Hz, 1H) 6.38 (s, 1H) 7.68-7.85 (m, 2H) 8.02 (d, J=1.95 Hz, 1H) 8.32 (dd, J=8.60, 2.35 Hz, 1H) 8.73 (d, J=2.35 Hz, 1H) 8.98 (d, J=2.35 Hz, 1H) 10.42 (s, 1H) 12.89-13.12 (m, 1H).
Workup
- customto afford an off-white powder
Sources & evidence
- ORD record
- ord-bec05d8806b94806b941a8bef02d6d2b
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08829195B2
Reaction notes
Loading…