4-bromo-N,N-dibutyl-5-methyl-1H-pyrazole-3-carboxamide → Benzyl 4-(4-bromo-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate
Reaction equation
[Br:1][C:2]1[C:3]([C:8]([N:10]([CH2:15][CH2:16][CH2:17][CH3:18])[CH2:11][CH2:12][CH2:13][CH3:14])=[O:9])=[N:4][NH:5][C:6]=1[CH3:7].F[C:20]1[CH:35]=[CH:34][C:23]([C:24]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:25])=[CH:22][C:21]=1[C:36]([N:38]1[CH2:47][CH2:46][C:45]2[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=2)[CH2:39]1)=[O:37]>>[Br:1][C:2]1[C:3]([C:8](=[O:9])[N:10]([CH2:11][CH2:12][CH2:13][CH3:14])[CH2:15][CH2:16][CH2:17][CH3:18])=[N:4][N:5]([C:20]2[CH:35]=[CH:34][C:23]([C:24]([O:26][CH2:27][C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)=[O:25])=[CH:22][C:21]=2[C:36]([N:38]2[CH2:47][CH2:46][C:45]3[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=3)[CH2:39]2)=[O:37])[C:6]=1[CH3:7]Participants
Reactant 2
Product 1
Procedure
Following a procedure analogous to that for the synthesis of Intermediate 1E, 4-bromo-N,N-dibutyl-5-methyl-1H-pyrazole-3-carboxamide (Intermediate 163A, 268 mg, 0.85 mmol) and benzyl 4-fluoro-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate (Intermediate 122B, 300 mg, 0.77 mmol) were converted to the title compound (215 mg, 41%). 1H NMR (DMSO-d6, 2:1 mixture of amide rotamers) δ 8.21 (dd, J=8.3, 1.9 Hz, 1H), 8.11 (d, J=2.0 Hz, 0.5H), 8.08-8.03 (m, 0.5H), 7.85-7.78 (m, 1H), 7.55-7.33 (m, 5.5H), 7.25-7.06 (m, 3H), 7.05-6.96 (m, 0.5H), 5.47-5.32 (m, 2H), 4.82-4.42 (m, 2H), 3.92-3.71 (m, 0.5H), 3.58-3.34 (m, 3H), 3.23-2.91 (m, 2.5H), 2.82-2.74 (m, 2H), 2.27 (s, 2H), 2.22 (s, 1 H), 1.59-1.13 (m, 4H), 1.07-0.80 (m, 7H), 0.72-0.59 (m, 3H); MS(ESI+) m/z 687.5 (M+H)+.
Sources & evidence
- ORD record
- ord-ae8b23ed3a3f459a8600e12abb80c23f
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09346795B2
Reaction notes
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