Ethyl 4-fluoro-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate → Ethyl 4-(4-chloro-3-(dibutylamino)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate
Reaction equation
[CH2:1]([N:5]([CH2:13][CH2:14][CH2:15][CH3:16])[C:6]1[C:10]([Cl:11])=[C:9]([CH3:12])[NH:8][N:7]=1)[CH2:2][CH2:3][CH3:4].F[C:18]1[CH:28]=[CH:27][C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:20][C:19]=1[C:29]([N:31]1[CH2:40][CH2:39][C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH2:32]1)=[O:30]>>[Cl:11][C:10]1[C:6]([N:5]([CH2:13][CH2:14][CH2:15][CH3:16])[CH2:1][CH2:2][CH2:3][CH3:4])=[N:7][N:8]([C:18]2[CH:28]=[CH:27][C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:20][C:19]=2[C:29]([N:31]2[CH2:40][CH2:39][C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[CH2:32]2)=[O:30])[C:9]=1[CH3:12]Participants
Procedure
Following a procedure analogous to that for the synthesis of Intermediate 1E, N,N-dibutyl-4-chloro-5-methyl-1H-pyrazol-3-amine (160 mg, 0.66 mmol) and ethyl 4-fluoro-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate (Intermediate 1D, 258 mg, 0.79 mmol) were converted to the title compound (98 mg, 27%). 1H NMR (CDCl3, 2:1 mixture of amide rotamers) δ 8.19 (d, J=8.1 Hz, 1H), 8.12 (d, J=1.7 Hz, 1H), 7.40 (d, J=8.33 Hz, 1H), 7.08-7.30 (m, 3.5H), 6.92 (d, J=7.5 Hz, 0.5H), 4.95 (d, J=17.1 Hz., 0.5H), 4.68 (d, J=17.10 Hz, 0.5H), 4.31-4.53 (m, 2.5H), 4.12 (d, J=4.1 Hz, 0.5H), 3.51-3.76 (m, 1.5H), 3.03-3.36 (m, 4.5H), 2.75-3.03 (m, 2H), 2.58 (s, 2H), 2.47 (s, 1H), 1.33-1.51 (m, 7H), 1.13-1.30 (m, 4H), 0.77-0.96 (m, 6H); MS(ESI+) m/z 551.4 (M+H)+.
Sources & evidence
- ORD record
- ord-53924e1bcb1a4272a9a53d85413dd90f
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09346795B2
Reaction notes
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