Ethyl 4-fluoro-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate → Ethyl 4-(4-chloro-3-(dibutylcarbamoyl)-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate

HRID 528926Notes

Reaction equation

HRID 528926 reaction equation
[CH2:1]([N:5]([CH2:14][CH2:15][CH2:16][CH3:17])[C:6]([C:8]1[C:12]([Cl:13])=[CH:11][NH:10][N:9]=1)=[O:7])[CH2:2][CH2:3][CH3:4].F[C:19]1[CH:29]=[CH:28][C:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:21][C:20]=1[C:30]([N:32]1[CH2:41][CH2:40][C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH2:33]1)=[O:31]>>[Cl:13][C:12]1[C:8]([C:6](=[O:7])[N:5]([CH2:14][CH2:15][CH2:16][CH3:17])[CH2:1][CH2:2][CH2:3][CH3:4])=[N:9][N:10]([C:19]2[CH:29]=[CH:28][C:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:21][C:20]=2[C:30]([N:32]2[CH2:41][CH2:40][C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[CH2:33]2)=[O:31])[CH:11]=1

Participants

3

Reactant 2

HCID 71061015Ethyl 4-fluoro-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate2×HCID 178449066HCID 178449066, compound

Product 1

HCID 71062365Ethyl 4-(4-chloro-3-(dibutylcarbamoyl)-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoateYield 71%

Procedure

Following a procedure analogous to that for the synthesis of Intermediate 1E, N,N-dibutyl-4-chloro-1H-pyrazole-3-carboxamide (100 mg, 0.39 mmol) and ethyl 4-fluoro-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate (Intermediate 1D, 140 mg, 0.43 mmol) were converted to the title compound (156 mg, 71%). 1H NMR (CDCl3, mixture of amide rotamers) δ 8.23-8.16 (m, 1H), 8.12-8.06 (m, 1H), 7.98-7.85 (m, 1H), 7.71-7.58 (m, 1H), 7.26-7.04 (m, 3.5H), 6.78 (d, J=7.5 Hz, 0.5H), 4.99-4.70 (m, 1H), 4.45-4.24 (m, 2.5H), 4.17-4.01 (m, 1H), 3.79-3.73 (m, 0.5H), 3.57-3.15 (m, 5H), 3.11-2.87 (m, 1H), 2.74 (t, J=5.8 Hz, 1H), 1.67-1.06 (m, 10.5H), 1.00-0.86 (m, 3.5H), 0.86-0.73 (m, 3H); MS(ESI+) m/z 565.3 (M+H)+.

Sources & evidence

ORD record
ord-a80e6fdb2a324b718256737f894ae83d
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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