7-(Trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline → N,N-Dibutyl-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(7-(trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide

HRID 528863Notes

Reaction equation

[Cl:1][C:2]1[C:3]([C:33](=[O:43])[N:34]([CH2:39][CH2:40][CH2:41][CH3:42])[CH2:35][CH2:36][CH2:37][CH3:38])=[N:4][N:5]([C:8]2[CH:16]=[CH:15][C:14]([C:17](=[O:32])[NH:18][S:19]([C:22]3[CH:31]=[CH:30][C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH:23]=3)(=[O:21])=[O:20])=[CH:13][C:9]=2[C:10]([OH:12])=O)[C:6]=1[CH3:7].[F:44][C:45]([F:57])([F:56])[C:46]1[CH:55]=[C:54]2[C:49]([CH2:50][CH2:51][NH:52][CH2:53]2)=[CH:48][CH:47]=1>>[CH2:35]([N:34]([CH2:39][CH2:40][CH2:41][CH3:42])[C:33]([C:3]1[C:2]([Cl:1])=[C:6]([CH3:7])[N:5]([C:8]2[CH:16]=[CH:15][C:14]([C:17](=[O:32])[NH:18][S:19]([C:22]3[CH:31]=[CH:30][C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH:23]=3)(=[O:20])=[O:21])=[CH:13][C:9]=2[C:10]([N:52]2[CH2:51][CH2:50][C:49]3[C:54](=[CH:55][C:46]([C:45]([F:44])([F:57])[F:56])=[CH:47][CH:48]=3)[CH2:53]2)=[O:12])[N:4]=1)=[O:43])[CH2:36][CH2:37][CH3:38]

Participants

Reactant 2

HCID 103755517-(Trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline

HCID 710621452-(4-Chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-5-(naphthalen-2-ylsulfonylcarbamoyl)benzoic acid2×

Product 1

HCID 71062206N,N-Dibutyl-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(7-(trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamideYield 72.8%

Procedure

Following a procedure analogous to that for the synthesis of Intermediate 93B, 2-(4-chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-5-(naphthalen-2-ylsulfonylcarbamoyl)benzoic acid (Intermediate 91F, 21 mg, 0.034 mmol) and 7-(trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline (7 mg, 0.037 mmol) were converted to the title compound (20 mg, 71%) following purification by preparative HPLC. 1H NMR (1:1 CD3OD:CDCl3, 1.5:1 mixture of amide rotamers) δ 8.69-8.58 (m, 1H), 8.19-8.13 (m, 1H), 8.08-8.02 (m, 2H), 8.01-7.97 (m, 1H), 7.95-7.91 (m, 1H), 7.90-7.86 (m, 1H), 7.60-7.54 (m, 2H), 7.45-7.34 (m, 2.5H), 7.28-7.23 (m, 1H), 7.17-7.14 (m, 0.5H), 4.89-4.64 (m, 1.5H), 4.52 (s, 1H), 4.16-4.02 (m, 0.5H), 3.70-3.34 (m, 2.5H), 3.24-2.75 (m, 4.5H), 2.28 (s, 2H), 2.23 (s, 1H), 1.51-0.93 (m, 8H), 0.87 (dt, J=17.8, 7.4 Hz, 3H), 0.75 (t, J=7.4 Hz, 2H), 0.64 (t, J=7.4 Hz, 1H); MS(ESI+) m/z 808.3 (M+H)+.

Sources & evidence

ORD record: ord-cf70775c7a0d426fbd4831f7c118d91a
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346795B2

Reaction notes

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