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

HRID 528861Notes

Reaction equation

HRID 528861 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].[CH3:44][CH:45]1[C:54]2[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=2)[CH2:48][CH2:47][NH:46]1>>[CH2:39]([N:34]([CH2:35][CH2:36][CH2:37][CH3:38])[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:46]2[CH2:47][CH2:48][C:49]3[C:54](=[CH:53][CH:52]=[CH:51][CH:50]=3)[CH:45]2[CH3:44])=[O:12])[N:4]=1)=[O:43])[CH2:40][CH2:41][CH3:42]

Participants

3

Reactant 2

HCID 922141-Methyl-1,2,3,4-tetrahydroisoquinolineHCID 710621452-(4-Chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-5-(naphthalen-2-ylsulfonylcarbamoyl)benzoic acid2×

Product 1

HCID 70690005N,N-Dibutyl-4-chloro-5-methyl-1-(2-(1-methyl-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-1H-pyrazole-3-carboxamideYield 31.2%

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, 32 mg, 0.051 mmol) and 1-methyl-1,2,3,4-tetrahydroisoquinoline (Parkway Scientific, 8 mg, 0.056 mmol) were converted to the title compound (12 mg, 31%) following purification by preparative HPLC. 1H NMR (DMSO-d6, mixture of amide rotamers) δ 8.65 (s, 1H), 8.21 (d, J=8.1 Hz, 2H), 8.16-8.03 (m, 4H), 8.01-7.94 (m, 1.5H), 7.91 (br s, 0.5H), 7.77-7.61 (m, 3H), 7.27-6.93 (m, 2H), 5.48-5.31 (m, 0.5H), 3.68-3.55 (m, 1H), 3.17-2.57 (m, 4.5H), 2.55 (t, J=5.5 Hz, 3H), 2.20 (s, 3H), 1.53-1.36 (3.5H), 1.29-1.23 (m, 2.5H), 1.21-1.12 (m, 4H), 0.95-0.82 (m, 3.5H), 0.66 (d, J=7.3 Hz, 3H), 0.56 (br s, 0.5H); MS(ESI+) m/z 754.3 (M+H)+.

Sources & evidence

ORD record
ord-fd1ef4a53deb4ae499694155071e8b59
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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