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

HRID 528862Notes

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](O)=[O:11])[C:6]=1[CH3:7].[CH3:44][C:45]1([CH3:55])[C:54]2[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=2)[CH2:48][NH:47][CH2:46]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:47]2[CH2:46][C:45]([CH3:55])([CH3:44])[C:54]3[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=3)[CH2:48]2)=[O:11])[N:4]=1)=[O:43])[CH2:40][CH2:41][CH3:42]

Participants

Reactant 2

HCID 1921721,2,3,4-Tetrahydro-4,4-dimethylisoquinoline

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

Product 1

HCID 71062419N,N-Dibutyl-4-chloro-1-(2-(4,4-dimethyl-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamideYield 35.7%

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 4,4-dimethyl-1,2,3,4-tetrahydroisoquinoline (Milestone Pharmtech, 9 mg, 0.056 mmol) were converted to the title compound (14 mg, 34%) following purification by preparative HPLC. 1H NMR (DMSO-d6, 1:1 mixture of amide rotamers) δ 8.64 (s, 1H), 8.20 (d, J=7.7 Hz, 1H), 8.14-7.90 (m, 5H), 7.78-7.59 (m, 3H), 7.36 (t, J=7.7 Hz, 1H), 7.26-7.13 (m, 2H), 7.11-7.02 (m, 0.5H), 6.99-6.89 (m, 0.5H), 4.85-4.20 (m, 2H), 3.58 (br s, 0.5H), 3.51-2.98 (m, 5H), 2.57-2.52 (m, 0.5H), 2.24 (s, 1.5H), 2.18 (s, 1.5H), 1.43-0.94 (m, 14H), 0.82 (t, J=7.3 Hz, 1H), 0.74 (t, J=7.3 Hz, 2H), 0.69 (t, J=7.4 Hz, 1.5H), 0.64 (t, J=7.4 Hz, 1.5H); MS(ESI+) m/z 768.3 (M+H)+.

Sources & evidence

ORD record: ord-7e93526e0d15401bbd9a1cfa8609dedb
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346795B2

Reaction notes

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