4-(4-Chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoic acid → N,N-Dibutyl-1-(4-(7-(2-(tert-butyldimethylsilyloxy)ethoxy)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-4-chloro-5-methyl-1H-pyrazole-3-carboxamide

HRID 528817Notes

Reaction equation

HRID 528817 reaction equation
[Cl:1][C:2]1[C:3]([C:29](=[O:39])[N:30]([CH2:35][CH2:36][CH2:37][CH3:38])[CH2:31][CH2:32][CH2:33][CH3:34])=[N:4][N:5]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][C:9]=2[C:17]([N:19]2[CH2:28][CH2:27][C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH2:20]2)=[O:18])[C:6]=1[CH3:7].[Si:40]([O:47][CH2:48][CH2:49][O:50][C:51]1[CH:60]=[C:59]2[C:54]([CH:55]=[CH:56][C:57]([S:61]([NH2:64])(=[O:63])=[O:62])=[CH:58]2)=[CH:53][CH:52]=1)([C:43]([CH3:46])([CH3:45])[CH3:44])([CH3:42])[CH3:41]>>[CH2:35]([N:30]([CH2:31][CH2:32][CH2:33][CH3:34])[C:29]([C:3]1[C:2]([Cl:1])=[C:6]([CH3:7])[N:5]([C:8]2[CH:16]=[CH:15][C:11]([C:12](=[O:14])[NH:64][S:61]([C:57]3[CH:56]=[CH:55][C:54]4[C:59](=[CH:60][C:51]([O:50][CH2:49][CH2:48][O:47][Si:40]([C:43]([CH3:46])([CH3:45])[CH3:44])([CH3:41])[CH3:42])=[CH:52][CH:53]=4)[CH:58]=3)(=[O:63])=[O:62])=[CH:10][C:9]=2[C:17]([N:19]2[CH2:28][CH2:27][C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH2:20]2)=[O:18])[N:4]=1)=[O:39])[CH2:36][CH2:37][CH3:38]

Participants

3

Reactant 2

HCID 710621944-(4-Chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoic acid2×HCID 710623897-(2-(tert-Butyldimethylsilyloxy)ethoxy)naphthalene-2-sulfonamide2×

Product 1

HCID 86718881N,N-Dibutyl-1-(4-(7-(2-(tert-butyldimethylsilyloxy)ethoxy)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-4-chloro-5-methyl-1H-pyrazole-3-carboxamideYield 47%

Procedure

Following a procedure analogous to that for the synthesis of Example 1,4-(4-chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoic acid (Intermediate 1F, 40 mg, 0.073 mmol) and 7-(2-(tert-butyldimethylsilyloxy)ethoxy)naphthalene-2-sulfonamide (Intermediate 50B, 33 mg, 0.087 mmol) were converted to the title compound (31 mg, 47%) after purification using flash column chromatography (gradient from 0% to 3% MeOH/CH2Cl2). 1H NMR (CDCl3, 2:1 mixture of amide rotamers) δ 8.62 (s, 1H), 8.11-8.09 (m, 1H), 7.97-7.96 (m, 1H), 7.89-7.88 (m, 2H), 7.84 (d, J=8.9 Hz, 1H), 7.55-7.52 (m, 1H), 7.40-7.38 (m, 2H), 7.23-7.07 (m, 3.5H), 6.85 (d, J=7.4 Hz, 0.5H), 4.75 (br s, 1H), 4.63 (br s, 1H), 4.42 (s, 1H), 4.27-4.24 (m, 2H), 3.85-3.81 (m, 2H), 3.46 (br s, 2H), 3.18-3.15 (m, 2H), 3.02 (br s, 1.5H), 2.84 (br s, 1.5H), 2.29 (s, 2H), 2.24 (s, 1H), 1.50-1.45 (m, 1H), 1.41-1.36 (m, 1H), 1.32-1.20 (m, 6H), 1.12-0.99 (m, 1H), 0.93-0.86 (m, 12H), 0.74 (t, J=7.4 Hz, 2H), 0.68 (t, J=7.2 Hz, 1H), 0.10 (s, 6H); MS(ESI+) m/z 914.3 (M+H)+.

Sources & evidence

ORD record
ord-54e5fd7d118046f2900c7137f28f68da
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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