4-(4-(dibutylcarbamoyl)-1-methyl-1H-imidazol-5-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoic acid → N,N-Dibutyl-5-(4-(8-chloronaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1-methyl-1H-imidazole-4-carboxamide

HRID 529032Notes

Reaction equation

[CH2:1]([N:5]([CH2:35][CH2:36][CH2:37][CH3:38])[C:6]([C:8]1[N:9]=[CH:10][N:11]([CH3:34])[C:12]=1[C:13]1[CH:21]=[CH:20][C:16]([C:17](O)=[O:18])=[CH:15][C:14]=1[C:22]([N:24]1[CH2:33][CH2:32][C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH2:25]1)=[O:23])=[O:7])[CH2:2][CH2:3][CH3:4].Cl[C:40]1[CH:49]=[CH:48][C:47]([Cl:50])=[C:46]2[C:41]=1[CH:42]=[CH:43][C:44]([S:51]([NH2:54])(=[O:53])=[O:52])=[CH:45]2>>[CH2:1]([N:5]([CH2:35][CH2:36][CH2:37][CH3:38])[C:6]([C:8]1[N:9]=[CH:10][N:11]([CH3:34])[C:12]=1[C:13]1[CH:21]=[CH:20][C:16]([C:17](=[O:18])[NH:54][S:51]([C:44]2[CH:43]=[CH:42][C:41]3[C:46](=[C:47]([Cl:50])[CH:48]=[CH:49][CH:40]=3)[CH:45]=2)(=[O:53])=[O:52])=[CH:15][C:14]=1[C:22]([N:24]1[CH2:33][CH2:32][C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH2:25]1)=[O:23])=[O:7])[CH2:2][CH2:3][CH3:4]

Participants

Reactant 2

HCID 710622164-(4-(dibutylcarbamoyl)-1-methyl-1H-imidazol-5-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoic acid

HCID 710625565,8-Dichloronaphthalene-2-sulfonamide2×

Product 1

HCID 86718949N,N-Dibutyl-5-(4-(8-chloronaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1-methyl-1H-imidazole-4-carboxamideYield 12.1%

Procedure

Following a procedure analogous to that for the synthesis of Example 265, 4-(4-(dibutylcarbamoyl)-1-methyl-1H-imidazol-5-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoic acid (150 mg, 0.29 mmol) and 8-chloronaphthalene-2-sulfonamide (Intermediate 5, 140 mg, 0.58 mmol) were converted to the title compound (26 mg, 12%). 1H NMR (CD3OD, 1:1 mixture of amide rotamers) δ 8.99 (s, 1H), 8.18-8.09 (m, 3H), 8.05 (dd, J=8.4, 2.0 Hz, 1H), 7.94-7.91 (m, 1H), 7.72 (dd, J=7.2, 1.2 Hz, 1H), 7.69 (s, 0.5H), 7.62-7.55 (m, 1.5H), 7.42 (dd, J=8.0, 4.8 Hz, 1H), 7.21-7.13 (m, 3.5H), 6.93 (d, J=8.0 Hz, 0.5H), 4.78 (br s, 0.5H), 4.62-4.49 (m, 1.5H), 3.90 (br s, 0.5H), 3.60 (br s, 0.5H), 3.50 (s, 3H), 3.49-3.39 (m, 2H), 3.24 (t, J=6.4 Hz, 0.5H), 3.18-3.13 (m, 1.5H), 2.90 (br s, 1.5H), 2.85-2.65 (m, 2.5H), 1.50-1.09 (m, 8H), 0.89-0.79 (m, 6H); MS(ESI+) m/z 742.2 (M+H)+.

Sources & evidence

ORD record: ord-84a7a6c3d48243c6b41fcdac0b0128ad
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346795B2

Reaction notes

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