Sodium hydride → 1-{[2-(1,1-dimethylpropyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]sulfonyl}-N-methyl-1H-pyrrole-3-carboxamide

HRID 1435472Notes

Reaction equation

HRID 1435472 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[CH:9]=[CH:8][NH:7][CH:6]=1)=[O:4].[H-].[Na+].[CH3:12][C:13]([C:17]1[N:21]([CH2:22][CH:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[C:20]2[CH:29]=[CH:30][C:31]([S:33](Cl)(=[O:35])=[O:34])=[CH:32][C:19]=2[N:18]=1)([CH3:16])[CH2:14][CH3:15]>C1COCC1>[CH3:16][C:13]([C:17]1[N:21]([CH2:22][CH:23]2[CH2:24][CH2:25][O:26][CH2:27][CH2:28]2)[C:20]2[CH:29]=[CH:30][C:31]([S:33]([N:7]3[CH:8]=[CH:9][C:5]([C:3]([NH:2][CH3:1])=[O:4])=[CH:6]3)(=[O:35])=[O:34])=[CH:32][C:19]=2[N:18]=1)([CH3:12])[CH2:14][CH3:15]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 55284998N-methyl-1H-pyrrole-3-carboxamideHCID 579373072-tert-pentyl-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-benzo[d]imidazole-5-sulfonyl chloride

Product 1

HCID 236606631-{[2-(1,1-dimethylpropyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]sulfonyl}-N-methyl-1H-pyrrole-3-carboxamideYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Following the same procedure in Example 29, using N-methyl-1H-pyrrole-3-carboxamide (57 mg, 0.46 mmol) (see following step B for preparation), sodium hydride (110 mg, 60%, 2.76 mmol), 2-(1,1-dimethylpropyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazole-5-sulfonyl chloride (352 mg, 0.92 mmol) in THF (10 mL). The crude product was purified by MPLC using EtOAc on silica gel to give 134 mg (62%) of a white solid as the title compound. 1H NMR (400 MHz, METHANOL-D4) δ 0.77 (t, J=7.42 Hz, 3 H), 1.40-1.56 (m, 4 H), 1.59 (s, 6 H), 1.94 (q, J=7.42 Hz, 2 H), 2.19-2.37 (m, 1 H), 2.79 (s, 3 H), 3.24-3.36 (m, 2 H), 3.84-3.94 (m, 2 H), 4.41 (d, J=7.62 Hz, 2 H), 6.63 (dd, J=3.32, 1.56 Hz, 1 H), 7.29 (dd, J=3.32, 2.34 Hz, 1 H), 7.78 (dd, J=2.15, 1.76 Hz, 1 H), 7.88-7.92 (m, 1 H), 7.92-7.98 (m, 1 H), 8.26 (dd, J=1.56, 0.59 Hz, 1 H); MS (ESI) (M+H)+=473.0; Anal. Calcd for C24H32N4O4S+1.0 TFA (586.63): C, 53.23; H, 5.67; N, 9.55. Found: C, 53.28; H, 5.77; N, 9.42.

Workup

  1. customThe crude product was purified by MPLC

Sources & evidence

ORD record
ord-e3c593855fa7412381f8d118fd7d4ce1
Source dataset
uspto-grants-2009_11
Patent number
US07615642B2

Reaction notes

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