Pyrrole → 2-tert-Butyl-5-(1H-pyrrol-1-ylsulfonyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazole

HRID 1435439Notes

Reaction equation

HRID 1435439 reaction equation
[H-].[Na+].[NH:3]1[CH:7]=[CH:6][CH:5]=[CH:4]1.[C:8]([C:12]1[N:16]([CH2:17][CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[C:15]2[CH:24]=[CH:25][C:26]([S:28](Cl)(=[O:30])=[O:29])=[CH:27][C:14]=2[N:13]=1)([CH3:11])([CH3:10])[CH3:9]>C1COCC1>[C:8]([C:12]1[N:16]([CH2:17][CH:18]2[CH2:19][CH2:20][O:21][CH2:22][CH2:23]2)[C:15]2[CH:24]=[CH:25][C:26]([S:28]([N:3]3[CH:7]=[CH:6][CH:5]=[CH:4]3)(=[O:29])=[O:30])=[CH:27][C:14]=2[N:13]=1)([CH3:11])([CH3:9])[CH3:10]

Participants

5

Reactant 3

HCID 8027PyrroleHCID 24758Sodium hydrideHCID 579372982-tert-Butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazole-5-sulfonyl chloride

Product 1

HCID 236601102-tert-Butyl-5-(1H-pyrrol-1-ylsulfonyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazoleYield 35%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (139 mg, 60%, 3.5 mmol) was added to a solution of pyrrole (200 uL, 194 mg, 2.9 mmol) in THF (10 mL). Stirring for 3 h at room temperature, 2-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazole-5-sulfonyl chloride (185 mg, 0.5 mmol) was added. The reaction mixture was stirred overnight at room temperature, quenched with NH4Cl (5 mL), diluted with EtOAc (50 mL), washed with NaCl (2×20 mL) and dried over Na2SO4. The crude product was purified by MPLC using Hex/EtOAc (1:1) on silica gel to give 70 mg (35%) of a white solid as the title compound. 1H NMR (400 MHz, METHANOL-D4) δ 1.36-1.53 (m, 4 H), 1.55 (s, 9 H), 2.18-2.38 (m, 1 H), 3.22-3.35 (m, 2 H), 3.88 (m, 2 H), 4.33 (d, J=7.42 Hz, 2 H), 6.22-6.31 (m, 2 H), 7.13-7.29 (m, 2 H), 7.71 (d, J=8.8 Hz, 1 H), 7.77 (dd, J=8.6, 1.8 Hz, 1 H), 8.13 (d, J=1.37 Hz, 1 H); MS (ESI) (M+H)+=401.8; Anal. Calcd for C21H27N3O3S+0.30H2O (406.94): C, 61.98; H, 6.84; N, 10.33. Found: C, 62.10; H, 6.90; N, 10.43.

Workup

  1. stirringThe reaction mixture was stirred overnight at room temperature
  2. customquenched with NH4Cl (5 mL)
  3. additiondiluted with EtOAc (50 mL)
  4. washwashed with NaCl (2×20 mL)
  5. dry with materialdried over Na2SO4
  6. customThe crude product was purified by MPLC

Sources & evidence

ORD record
ord-37012739f8a7411ea2cbdc1281081b5b
Source dataset
uspto-grants-2009_11
Patent number
US07615642B2

Reaction notes

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