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

HRID 1435548Notes

Reaction equation

HRID 1435548 reaction equation
[H-].[Na+].[NH:3]1[CH:7]=[CH:6][C:5]([CH:8]=[O:9])=[CH:4]1.[F:10][C:11]([C:14]1[N:18]([CH2:19][CH:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[C:17]2[CH:26]=[CH:27][C:28]([S:30](Cl)(=[O:32])=[O:31])=[CH:29][C:16]=2[N:15]=1)([F:13])[CH3:12]>C1COCC1>[F:10][C:11]([C:14]1[N:18]([CH2:19][CH:20]2[CH2:21][CH2:22][O:23][CH2:24][CH2:25]2)[C:17]2[CH:26]=[CH:27][C:28]([S:30]([N:3]3[CH:7]=[CH:6][C:5]([CH:8]=[O:9])=[CH:4]3)(=[O:31])=[O:32])=[CH:29][C:16]=2[N:15]=1)([F:13])[CH3:12]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 6403081H-pyrrole-3-carboxaldehydeHCID 579373112-(1,1-difluoroethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazole-5-sulfonyl chloride

Product 1

HCID 579373571-{[2-(1,1-difluoroethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]sulfonyl}-1H-pyrrole-3-carbaldehyde

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (0.55 mg, 60%, 13.8 mmol) was added to a solution of 1H-Pyrrole-3-carbaldehyde (0.26 g, 2.7 mmol) in 30 mL of THF at 0° C. After stirring for 1 h, 2-(1,1-difluoroethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazole-5-sulfonyl chloride (0.95 g, 2.5 mmol) was added. The reaction mixture was stirred for 3 h at 0° C., quenched with NaHCO3 (10 mL) and diluted with EtOAc (150 mL). The organic phases were washed with NaCl (2×20 mL) and dried over Na2SO4. The product was purified by normal-phase MPLC using Hex/EtOAc (1:1) to provide the title compound as a white solid. Yield: 0.86 g (79%); MS (ESI) (M+H)+=437.88.

Workup

  1. stirringThe reaction mixture was stirred for 3 h at 0° C.
  2. customquenched with NaHCO3 (10 mL)
  3. additiondiluted with EtOAc (150 mL)
  4. washThe organic phases were washed with NaCl (2×20 mL)
  5. dry with materialdried over Na2SO4
  6. customThe product was purified by normal-phase

Sources & evidence

ORD record
ord-55128fb9775f45aeaf5a0b1e3119af1e
Source dataset
uspto-grants-2009_11
Patent number
US07615642B2

Reaction notes

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