Sodium hydride → 1-{[2-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]sulfonyl}-N-cyclopropyl-1H-pyrazole-4-carboxamide

HRID 1435437Notes

Reaction equation

HRID 1435437 reaction equation
[H-].[Na+].[CH:3]1([NH:6][C:7]([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)=[O:8])[CH2:5][CH2:4]1.[C:14]([C:18]1[N:22]([CH2:23][CH:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[C:21]2[CH:30]=[CH:31][C:32]([S:34](Cl)(=[O:36])=[O:35])=[CH:33][C:20]=2[N:19]=1)([CH3:17])([CH3:16])[CH3:15]>C1COCC1.CN(C=O)C>[C:14]([C:18]1[N:22]([CH2:23][CH:24]2[CH2:25][CH2:26][O:27][CH2:28][CH2:29]2)[C:21]2[CH:30]=[CH:31][C:32]([S:34]([N:11]3[CH:10]=[C:9]([C:7]([NH:6][CH:3]4[CH2:4][CH2:5]4)=[O:8])[CH:13]=[N:12]3)(=[O:35])=[O:36])=[CH:33][C:20]=2[N:19]=1)([CH3:17])([CH3:15])[CH3:16]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 20785111HCID 20785111, compoundHCID 579372982-tert-Butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazole-5-sulfonyl chloride

Product 1

HCID 236601091-{[2-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]sulfonyl}-N-cyclopropyl-1H-pyrazole-4-carboxamideYield 33%

Reagents, catalysts & solvents 1

HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (0.98 g, 60%, 25 mmol) was added to a solution of N-cyclopropyl-1H-pyrazole-4-carboxamide (0.49 g, 3.5 mmol) (see following steps B and C for preparation) in 40 mL of THF-DMF (3:1) at 0° C. Stirring for 1 h at 0° C. and 0.5 h at room temperature, 2-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazole-5-sulfonyl chloride (1.30 g, 3.5 mmol) was added. The reaction mixture was stirred for 2 h at 0° C., quenched with NaHCO3 (10 mL) and extracted with EtOAc (3×50 mL). The combined organic phases were washed with NaCl (20 mL) and dried over Na2SO4. The crude product was purified by MPLC using Hex/EtOAc (1:2) on silica gel to give 0.54 g (33%) of a white solid as the title compound. 1H NMR (400 MHz, METHANOL-D4) δ 0.52-0.59 (m, 2 H), 0.71-0.79 (m, 2 H), 1.39-1.57 (m, 4 H), 1.60 (s, 9 H), 2.22-2.37 (m, 1 H), 2.71-2.79 (m, 1 H), 3.26-3.34 (m, 2 H), 3.86-3.93 (m, 2 H), 4.43 (d, J=7.62 Hz, 2 H), 7.91-7.95 (m, 1 H), 7.97-8.01 (m, 1 H), 8.03 (d, J=0.78 Hz, 1 H), 8.34 (d, J=1.37 Hz, 1 H), 8.74 (d, J=0.59 Hz, 1 H); MS (ESI) (M+H)+=485.8.

Workup

  1. stirringThe reaction mixture was stirred for 2 h at 0° C.
  2. customquenched with NaHCO3 (10 mL)
  3. extractionextracted with EtOAc (3×50 mL)
  4. washThe combined organic phases were washed with NaCl (20 mL)
  5. dry with materialdried over Na2SO4
  6. customThe crude product was purified by MPLC

Sources & evidence

ORD record
ord-dcd6431f96c7480da5f2b1fd717f0d4b
Source dataset
uspto-grants-2009_11
Patent number
US07615642B2

Reaction notes

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