Sodium hydride → HCID 57937400, compound

HRID 1435546Notes

Reaction equation

HRID 1435546 reaction equation
[CH2:1]([NH:3][C:4]([C:6]1[CH:10]=[CH:9][NH:8][CH:7]=1)=[O:5])[CH3:2].[H-].[Na+].[F:13][C:14]([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)([F:16])[CH3:15].[NH4+].[Cl-]>C1COCC1.CCOC(C)=O>[F:13][C:14]([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:8]3[CH:9]=[CH:10][C:6]([C:4]([NH:3][CH2:1][CH3:2])=[O:5])=[CH:7]3)(=[O:34])=[O:35])=[CH:32][C:19]=2[N:18]=1)([F:16])[CH3:15]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 55284999N-ethyl-1H-pyrrole-3-carboxamideHCID 579373112-(1,1-difluoroethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazole-5-sulfonyl chloride

Product 1

HCID 57937400HCID 57937400, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

N-Ethyl-1H-pyrrole-3-carboxamide (50 mg, 0.36 mmol) was dissolved in THF (3 mL) and the solution was cooled down to 0° C. NaH (72 mg, 60%, 1.8 mmol) was then added and the reaction mixture was allowed to warm to room temperature and stirred for 1 hour at room temperature. The reaction mixture was cooled down to 0° C. again and 2-(1,1-difluoroethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazole-5-sulfonyl chloride (114 mg, 0.30 mmol) was added slowly, allowing the reaction to warm to room temperature and stirred for 3 hours. The reaction mixture was slowly added to a stirring mixture of EtOAc and NH4Cl at −20° C., which was extracted with EtOAc, washed with NH4Cl, water then brine. Concentrated under vacuum and purified by LCMS using high pH column 40-70% acetonitrile gradient to afford the title compound as a white solid. Yield: 25 mg (17%). 1H NMR (400 MHz, METHANOL-D4) δ 1.14 (t, J=7.23 Hz, 3 H), 1.32-1.41 (m, 2 H), 1.40-1.43 (m, 3 H), 1.43-1.53 (m, 2 H), 2.25 (t, J=19.53 Hz, 5H), 3.89 (dd, J=11.52, 2.54 Hz, 2 H), 4.37 (d, J=7.62 Hz, 2 H), 6.65 (s, 1 H), 7.31 (t, J=2.34 Hz, 1 H), 7.82 (s, 1 H), 7.88-7.94 (m, 1 H), 7.95-8.01 (m, 1 H), 8.40 (s, 1 H); MS (APPI) (M+H)+=481.2; Anal. Calc. for C22H26F2N4O4S+0.4 TFA: C, 52.05; H, 5.06; N, 10.65. Found: C, 52.41; H, 3.78; N, 10.41.

Workup

  1. temperatureto warm to room temperature
  2. temperatureThe reaction mixture was cooled down to 0° C. again
  3. customthe reaction
  4. temperatureto warm to room temperature
  5. stirringstirred for 3 hours
  6. extractionwhich was extracted with EtOAc
  7. washwashed with NH4Cl, water
  8. concentrationConcentrated under vacuum
  9. custompurified by LCMS

Sources & evidence

ORD record
ord-6b986a7cad5c44419e8af0218e2d57cb
Source dataset
uspto-grants-2009_11
Patent number
US07615642B2

Reaction notes

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