4-Fluorobenzenesulfonyl chloride → (4,4-difluoropiperidin-1-yl)(1-(4-fluorophenylsulfonyl)-5-(1-isopropylpiperidin-4-yloxy)-1H-indol-2-yl)methanone

HRID 19842

Reaction equation

HRID 19842 reaction equation
[H-].[Na+].[F:3][C:4]1([F:31])[CH2:9][CH2:8][N:7]([C:10]([C:12]2[NH:13][C:14]3[C:19]([CH:20]=2)=[CH:18][C:17]([O:21][CH:22]2[CH2:27][CH2:26][N:25]([CH:28]([CH3:30])[CH3:29])[CH2:24][CH2:23]2)=[CH:16][CH:15]=3)=[O:11])[CH2:6][CH2:5]1.[F:32][C:33]1[CH:38]=[CH:37][C:36]([S:39](Cl)(=[O:41])=[O:40])=[CH:35][CH:34]=1>CN(C)C=O>[F:31][C:4]1([F:3])[CH2:9][CH2:8][N:7]([C:10]([C:12]2[N:13]([S:39]([C:36]3[CH:37]=[CH:38][C:33]([F:32])=[CH:34][CH:35]=3)(=[O:41])=[O:40])[C:14]3[C:19]([CH:20]=2)=[CH:18][C:17]([O:21][CH:22]2[CH2:27][CH2:26][N:25]([CH:28]([CH3:29])[CH3:30])[CH2:24][CH2:23]2)=[CH:16][CH:15]=3)=[O:11])[CH2:6][CH2:5]1

Participants

5

Reactant 3

HCID 95884-Fluorobenzenesulfonyl chlorideHCID 24758Sodium hydrideHCID 11603838(4,4-Difluoropiperidin-1-yl)[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]methanone2×

Product 1

HCID 16739387(4,4-difluoropiperidin-1-yl)(1-(4-fluorophenylsulfonyl)-5-(1-isopropylpiperidin-4-yloxy)-1H-indol-2-yl)methanoneYield 60.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

Sodium hydride (60% dispersion in oil, 24 mg, 1.1 eq.) was added to a mixture of (4,4-difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone (intermediate 1, 200 mg, 1.0 eq.) in N,N-dimethylformamide (2 mL) and stirred at 70° C. for 30 min. 4-Fluorobenzenesulfonyl chloride (115 mg, 1.2 eq.) was added and the reaction mixture was stirred at 70° C. overnight. The reaction mixture was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate and the combined organic fractions were washed with water and brine, dried over sodium sulfate, filtered, evaporated to dryness and purified on silica gel, eluting with dichloromethane/methanol 49:1 to yield 167 mg (60%) of the desired product as yellow foam. MS (m/e): 564.4 (MH+, 100%).

Workup

  1. stirringthe reaction mixture was stirred at 70° C. overnight
  2. customThe reaction mixture was partitioned between ethyl acetate and water
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. washthe combined organic fractions were washed with water and brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated to dryness
  8. custompurified on silica gel
  9. washeluting with dichloromethane/methanol 49:1

Sources & evidence

ORD record
ord-d19d1de50ed84a7a86192d66ab48a4da
Source dataset
uspto-grants-2010_06
Patent number
US07745479B2

Linked notes

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