Sodium hydride → HCID 68682734, compound

HRID 2241536Notes

Reaction equation

HRID 2241536 reaction equation
[F:1][C:2]1([F:30])[CH2:7][CH2:6][N:5]([C:8]([C:10]2[NH:11][C:12]3[C:17]([CH:18]=2)=[CH:16][C:15]([C:19]([N:21]2[CH2:26][CH2:25][N:24]([CH:27]([CH3:29])[CH3:28])[CH2:23][CH2:22]2)=[O:20])=[CH:14][CH:13]=3)=[O:9])[CH2:4][CH2:3]1.[H-].[Na+].[CH:33]1([CH2:36]Br)[CH2:35][CH2:34]1.[Cl-].[NH4+]>CN(C)C=O>[CH:33]1([CH2:36][N:11]2[C:12]3[C:17](=[CH:16][C:15]([C:19]([N:21]4[CH2:22][CH2:23][N:24]([CH:27]([CH3:28])[CH3:29])[CH2:25][CH2:26]4)=[O:20])=[CH:14][CH:13]=3)[CH:18]=[C:10]2[C:8]([N:5]2[CH2:6][CH2:7][C:2]([F:1])([F:30])[CH2:3][CH2:4]2)=[O:9])[CH2:35][CH2:34]1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 81503BromomethylcyclopropaneHCID 68680853(4,4-Difluoro-piperidin-1-yl)-[5-(4-isopropyl-piperazine-1-carbonyl)-1H-indol-2-yl]-methanone

Product 1

HCID 68682734HCID 68682734, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

The suspension of 0.15 g (0.36 mmol) (4,4-difluoro-piperidin-1-yl)-[5-(4-isopropyl-piperazine-1-carbonyl)-1H-indol-2-yl]-methanone (example 32) and 17 mg (0.36 mmol; 55% dispersion in mineral oil) sodium hydride in 2 mL N,N-dimethylformamide was stirred for 30 min. at 70° C. Then, 42 μL (58 mg, 0.43 mmol) cyclopropylmethyl bromide were added and the solution was stirred another 45 min. at 70° C. After cooling to room temperature the reaction was poured on 10% aqueous ammonium chloride solution and the phases were separated. The aqueous phase was extracted three times with ethyl acetate. The combined organic layers were washed twice with water, followed by brine, dried over magnesium sulfate, filtered and evaporated. The crude product was purified by flash chromatography on silica gel with dichloromethane:methanol:ammonia (9:1:0.1 v/v) as eluant to give 0.16 g (97%) of the desired compound as a colorless foam.

Workup

  1. stirringthe solution was stirred another 45 min. at 70° C
  2. temperatureAfter cooling to room temperature the reaction
  3. customthe phases were separated
  4. extractionThe aqueous phase was extracted three times with ethyl acetate
  5. washThe combined organic layers were washed twice with water
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude product was purified by flash chromatography on silica gel with dichloromethane:methanol:ammonia (9:1:0.1 v/v) as eluant

Sources & evidence

ORD record
ord-0bf3185ba27a40c0b3affd09d982a4b8
Source dataset
uspto-grants-2010_05
Patent number
US07723325B2

Reaction notes

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