Sodium hydride → [1-Cyclopropylmethyl-5-(4-isopropyl-piperazine-1-carbonyl)-1H-indol-2-yl]-[4-(piperidine-1-sulfonyl)-piperazin-1-yl]-methanone

HRID 1992455Notes

Reaction equation

HRID 1992455 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[NH:17][C:16]([C:21]([N:23]2[CH2:28][CH2:27][N:26]([S:29]([N:32]4[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]4)(=[O:31])=[O:30])[CH2:25][CH2:24]2)=[O:22])=[CH:15]3)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].[H-].[Na+].[CH:40]1([CH2:43]Br)[CH2:42][CH2:41]1.[Cl-].[NH4+]>CN(C)C=O>[CH:40]1([CH2:43][N:17]2[C:18]3[C:14](=[CH:13][C:12]([C:10]([N:7]4[CH2:8][CH2:9][N:4]([CH:1]([CH3:3])[CH3:2])[CH2:5][CH2:6]4)=[O:11])=[CH:20][CH:19]=3)[CH:15]=[C:16]2[C:21]([N:23]2[CH2:28][CH2:27][N:26]([S:29]([N:32]3[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]3)(=[O:31])=[O:30])[CH2:25][CH2:24]2)=[O:22])[CH2:42][CH2:41]1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 81503BromomethylcyclopropaneHCID 68536516[5-(4-Isopropyl-piperazine-1-carbonyl)-1H-indol-2-yl]-[4-(piperidine-1-sulfonyl)-piperazin-1-yl]-methanone

Product 1

HCID 68539297[1-Cyclopropylmethyl-5-(4-isopropyl-piperazine-1-carbonyl)-1H-indol-2-yl]-[4-(piperidine-1-sulfonyl)-piperazin-1-yl]-methanoneYield 91.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A suspension of 0.15 g (0.28 mmol) [5-(4-isopropyl-piperazine-1-carbonyl)-1H-indol-2-yl]-[4-(piperidine-1-sulfonyl)-piperazin-1-yl]-methanone (example 2) and 14 mg (0.32 mmol; 55% dispersion in mineral oil) sodium hydride in 2 mL N,N-dimethyl-formamide was stirred 20 min. at 70° C. 34 μL (48 mg, 0.35 mmol) cyclopropylmethyl bromide were added and the solution was stirred another 45 min. at 70° C. After cooling to room temperature, the mixture was poured into 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 three times with water, brine, dried over magnesium sulfate, filtered and evaporated. The crude product was purified by flash chromatography on silica gel with dichloromethane:methanol (9:1 v/v) as eluant to give 0.15 g (91%) of the desired compound as colorless foam. MS (ISP): 585.3 (M+H)+.

Workup

  1. stirringthe solution was stirred another 45 min. at 70° C
  2. temperatureAfter cooling to room temperature
  3. customthe phases were separated
  4. extractionThe aqueous phase was extracted three times with ethyl acetate
  5. washThe combined organic layers were washed three times with water, brine
  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 (9:1 v/v) as eluant

Sources & evidence

ORD record
ord-030b5dea2c0349da87b4c2f9879382fd
Source dataset
uspto-grants-2010_01
Patent number
US07648979B2

Reaction notes

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