Water → HCID 178439461, compound

HRID 1924298Notes

Reaction equation

HRID 1924298 reaction equation
F[C:2]1[CH:3]=C2[C:8](=[CH:9][CH:10]=1)[NH:7]C=C2.[H-].[Na+].Cl[CH2:14][N:15]1[CH2:19][CH:18]([CH2:20][CH2:21][CH3:22])[CH2:17][C:16]1=[O:23].[OH2:24].C[N:26]([CH:28]=O)[CH3:27]>>[O-:24][N+:26]1[CH:28]=[CH:3][CH:2]=[C:10]2[C:9]([CH2:14][N:15]3[CH2:19][CH:18]([CH2:20][CH2:21][CH3:22])[CH2:17][C:16]3=[O:23])=[CH:8][NH:7][C:27]=12

Participants

6

Reactant 5

HCID 962WaterHCID 6228Dimethylformamide2×HCID 24758Sodium hydrideHCID 678615-FluoroindoleHCID 536292161-(Chloromethyl)-4-propylpyrrolidin-2-one

Product 1

HCID 178439461HCID 178439461, compoundYield 33%

Procedure

To a solution of 5-fluoroindole x157 (405 mg, 3 mmol, 1 eq) of in DMF (7 ml) maintained under argon is added NaH (60% in mineral oil; 120 mg, 3 mmol, 1 eq). The resulting mixture is stirred for three hours at room temperature, then a solution of 1-(chloromethyl)-4-propylpyrrolidin-2-one x63 in DMF (1 M, 3 ml, 3 mmol, 1 eq) is added. The reaction mixture is stirred for 20 hours at room temperature. Water (70 ml) is added and the resulting mixture is extracted with ethyl acetate (30 ml). The organic phase is washed twice with water and dried over Na2SO4. After filtration and evaporation of volatiles, the crude product is purified by two consecutive chromatographies on silicagel (CH2Cl2/MeOH gradient, then CH2Cl2). Pure 1-[(7-oxido-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl]-4-propylpyrrolidin-2-one 278 is obtained as syrup (274 mg).

Workup

  1. stirringThe reaction mixture is stirred for 20 hours at room temperature
  2. extractionthe resulting mixture is extracted with ethyl acetate (30 ml)
  3. washThe organic phase is washed twice with water
  4. dry with materialdried over Na2SO4
  5. filtrationAfter filtration and evaporation of volatiles
  6. customthe crude product is purified by two consecutive chromatographies on silicagel (CH2Cl2/MeOH gradient

Sources & evidence

ORD record
ord-a2d49713624d457592f97f590f6d5424
Source dataset
uspto-grants-2012_05
Patent number
US08178533B2

Reaction notes

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