Sodium hydride → 2-(5-methoxy-3-(1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridin-7-yl)-1H-indol-1-yl)-N,N-dimethylacetamide

HRID 1628074Notes

Reaction equation

HRID 1628074 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[C:12]1[N:24]([S:25]([C:28]2[CH:34]=[CH:33][C:31]([CH3:32])=[CH:30][CH:29]=2)(=[O:27])=[O:26])[C:15]2=[N:16][CH:17]=[C:18]3[CH:22]=[N:21][N:20]([CH3:23])[C:19]3=[C:14]2[CH:13]=1.[H-].[Na+].Cl[CH2:38][C:39]([N:41]([CH3:43])[CH3:42])=[O:40]>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:38][C:39]([N:41]([CH3:43])[CH3:42])=[O:40])[CH:7]=[C:6]2[C:12]1[N:24]([S:25]([C:28]2[CH:34]=[CH:33][C:31]([CH3:32])=[CH:30][CH:29]=2)(=[O:27])=[O:26])[C:15]2=[N:16][CH:17]=[C:18]3[CH:22]=[N:21][N:20]([CH3:23])[C:19]3=[C:14]2[CH:13]=1

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 758862-chloro-N,N-dimethylacetamideHCID 583821087-(5-methoxy-1H-indol-3-yl)-1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine

Product 1

HCID 583821812-(5-methoxy-3-(1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridin-7-yl)-1H-indol-1-yl)-N,N-dimethylacetamideYield 82.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

7-(5-Methoxy-1H-indol-3-yl)-1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine (0.100 g, 0.212 mmol; Preparation #P.1.1) and 60 wt % NaH (0.009 g, 0.212 mmol) were suspended in DMF (3 mL). After about 10 min, 2-chloro-N,N-dimethylacetamide (0.052 g, 0.424 mmol, Pfaltz-Bauer) was added and mixture was stirred at rt. After about 1 h additional 60 wt % NaH (0.005 g, 0.212 mmol) was added and the mixture was heated to about 40° C. for about 16 h. The mixture was concentrated in vacuo and purified on a 4 g silica column eluting with EtOAc to provide 2-(5-methoxy-3-(1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridin-7-yl)-1H-indol-1-yl)-N,N-dimethylacetamide (0.097 g, 82%): LC/MS (Table 2, Method c) Rt=1.46 min; MS m/z 557 (M+H)+.

Workup

  1. temperaturethe mixture was heated to about 40° C. for about 16 h
  2. concentrationThe mixture was concentrated in vacuo
  3. custompurified on a 4 g silica column
  4. washeluting with EtOAc

Sources & evidence

ORD record
ord-d750577d1fa242b687409ff790bf000f
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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