Diisopropylethylamine → 2-(2-bromo-acetylamino)-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-benzamide

HRID 1865634Notes

Reaction equation

HRID 1865634 reaction equation
[NH2:1][C:2]1[CH:12]=[CH:11][C:10]([C:13]2[CH:14]=[C:15]3[C:21]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[O:28][CH3:29])=[N:20][N:19]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:16]3=[N:17][CH:18]=2)=[CH:9][C:3]=1[C:4]([N:6]([CH3:8])[CH3:7])=[O:5].C(N(C(C)C)CC)(C)C.[Br:47][CH2:48][C:49](Cl)=[O:50]>ClCCl>[Br:47][CH2:48][C:49]([NH:1][C:2]1[CH:12]=[CH:11][C:10]([C:13]2[CH:14]=[C:15]3[C:21]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[O:28][CH3:29])=[N:20][N:19]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:16]3=[N:17][CH:18]=2)=[CH:9][C:3]=1[C:4]([N:6]([CH3:8])[CH3:7])=[O:5])=[O:50]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 89602Bromoacetyl chlorideHCID 579757432-amino-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanylethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-benzamide

Product 1

HCID 579758972-(2-bromo-acetylamino)-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-benzamideYield 87.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

285 mg (0.55 mmol) of 2-amino-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-benzamide was dissolved in 25 mL of dichloromethane. 175 μL (132 mg, 1.02 mmol) of di-iso-propylethylamine was added and the solution cooled to 0° C. 110 μL (208 mg, 1.32 mmol) of bromoacetyl chloride was added in two portions within 2 h while stirring at 0° C. Upon complete addition the mixture was stirred for 19 h, allowing to warm to ambient temperature. The resulting solution was evaporated and the residue directly purified by flash chromatography on silica gel using a gradient of ethyl acetate containing 15% of methanol in hexanes to afford 306 mg (0.48 mmol, 87%) of 2-(2-bromo-acetylamino)-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-benzamide as a tan solid. MS: m/z 637.9+640.0 (M+H+).

Workup

  1. additionUpon complete addition the mixture
  2. stirringwas stirred for 19 h
  3. temperatureto warm to ambient temperature
  4. customThe resulting solution was evaporated
  5. customthe residue directly purified by flash chromatography on silica gel using a gradient of ethyl acetate containing 15% of methanol in hexanes

Sources & evidence

ORD record
ord-88653c5015254efebd53327f6dc2b587
Source dataset
uspto-grants-2009_12
Patent number
US07626021B2

Reaction notes

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