o-Xylyl bromide → 2-[5-[1-(2-Methyl-benzyl)-1H-pyrazol-4-ylcarbamoyl]-2-oxo-1-(2-trimethylsilanyl-ethoxymethyl)-1,2-dihydro-pyridin-3-yl]-indole-1-carboxylic acid tert-butyl ester

HRID 1406396Notes

Reaction equation

HRID 1406396 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:17]1[C:18](=[O:39])[N:19]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[CH:20]=[C:21]([C:23](=[O:30])[NH:24][C:25]2[CH:26]=[N:27][NH:28][CH:29]=2)[CH:22]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].[CH3:46][C:47]1[CH:54]=[CH:53][CH:52]=[CH:51][C:48]=1[CH2:49]Br>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:17]1[C:18](=[O:39])[N:19]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:36])([CH3:37])[CH3:38])[CH:20]=[C:21]([C:23](=[O:30])[NH:24][C:25]2[CH:29]=[N:28][N:27]([CH2:46][C:47]3[CH:54]=[CH:53][CH:52]=[CH:51][C:48]=3[CH3:49])[CH:26]=2)[CH:22]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6992o-Xylyl bromideHCID 10796Cesium carbonateHCID 581172532-[2-Oxo-5-(1H-pyrazol-4-ylcarbamoyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1,2-dihydro-pyridin-3-yl]-indole-1-carboxylic acid tert-butyl ester2×

Product 1

HCID 581173472-[5-[1-(2-Methyl-benzyl)-1H-pyrazol-4-ylcarbamoyl]-2-oxo-1-(2-trimethylsilanyl-ethoxymethyl)-1,2-dihydro-pyridin-3-yl]-indole-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Intermediate (2d), 2-[2-oxo-5-(1H-pyrazol-4-ylcarbamoyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1,2-dihydro-pyridin-3-yl]-indole-1-carboxylic acid tert-butyl ester (50 mg, 0.091 mmol), Cs2CO3 (45 mg, 0.136 mmol) and 2-methylbenzyl bromide (21 mg, 15 ul, 0.11 mmol) were stirred in N,N-dimethylformamide (5 mL) at ambient temperature for 48 hours. The inorganics were separated via filtration and the filtrate was concentrated in vacuo. The resultant crude product was purified by flash chromatography on SiO2 eluting with hexane—50% ethyl acetate/hexane (gradient) to afford the desired title compound as a solid, 55 mg, 93%.

Workup

  1. customThe inorganics were separated via filtration
  2. concentrationthe filtrate was concentrated in vacuo
  3. customThe resultant crude product was purified by flash chromatography on SiO2 eluting with hexane—50% ethyl acetate/hexane (gradient)

Sources & evidence

ORD record
ord-529034b53c60411483cdf7ab8c178c40
Source dataset
uspto-grants-2014_12
Patent number
US08916591B2

Reaction notes

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