Sodium hydride → tert-butyl N-{2-(tert-butyldimethylsilyloxy)ethyl}-N-{[1-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazol-4-yl]carbonyl}glycinate

HRID 1928662Notes

Reaction equation

HRID 1928662 reaction equation
[Si:1]([O:8][CH2:9][CH2:10][NH:11][C:12]([C:14]1[CH:15]=[N:16][N:17]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:33][CH2:32][CH2:31][C@H:30]3[CH3:34])=[CH:21][CH:20]=2)[CH:18]=1)=[O:13])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:38][C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40]>CN(C)C=O.O>[Si:1]([O:8][CH2:9][CH2:10][N:11]([C:12]([C:14]1[CH:15]=[N:16][N:17]([C:19]2[CH:20]=[CH:21][C:22]([O:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:33][CH2:32][CH2:31][C@H:30]3[CH3:34])=[CH:23][CH:24]=2)[CH:18]=1)=[O:13])[CH2:38][C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 59541712N-{2-(tert-butyldimethylsilyloxy)ethyl}-1-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazole-4-carboxamide

Product 1

HCID 59541725tert-butyl N-{2-(tert-butyldimethylsilyloxy)ethyl}-N-{[1-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazol-4-yl]carbonyl}glycinateYield 25.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of N-{2-(tert-butyldimethylsilyloxy)ethyl}-1-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazole-4-carboxamide prepared in Example 67-(1) (0.700 g) in N,N-dimethylformamide (5.0 mL), sodium hydride (55% in mineral oil, 0.058 g) was added and stirred at room temperature for 20 minutes. To the reaction mixture, tert-butyl 2-bromoacetate (0.281 g) was added and stirred for 30 minutes. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluting solvent: n-hexane:ethyl acetate=1:1) to give the titled compound (0.220 g) as a colorless oil.

Workup

  1. stirringstirred for 30 minutes
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by silica gel column chromatography (eluting solvent: n-hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-1f6f4e50b5f94fe798b5cb2a0a62c8b1
Source dataset
uspto-grants-2012_05
Patent number
US08183387B2

Reaction notes

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