Imidazole → N-{2-(tert-butyldimethylsilyloxy)ethyl}-1-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazole-4-carboxamide

HRID 1364233Notes

Reaction equation

HRID 1364233 reaction equation
[OH:1][CH2:2][CH2:3][NH:4][C:5]([C:7]1[CH:8]=[N:9][N:10]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][CH2:21][N:22]3[CH2:26][CH2:25][CH2:24][C@H:23]3[CH3:27])=[CH:14][CH:13]=2)[CH:11]=1)=[O:6].[C:28]([Si:32](Cl)([CH3:34])[CH3:33])([CH3:31])([CH3:30])[CH3:29].N1C=CN=C1.CN(C)C=O>[Cl-].[Na+].O>[Si:32]([O:1][CH2:2][CH2:3][NH:4][C:5]([C:7]1[CH:8]=[N:9][N:10]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][CH2:21][N:22]3[CH2:26][CH2:25][CH2:24][C@H:23]3[CH3:27])=[CH:14][CH:13]=2)[CH:11]=1)=[O:6])([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:34])[CH3:33]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 6228DimethylformamideHCID 28928tert-Butyldimethylsilyl chlorideHCID 42610555N-(2-hydroxyethyl)-1-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazole-4-carboxamide

Product 1

HCID 59541712N-{2-(tert-butyldimethylsilyloxy)ethyl}-1-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazole-4-carboxamideYield 84.2%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Procedure

A mixture of N-(2-hydroxyethyl)-1-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazole-4-carboxamide prepared in Example 66 (0.500 g), tert-butylchlorodimethylsilane (0.303 g), imidazole (0.273 g) and N,N-dimethylformamide (5.0 mL) was stirred overnight at room temperature. The reaction mixture was diluted with brine 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 (0.550 g) as a colorless solid.

Workup

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

Sources & evidence

ORD record
ord-834b9e121ca64dd7ae3fe3c24d52b7cb
Source dataset
uspto-grants-2011_02
Patent number
US07888354B2

Reaction notes

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