Water → HCID 131727076, compound

HRID 33279Notes

Reaction equation

HRID 33279 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][N:8]=[C:9]([C:11]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[O:12][SiH2:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH:10]=1)=[O:5])[CH3:2].Br[CH2:31][C:32]([NH:34][C:35]1[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][N:36]=1)=[O:33].O>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([C:11]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[O:12][SiH2:13][C:14]([CH3:17])([CH3:15])[CH3:16])[N:8]([CH2:31][C:32](=[O:33])[NH:34][C:35]2[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][N:36]=2)[N:7]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 962WaterHCID 34211102-Bromo-N-(5-chloro-2-pyridinyl)acetamideHCID 178469102HCID 178469102, compound

Product 1

HCID 131727076HCID 131727076, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5 g 5-(tert-Butyl-diphenyl-silanyloxymethyl)-2H-pyrazole-3-carboxylic acid ethyl ester in 10 ml DMF 4 g Cs2CO3 and 3 g 2-Bromo-N-(5-chloro-pyridin-2-yl)-acetamide were added and the mixture was stirred for 3 h. Then 10 ml of water were added and the mixture was extracted with ethyl acetate (2×50 ml). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. Inspection of the TLC and HPLC/MS indicated that a 1:1 mixture of the desired product together with the regioisomeric 5-(tert-Butyl-diphenyl-silanyloxymethyl)-2-[(5-chloro-pyridin-2-ylcarbamoyl)-methyl]-2H-pyrazole-3-carboxylic acid ethyl ester was present. Purification of this mixture on silica gel eluting with a gradient on n-heptane/ethylacetate yielded the desired product as the faster eluting less polar isomer.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (2×50 ml)
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. additionInspection of the TLC and HPLC/MS indicated that a 1:1 mixture of the desired product together with the regioisomeric 5-(tert-Butyl-diphenyl-silanyloxymethyl)-2-[(5-chloro-pyridin-2-ylcarbamoyl)-methyl]-2H-pyrazole-3-carboxylic acid ethyl ester
  6. customPurification of this mixture on silica gel eluting with a gradient on n-heptane/ethylacetate

Sources & evidence

ORD record
ord-f7989bcaa46749c4ac7cc92dc3b6735b
Source dataset
uspto-grants-2008_09
Patent number
US07429581B2

Reaction notes

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