Dimethylformamide → ethyl 4-[[3-(2-ethoxyethyl)-3H-imidazo[4,5-b] pyridin-2-yl](phenylmethyl)amino]-1-piperidinecarboxylate

HRID 2166148Notes

Reaction equation

HRID 2166148 reaction equation
[H-].[Na+].CN(C)C=O.[CH2:8]([O:10][CH2:11][CH2:12][N:13]1[C:17]2=[N:18][CH:19]=[CH:20][CH:21]=[C:16]2[N:15]=[C:14]1[NH:22][CH:23]1[CH2:28][CH2:27][N:26]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:25][CH2:24]1)[CH3:9].Br[CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>O>[CH2:8]([O:10][CH2:11][CH2:12][N:13]1[C:17]2=[N:18][CH:19]=[CH:20][CH:21]=[C:16]2[N:15]=[C:14]1[N:22]([CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[CH:23]1[CH2:28][CH2:27][N:26]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:25][CH2:24]1)[CH3:9]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 15718792ethyl 4-[[3-(2-ethoxyethyl)-3H-imidazo[4,5-b]pyridin-2-yl]amino]-1-piperidinecarboxylate

Product 1

HCID 15718984ethyl 4-[[3-(2-ethoxyethyl)-3H-imidazo[4,5-b] pyridin-2-yl](phenylmethyl)amino]-1-piperidinecarboxylateYield 13.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 2.7 parts of a sodium hydride dispersion 50% and 282 parts of N,N-dimethylformamide was stirred at room temperature under nitrogen atmosphere. 18.8 Parts of ethyl 4-[[3-(2-ethoxyethyl)-3H-imidazo[4,5-b]pyridin-2-yl]amino]-1-piperidinecarboxylate were added portionwise to the previous mixture. Upon complete addition, stirring for continued for 1 hour at room temperature. 10 Parts of (bromomethyl)benzene were added dropwise and upon completion, stirring was continued for 1 hour. The reaction mixture was decomposed with water and the product was extracted with 4-methyl-2-pentanone. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and ethanol (98:2 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from 2,2'-oxybispropane. The product was filtered off and dried, yielding 3.2 parts (13.6%) of ethyl 4-[[3-(2-ethoxyethyl)-3H-imidazo[4,5-b] pyridin-2-yl](phenylmethyl)amino]-1-piperidinecarboxylate; mp. 115.0° C. (compound 177).

Workup

  1. additionUpon complete addition
  2. stirringstirring
  3. stirringstirring
  4. waitwas continued for 1 hour
  5. extractionthe product was extracted with 4-methyl-2-pentanone
  6. customThe extract was dried
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by column chromatography over silica gel using
  10. additiona mixture of trichloromethane and ethanol (98:2 by volume) as eluent
  11. customThe pure fractions were collected
  12. customthe eluent was evaporated
  13. customThe residue was crystallized from 2,2'-oxybispropane
  14. filtrationThe product was filtered off
  15. customdried

Sources & evidence

ORD record
ord-98932a38568141b491c5591bd88bd2c5
Source dataset
uspto-grants-1990_07
Patent number
US04943580

Reaction notes

Loading…