Picolyl chloride hydrochloride → HCID 19875959, compound

HRID 1886403Notes

Reaction equation

HRID 1886403 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][CH:11]1[CH2:15][CH2:14][N:13]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:12]1.CN(C)C(=O)C.[H-].[Na+].[ClH:29].[Cl:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=1>O>[ClH:30].[ClH:29].[N:33]1[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=1[CH2:31][N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][CH:11]1[CH2:15][CH2:14][N:13]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:12]1

Participants

6

Reactant 4

HCID 23392Picolyl chloride hydrochlorideHCID 24758Sodium hydrideHCID 31374DimethylacetamideHCID 15037349HCID 15037349, compound

Product 1

HCID 19875959HCID 19875959, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred mixture of 167 parts of ethyl 3-(1H-benzimidazol-2-yl-amino)-1-pyrrolidinecarboxylate and 2790 parts of N,N-dimethylacetamide were added portionwise 61.0 parts of a sodium hydride dispersion 50% Upon completion, stirring was continued for 1 hour at 50° C. 127.2 Parts of 2-(chloromethyl)pyridine hydrochloride were added portionwise at 80° C. After complete addition, the whole was stirred for 2 hours at 80° C. After cooling, the reaction mixture was poured into 1000 parts of water. The product was extracted twice with methylbenzene. The combined extracts were washed with water, dried, filtered and evaporated. The residue was purified twice by column chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 and 99:1 by volume) as eluents. The first and second fractions were collected and the eluent was evaporated. The residue was converted into the hydrochloride salt in 2-propanol and 2,2'-oxybispropane. The salt was filtered off and dried, yielding 69.5 (24%) parts of ethyl 3-[[1-(2-pyridinylmethyl)-1H-benzimidazol-2-yl]amino]-1-pyrrolidinecarboxylate dihydrochloride; mp. >140° C. (compound 23).

Workup

  1. additionAfter complete addition
  2. stirringthe whole was stirred for 2 hours at 80° C
  3. temperatureAfter cooling
  4. extractionThe product was extracted twice with methylbenzene
  5. washThe combined extracts were washed with water
  6. customdried
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified twice by column chromatography over silica gel using
  10. additiona mixture of trichloromethane and methanol (95:5 and 99:1 by volume) as eluents
  11. customThe first and second fractions were collected
  12. customthe eluent was evaporated
  13. filtrationThe salt was filtered off
  14. customdried

Sources & evidence

ORD record
ord-c84642150ba1461785c80435ac2fdc86
Source dataset
uspto-grants-1992_09
Patent number
US05151424

Reaction notes

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