Thioacetamide → HCID 14013059, compound

HRID 2309648Notes

Reaction equation

HRID 2309648 reaction equation
[C:1](=[S:4])([NH2:3])[CH3:2].Br.Br.Br[CH2:8][C:9](=O)[CH2:10][CH2:11][N:12]1[CH2:17][CH2:16][CH:15]([CH2:18][C:19]2[N:23]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[C:22]3[CH:32]=[CH:33][CH:34]=[CH:35][C:21]=3[N:20]=2)[CH2:14][CH2:13]1>CO>[F:31][C:28]1[CH:29]=[CH:30][C:25]([CH2:24][N:23]2[C:22]3[CH:32]=[CH:33][CH:34]=[CH:35][C:21]=3[N:20]=[C:19]2[CH2:18][CH:15]2[CH2:14][CH2:13][N:12]([CH2:11][CH2:10][C:9]3[N:3]=[C:1]([CH3:2])[S:4][CH:8]=3)[CH2:17][CH2:16]2)=[CH:26][CH:27]=1

Participants

4

Reactant 2

HCID 2723949ThioacetamideHCID 20037945HCID 20037945, compound

Product 1

HCID 14013059HCID 14013059, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 0.75 parts of ethanethioamide, 7 parts of 1-bromo-4-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]methyl]-1-piperidinyl]-2-butanone dihydrobromide and 80 parts of methanol was stirred overnight at room temperature. The reaction mixture was evaporated. Water was added. The whole was treated with sodium hydroxide. The product was extracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol, saturated with ammonia, (97:3 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was further purified by column chromatography (HPLC) over silica gel using a mixture of hexane, trichloromethane and methanol (45:45:10 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was converted into the ethanedioate salt in ethanol and 2-propanone. The salt was filtered off and dried, yielding 2 parts (33%) of 1-[(4-fluorophenyl)methyl]-2-[[1-[2-(2-methyl-4-thiazolyl)ethyl]-4-piperidinyl]methyl]-1H-benzimidazole ethanediote(2:5); mp. 124.1° C. (459).

Workup

  1. customThe reaction mixture was evaporated
  2. additionWater was added
  3. additionThe whole was treated with sodium hydroxide
  4. extractionThe product was extracted with dichloromethane
  5. customThe extract was dried
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by column chromatography over silica gel using
  9. additiona mixture of trichloromethane and methanol
  10. customThe pure fractions were collected
  11. customthe eluent was evaporated
  12. customThe residue was further purified by column chromatography (HPLC) over silica gel using
  13. additiona mixture of hexane, trichloromethane and methanol (45:45:10 by volume) as eluent
  14. customThe pure fractions were collected
  15. customthe eluent was evaporated
  16. filtrationThe salt was filtered off
  17. customdried

Sources & evidence

ORD record
ord-c035f14c94b84db5bccd479da418a4ba
Source dataset
uspto-grants-1987_09
Patent number
US04695575

Reaction notes

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