Dimethyl Sulfoxide → HCID 13769699, compound

HRID 979936Notes

Reaction equation

HRID 979936 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]=[C:10]2[NH:18][CH:19]2[CH2:24][CH2:23][N:22]([CH2:25][CH2:26][OH:27])[CH2:21][CH2:20]2)=[CH:4][CH:3]=1.CS(C)=O.[H-].[Na+].Br[C:35]1[S:36][CH:37]=[CH:38][N:39]=1>CC1C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]=[C:10]2[NH:18][CH:19]2[CH2:24][CH2:23][N:22]([CH2:25][CH2:26][O:27][C:35]3[S:36][CH:37]=[CH:38][N:39]=3)[CH2:21][CH2:20]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 24758Sodium hydrideHCID 764302-BromothiazoleHCID 128916994-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-ylamino]-1-piperidineethanol

Product 1

HCID 13769699HCID 13769699, compoundYield 14.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred and cooled (below 10° C.) mixture of 5.52 parts of 4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidine ethanol, 100 parts of dimethyl sulfoxide and 90 parts of methylbenzene were added 0.75 parts of a sodium hydride dispersion 50%. After stirring for 30 minutes at a temperature below 10° C., 2.5 parts of 2-bromothiazole were added and stirring was continued overnight while the mixture was allowed to reach room temperature. The reaction mixture was poured onto 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 methanol (96:4 by volume) saturated with ammonia, as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile, yielding 1 part (14.5%) of 1-[(4-fluorophenyl)methyl]-N-[1-[2-(2-thiazolyloxy)ethyl]- 4-piperidinyl]-1H-benzimidazol-2-amine; mp. 156.5° C. (compound 72).

Workup

  1. temperaturecooled
  2. additionwere added
  3. stirringstirring
  4. customto reach room temperature
  5. additionThe reaction mixture was poured onto water
  6. extractionthe product was extracted with 4-methyl-2-pentanone
  7. customThe extract was dried
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by column chromatography over silica gel using
  11. additiona mixture of trichloromethane and methanol (96:4 by volume) saturated with ammonia
  12. customThe pure fractions were collected
  13. customthe eluent was evaporated
  14. customThe residue was crystallized from acetonitrile

Sources & evidence

ORD record
ord-69869c493f794a50a4d6ee1c2be79114
Source dataset
uspto-grants-1987_01
Patent number
US04634704

Reaction notes

Loading…