2-Bromothiazole → HCID 19875966, compound

HRID 1886418Notes

Reaction equation

HRID 1886418 reaction equation
Br[C:2]1[S:3][CH:4]=[CH:5][N:6]=1.[NH2:7][CH2:8][CH2:9][N:10]1[CH2:14][CH2:13][CH:12]([NH:15][C:16]2[N:20]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[C:19]3[CH:29]=[CH:30][CH:31]=[CH:32][C:18]=3[N:17]=2)[CH2:11]1>N1C=CC=CC=1>[F:28][C:25]1[CH:26]=[CH:27][C:22]([CH2:21][N:20]2[C:19]3[CH:29]=[CH:30][CH:31]=[CH:32][C:18]=3[N:17]=[C:16]2[NH:15][CH:12]2[CH2:13][CH2:14][N:10]([CH2:9][CH2:8][NH:7][C:2]3[S:3][CH:4]=[CH:5][N:6]=3)[CH2:11]2)=[CH:23][CH:24]=1

Participants

4

Reactant 2

HCID 764302-Bromothiazole2×HCID 15037482HCID 15037482, compound

Product 1

HCID 19875966HCID 19875966, compoundYield 7.3%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A mixture of 12.8 parts of 2-bromothiazole, 22 parts of N-[1-(2-amino ethyl)-3-pyrrolidinyl]-1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-amine and 250 parts of pyridine was stirred and refluxed for 6 hours. After cooling, 12.8 parts of 2-bromothiazole were added and stirring was continued overnight at reflux temperature. The mixture was cooled and evaporated. The residue was taken up three times in methylbenzene and the latter was evaporated each time. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane, hexane, methanol and ammonium hydroxide (45:45:10:1 by volume) as eluent. The pure and the less pure fractions were collected and the eluent was evaporated. The residue was purified by column chromatography (HPLC) over silica gel using a mixture of trichloromethane, methanol and methanol, saturated with ammonia, (96:3:1 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from a mixture of 2,2'-oxybispropane and 2-propanone. The product was filtered off and dried, yielding 2.0 parts (7.3%) of 1-[(4-fluorophenyl)methyl]-N-[1-[2-(2-thiazolylamino)ethyl]-3-pyrrolidinyl]-1H-benzimidazol-2-amine; mp. 127.1° C. (compound 168).

Workup

  1. temperaturerefluxed for 6 hours
  2. temperatureAfter cooling
  3. stirringstirring
  4. temperatureat reflux temperature
  5. temperatureThe mixture was cooled
  6. customevaporated
  7. customthe latter was evaporated each time
  8. customThe residue was purified by column chromatography over silica gel using
  9. additiona mixture of trichloromethane, hexane, methanol and ammonium hydroxide (45:45:10:1 by volume) as eluent
  10. customThe pure and the less pure fractions were collected
  11. customthe eluent was evaporated
  12. customThe residue was purified by column chromatography (HPLC) over silica gel using
  13. additiona mixture of trichloromethane, methanol and methanol
  14. customThe pure fractions were collected
  15. customthe eluent was evaporated
  16. customThe residue was crystallized from a mixture of 2,2'-oxybispropane and 2-propanone
  17. filtrationThe product was filtered off
  18. customdried

Sources & evidence

ORD record
ord-58a168bafb724f31a5e5e69341df274b
Source dataset
uspto-grants-1992_09
Patent number
US05151424

Reaction notes

Loading…