Methyl Isobutyl Ketone → HCID 131716770, compound

HRID 1460532Notes

Reaction equation

HRID 1460532 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[CH2:23][CH2:22][NH:21][CH2:20]2)=[CH:4][CH:3]=1.[C:24](=[O:27])([O-:26])[O-].[Na+].[Na+].CC(C)C[C:33](=[O:35])C.Cl[CH2:38][CH2:39][N:40]1[C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=2[NH:42][C:41]1=[O:49]>O>[C:33]([OH:35])(=[O:49])[C:24]([OH:26])=[O:27].[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[CH2:23][CH2:22][N:21]([CH2:38][CH2:39][N:40]3[C:44]4[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=4[NH:42][C:41]3=[O:49])[CH2:20]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 7909Methyl Isobutyl KetoneHCID 10340Sodium CarbonateHCID 36534711-(2-Chloroethyl)-1,3-dihydro-2H-benzimidazol-2-oneHCID 15037382HCID 15037382, compound

Product 1

HCID 131716770HCID 131716770, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A mixture of 6.2 parts of 1-[(4-fluorophenyl)methyl]-N-(3-pyrrolidinyl)-1H-benzimidazol-2-amine, 4.3 parts of sodium carbonate and 120 parts of 4-methyl-2-pentanone was stirred and refluxed for 30 minutes using a water separator. 4.9 Parts of 1-(2-chloroethyl)-1,3-dihydro-2H-benzimidazol-2-one were added at reflux temperature and stirring was continued for 20 hours at reflux temperature using a water separator. After cooling, the salts were filtered off and the filtrate was washed with water, dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane, methanol and ammonium hydroxide (90:9:1 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was converted into the ethanedioate salt in 2-propanone. The salt was filtered off and dried in a dry pistol with methylbenzene, yielding 6.30 parts (45%) of 1-[2-[3-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-pyrrolidinyl]ethyl]-1,3-dihydro-2H-benzimidazol-2-one ethanedioate(2:5); mp. 190.6° C. (compound 125).

Workup

  1. temperaturerefluxed for 30 minutes
  2. temperatureat reflux temperature
  3. stirringstirring
  4. temperatureat reflux temperature
  5. temperatureAfter cooling
  6. filtrationthe salts were filtered off
  7. washthe filtrate was washed with water
  8. customdried
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified by column chromatography over silica gel using
  12. additiona mixture of trichloromethane, methanol and ammonium hydroxide (90:9:1 by volume) as eluent
  13. customThe pure fractions were collected
  14. customthe eluent was evaporated
  15. filtrationThe salt was filtered off
  16. dry with materialdried in a dry pistol with methylbenzene

Sources & evidence

ORD record
ord-695ef45710bc4b95b57602ca2d14e185
Source dataset
uspto-grants-1991_12
Patent number
US05071846

Reaction notes

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