Sulfuric Acid → HCID 86744270, compound

HRID 345603Notes

Reaction equation

HRID 345603 reaction equation
S(=O)(=O)(O)O.[NH2:6][C:7]1[C:31]([C:32]#[N:33])=[CH:30][C:10]([C:11]([NH:13][C@H:14]2[CH2:19][CH2:18][N:17]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)[CH2:16][C@H:15]2[O:28][CH3:29])=[O:12])=[C:9]([O:34][CH3:35])[CH:8]=1.[OH-:36].[NH4+]>>[NH2:6][C:7]1[CH:8]=[C:9]([O:34][CH3:35])[C:10]([C:11]([NH:13][C@H:14]2[CH2:19][CH2:18][N:17]([CH2:20][C:21]3[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=3)[CH2:16][C@H:15]2[O:28][CH3:29])=[O:12])=[CH:30][C:31]=1[C:32]([NH2:33])=[O:36]

Participants

4

Reactant 3

HCID 1118Sulfuric AcidHCID 14923Ammonium HydroxideHCID 15096820HCID 15096820, compound

Product 1

HCID 86744270HCID 86744270, compound

Procedure

To 65 parts of a sulfuric acid solution 96% were added portionwise (slowly) 3.6 parts of cis-4-amino-5-cyano-N-[1-[(4-fluorophenyl)methyl]-3-methoxy-4-piperidinyl]-2-methoxybenzamide while cooling in an ice-bath. The reaction mixture was allowed to reach room temperature and stirring was continued for 7 hours at room temperature. The reaction mixture was poured onto crushed ice and the whole was alkalized with ammonium hydroxide. The product was extracted with trichloromethane. The extract was washed with water, dried, filtered and evaporated. The residue was purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (90:10 by volume) as eluent. The most pure fractions were collected and the eluent was evaporated. The residue was further purified by HPLC using a mixture of methylbenzene and ethanol (90:10 by volume) as eluent. The pure fraction was collected and the eluent was evaporated. The residue was boiled in acetonitrile. The product was filtered off and dried, yielding 2.67 parts of cis-4-amino-N1 -[1-[(4-fluorophenyl)methyl]-3-methoxy-4-piperidinyl] -6-methoxy-1,3-benzenedicarboxamide; mp. 243.7° C. (compound 234).

Workup

  1. temperaturewhile cooling in an ice-bath
  2. customto reach room temperature
  3. additionThe reaction mixture was poured
  4. customonto crushed ice
  5. extractionThe product was extracted with trichloromethane
  6. washThe extract was washed with water
  7. customdried
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by column-chromatography over silica gel using
  11. additiona mixture of trichloromethane and methanol (90:10 by volume) as eluent
  12. customThe most pure fractions were collected
  13. customthe eluent was evaporated
  14. customThe residue was further purified by HPLC
  15. additiona mixture of methylbenzene and ethanol (90:10 by volume) as eluent
  16. customThe pure fraction was collected
  17. customthe eluent was evaporated
  18. filtrationThe product was filtered off
  19. customdried

Sources & evidence

ORD record
ord-6bc0a17a766e4954a6437f60194062f2
Source dataset
uspto-grants-1991_10
Patent number
US05057525

Reaction notes

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