Hydrochloric Acid → cis-4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-[4-(methylamino)butyl]-4-piperidinyl]benzamide

HRID 1165037Notes

Reaction equation

HRID 1165037 reaction equation
[NH2:1][C:2]1[C:31]([Cl:32])=[CH:30][C:5]([C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][N:19](C)[C:20](=O)OC(C)(C)C)[CH2:11][C@H:10]2[O:28][CH3:29])=[O:7])=[C:4]([O:33][CH3:34])[CH:3]=1.Cl>CC(O)C>[NH2:1][C:2]1[C:31]([Cl:32])=[CH:30][C:5]([C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][NH:19][CH3:20])[CH2:11][C@H:10]2[O:28][CH3:29])=[O:7])=[C:4]([O:33][CH3:34])[CH:3]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 67922785(1,1-Dimethylethyl) cis-[4-[4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-3-methoxy-1-piperidinyl]butyl]methylcarbamate

Product 1

HCID 14854963cis-4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-[4-(methylamino)butyl]-4-piperidinyl]benzamideYield 78.7%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of (1,1-dimethylethyl) cis-[4-[4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-3-methoxy-1-piperidinyl]butyl]methylcarbamate and 250 parts of 2-propanol, saturated with hydrochloric acid was stirred and refluxed for 15 minutes. The reaction mixture was evaporated and the residue was taken up in trichloromethane. The organic layer was washed with water, saturated with ammonium hydroxide, dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol, saturated with ammonia, (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding 33 parts (78.7%) of cis-4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-[4-(methylamino)butyl]-4-piperidinyl]benzamide; mp. 129.3° C. (interm. 9).

Workup

  1. temperaturerefluxed for 15 minutes
  2. customThe reaction mixture was evaporated
  3. washThe organic layer was washed with water, saturated with ammonium hydroxide
  4. customdried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by column chromatography over silica gel using
  8. additiona mixture of trichloromethane and methanol
  9. customThe pure fractions were collected
  10. customthe eluent was evaporated
  11. customThe residue was crystallized from acetonitrile
  12. filtrationThe product was filtered off
  13. customdried

Sources & evidence

ORD record
ord-0c993dd33c904aa2b79ab064e06c236b
Source dataset
uspto-grants-1990_03
Patent number
US04906643

Reaction notes

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