HCID 14854959, compound → HCID 178493191, compound

HRID 654182Notes

Reaction equation

HRID 654182 reaction equation
CS[C:3]1[N:8]=[C:7]([OH:9])[CH:6]=[CH:5][N:4]=1.[NH2:10][C:11]1[C:31]([Cl:32])=[CH:30][C:14]([C:15]([NH:17][C@H:18]2[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][CH2:26][NH2:27])[CH2:20][C@H:19]2[O:28][CH3:29])=[O:16])=[C:13]([O:33][CH3:34])[CH:12]=1>C(#N)C>[OH2:9].[NH2:10][C:11]1[C:31]([Cl:32])=[CH:30][C:14]([C:15]([NH:17][C@H:18]2[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][CH2:26][NH:27][C:3]3[N:8]=[C:7]([OH:9])[CH:6]=[CH:5][N:4]=3)[CH2:20][C@H:19]2[O:28][CH3:29])=[O:16])=[C:13]([O:33][CH3:34])[CH:12]=1

Participants

4

Reactant 2

HCID 14854959HCID 14854959, compoundHCID 178503462HCID 178503462, compound2×

Product 1

HCID 178493191HCID 178493191, compoundYield 39.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 1.56 parts of 2-(methylthio)-4-pyrimidinol, 3.7 parts of cis-4-amino-N-[1-(3-aminopropyl)-3-methoxy-4-piperidinyl]-5-chloro-2-methoxybenzamide and 64 parts of acetonitrile was stirred for 40 hours at reflux temperature. Another portion of 0.7 parts of 2-(methylthio)-4-pyrimidinol was added and stirring was continued over weekend at reflux temperature. The reaction mixture was evaporated. The residue was taken up in trichloromethane. The whole 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 1.82 parts (39.5%) of cis-4-amino-5-chloro-N-[1-[3-[(4-hydroxy-2-pyrimidinyl)amino]propyl]-3-methoxy-4-piperidinyl]-2-methoxybenzamide monohydrate; mp. 134.2° C. (compound 42).

Workup

  1. temperatureat reflux temperature
  2. stirringstirring
  3. waitwas continued over weekend
  4. temperatureat reflux temperature
  5. customThe reaction mixture was evaporated
  6. washThe whole was washed with water, saturated with ammonium hydroxide
  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
  12. customThe pure fractions were collected
  13. customthe eluent was evaporated
  14. customThe residue was crystallized from acetonitrile
  15. filtrationThe product was filtered off
  16. customdried

Sources & evidence

ORD record
ord-ccf2fcbb1e5849b2b8702b609381d974
Source dataset
uspto-grants-1992_07
Patent number
US05130312

Reaction notes

Loading…