Sodium hydride → HCID 14855049, compound

HRID 1165057Notes

Reaction equation

HRID 1165057 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([OH:7])=[CH:3][CH:2]=1.[H-].[Na+].F[B-](F)(F)F.[NH2:15][C:16]1[C:58]([Cl:59])=[CH:57][C:19]([C:20]([NH:22][C@H:23]2[CH2:28][CH2:27][N:26]([CH2:29][CH2:30][N+]3C(C4C=CC=CC=4)=CC(C4C=CC=CC=4)=CC=3C3C=CC=CC=3)[CH2:25][C@H:24]2[O:55][CH3:56])=[O:21])=[C:18]([O:60][CH3:61])[CH:17]=1>CC1C=CC=CC=1>[NH2:15][C:16]1[C:58]([Cl:59])=[CH:57][C:19]([C:20]([NH:22][C@H:23]2[CH2:28][CH2:27][N:26]([CH2:29][CH2:30][O:7][C:4]3[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=3)[CH2:25][C@H:24]2[O:55][CH3:56])=[O:21])=[C:18]([O:60][CH3:61])[CH:17]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 86743794HCID 86743794, compoundHCID 178418642HCID 178418642, compound

Product 1

HCID 14855049HCID 14855049, compoundYield 28.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

A mixture of 2.36 parts of 4-pyridinol, 1.2 parts of a sodium hydride dispersion 50% and 18 parts of methylbenzene was stirred for 2 hours at room temperature. A solution of 7.1 parts of cis-1-[2-[4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-3-methoxy-1-piperidinyl]ethyl]-2,4,6-triphenylpyridinium tetrafluoroborate in 9 parts of methylbenzene was added and stirring was continued first for 4 hours at reflux temperature and then overnight at room temperature. The whole was extracted five times with 100 parts of a hydrochloric acid solution 1N. The combined acid aqueous phases were treated with potassium hydroxide and extracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was purified twice by column chromatography over silica gel using first a mixture of trichloromethane and methanol, saturated with ammonia, (90:10 by volume) and then 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 1.23 parts (28.3%) of cis-4-amino-5-chloro-2-methoxy-N-[3methoxy-1-[2-(4-pyridinyloxy)ethyl]-4piperidinyl]benzamide; mp. 212.2° C. (compound 60).

Workup

  1. stirringstirring
  2. waitwas continued first for 4 hours
  3. temperatureat reflux temperature
  4. customovernight
  5. customat room temperature
  6. extractionThe whole was extracted five times with 100 parts of a hydrochloric acid solution 1N
  7. additionThe combined acid aqueous phases were treated with potassium hydroxide
  8. extractionextracted with dichloromethane
  9. customThe extract was dried
  10. filtrationfiltered
  11. customevaporated
  12. customThe residue was purified twice by column chromatography over silica gel using first
  13. additiona mixture of trichloromethane and methanol
  14. additionsaturated with ammonia, (90:10 by volume) and then a mixture of trichloromethane and methanol
  15. customThe pure fractions were collected
  16. customthe eluent was evaporated
  17. customThe residue was crystallized from acetonitrile
  18. filtrationThe product was filtered off
  19. customdried

Sources & evidence

ORD record
ord-03bca7e1cd5e40ae83739049828290e2
Source dataset
uspto-grants-1990_03
Patent number
US04906643

Reaction notes

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