Water → N-(1-cyclopentyl-4-piperidinyl)-3-methyl-N-(2-pyrimidinyl)benzeneacetamide ethanedioate

HRID 28152Notes

Reaction equation

HRID 28152 reaction equation
[CH:1]1([N:6]2[CH2:11][CH2:10][CH:9]([NH:12][C:13]3[N:18]=[CH:17][CH:16]=[CH:15][N:14]=3)[CH2:8][CH2:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:19][C:20]1[CH:21]=[C:22]([CH2:26][C:27](Cl)=[O:28])[CH:23]=[CH:24][CH:25]=1.[C:30](=[O:33])([O-:32])[O-].[Na+].[Na+].CC1C=CC=CC=1C.[OH2:44]>>[C:27]([OH:28])(=[O:44])[C:30]([OH:32])=[O:33].[CH:1]1([N:6]2[CH2:11][CH2:10][CH:9]([N:12]([C:13]3[N:14]=[CH:15][CH:16]=[CH:17][N:18]=3)[C:27](=[O:28])[CH2:26][C:22]3[CH:23]=[CH:24][CH:25]=[C:20]([CH3:19])[CH:21]=3)[CH2:8][CH2:7]2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 5

HCID 962WaterHCID 7237O-XyleneHCID 10340Sodium CarbonateHCID 2760633m-Tolylacetyl chloride2×HCID 23339052HCID 23339052, compound

Product 1

HCID 86736170N-(1-cyclopentyl-4-piperidinyl)-3-methyl-N-(2-pyrimidinyl)benzeneacetamide ethanedioate

Procedure

A mixture of 4.5 parts of N-(1-cyclopentyl-4-piperidinyl)-2-pyrimidinamine, 3.4 parts of 3-methylbenzeneacetyl chloride, 2 parts of sodium carbonate and 180 parts of dimethylbenzene is stirred and refluxed for 17 hours. Another 9 parts of 3-methylbenzeneacetyl chloride is added dropwise. Upon completion, stirring is continued for 67 hours at reflux temperature. The reaction mixture is cooled, water is added and the layers are separated. The organic phase is extracted with a diluted hydrochloric acid solution. The combined aqueous phases are washed with benzene and alkalized with a diluted sodium hydroxide solution while cooling in an ice-bath. The product is extracted twice with trichloromethane. The combined extracts are dried, filtered and evaporated. The residue is converted into the ethanedioate salt in 2-propanol. The salt is filtered off and crystallized twice: first from ethanol and then from methanol, yielding 1 part of N-(1-cyclopentyl-4-piperidinyl)-3-methyl-N-(2-pyrimidinyl)benzeneacetamide ethanedioate; mp. 204.1° C.

Workup

  1. temperaturerefluxed for 17 hours
  2. stirringUpon completion, stirring
  3. temperatureat reflux temperature
  4. temperatureThe reaction mixture is cooled
  5. customthe layers are separated
  6. extractionThe organic phase is extracted with a diluted hydrochloric acid solution
  7. washThe combined aqueous phases are washed with benzene
  8. temperaturewhile cooling in an ice-bath
  9. extractionThe product is extracted twice with trichloromethane
  10. customThe combined extracts are dried
  11. filtrationfiltered
  12. customevaporated
  13. filtrationThe salt is filtered off
  14. customcrystallized twice

Sources & evidence

ORD record
ord-f74014f9cb704763a7c550629fcf26f7
Source dataset
uspto-grants-1980_09
Patent number
US04225606

Reaction notes

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