Dimethylformamide → HCID 131731381, compound

HRID 1021288Notes

Reaction equation

HRID 1021288 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][CH:7]([C:10](O)=O)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].C(Cl)(=O)[C:14](Cl)=[O:15].[NH2:19][C:20]1[N:25]=[CH:24][C:23]([C:26]2[C:27]([F:34])=[C:28]([CH:31]=[CH:32][CH:33]=2)[CH:29]=[O:30])=[CH:22][N:21]=1.CN(C=O)C>ClCCl.CN(C=O)C.O.C(Cl)(Cl)Cl>[C:1]([N:4]1[CH2:5][CH2:6][CH:7]([CH2:10][C:14]([NH:19][C:20]2[N:25]=[CH:24][C:23]([C:26]3[CH:33]=[CH:32][CH:31]=[C:28]([CH:29]=[O:30])[C:27]=3[F:34])=[CH:22][N:21]=2)=[O:15])[CH2:8][CH2:9]1)(=[O:3])[CH3:2]

Participants

9

Reactant 4

HCID 6228Dimethylformamide4×HCID 65578Oxalyl chloride5×HCID 1172551-Acetylpiperidine-4-carboxylic acid5×HCID 88930866HCID 88930866, compound

Product 1

HCID 131731381HCID 131731381, compoundYield 120.7%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent5×

Procedure

1-Acetylpiperidine-4-carboxylic acid (161 mg) was mixed with dichloromethane (5 ml), and oxalyl chloride (124 mg) and DMF (3 mg) were added thereto, followed by stirring at room temperature for 1 hour. TEA and 3-(2-aminopyrimidin-5-yl)-2-fluorobenzaldehyde (170 mg) were added thereto at 0° C., followed by stirring at room temperature overnight. A mixture of 1-acetylpiperidine-4-carboxylic acid (161 mg), oxalyl chloride (0.084 ml), and DMF in dichloromethane (3 ml), which is mixed in advance and was stirred for 1 hour, was added thereto at 0° C., followed by stirring at room temperature for 3 hours. Furthermore, a mixture of 1-acetylpiperidine-4-carboxylic acid (161 mg), oxalyl chloride (0.084 ml), and DMF in dichloromethane (3 ml), after mixing with the reaction mixture in advance, and then stirring for 1 hour, was added thereto at 0° C., followed by stirring at room temperature overnight. Furthermore, a mixture of 1-acetylpiperidine-4-carboxylic acid (322 mg), oxalyl chloride (0.168 ml), and DMF in dichloromethane (6 ml) which is mixed in advance and was stirred for 1 hour, was added thereto at 0° C., followed by stirring at room temperature for 3 hours. Furthermore, a mixture of 1-acetylpiperidine-4-carboxylic acid (322 mg), oxalyl chloride (0.168 ml), and DMF in dichloromethane (6 ml) which is mixed in advance and was stirred for 1 hour, was added thereto at 0° C., followed by stirring at room temperature overnight. CHCl3 and water were added to the reaction mixture, and the insoluble matter was removed by filtration. The organic layer was washed with water and saturated brine, dried over Na2SO4, and then concentrated under reduced pressure. The obtained residue was mixed with MeOH, and NaHCO3 was added thereto, followed by stirring at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (MeOH/CHCl3) to obtain 1-acetyl-N-[5-(2-fluoro-3-formylphenyl)pyrimidin-2-yl]piperidine-4-carboxyamide (363 mg).

Workup

  1. additionwere added
  2. customat 0° C.
  3. stirringby stirring at room temperature overnight
  4. additionis mixed in advance
  5. stirringwas stirred for 1 hour
  6. additionwas added
  7. customat 0° C.
  8. stirringby stirring at room temperature for 3 hours
  9. additionafter mixing with the reaction mixture in advance
  10. stirringstirring for 1 hour
  11. additionwas added
  12. customat 0° C.
  13. stirringby stirring at room temperature overnight
  14. additionis mixed in advance
  15. stirringwas stirred for 1 hour
  16. additionwas added
  17. customat 0° C.
  18. stirringby stirring at room temperature for 3 hours
  19. additionis mixed in advance
  20. stirringwas stirred for 1 hour
  21. additionwas added
  22. customat 0° C.
  23. stirringby stirring at room temperature overnight
  24. customthe insoluble matter was removed by filtration
  25. washThe organic layer was washed with water and saturated brine
  26. dry with materialdried over Na2SO4
  27. concentrationconcentrated under reduced pressure
  28. additionThe obtained residue was mixed with MeOH, and NaHCO3
  29. additionwas added
  30. stirringby stirring at room temperature overnight
  31. concentrationThe reaction mixture was concentrated under reduced pressure
  32. customthe residue was purified by silica gel column chromatography (MeOH/CHCl3)

Sources & evidence

ORD record
ord-10241f701fa6423c80e5bbabc60c900b
Source dataset
uspto-grants-2014_05
Patent number
US08716470B2

Reaction notes

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