Dimethylformamide → HCID 178469194, compound

HRID 2171727Notes

Reaction equation

HRID 2171727 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([C:9]2[CH:10]=[N:11][C:12]([N:15]3[CH2:20][CH2:19][CH:18]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:17][CH2:16]3)=[N:13][CH:14]=2)[CH:6]=[CH:7][CH:8]=1.C1N=CN([C:31]([N:33]2[CH:37]=[N:36]C=C2)=[O:32])C=1.C[N:39](C=O)C>>[C:37]([NH:33][C:31]([NH:1][CH2:2][C:3]1[CH:4]=[C:5]([C:9]2[CH:10]=[N:11][C:12]([N:15]3[CH2:16][CH2:17][CH:18]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:19][CH2:20]3)=[N:13][CH:14]=2)[CH:6]=[CH:7][CH:8]=1)=[O:32])(=[NH:36])[NH2:39]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 682631,1'-CarbonyldiimidazoleHCID 86686270HCID 86686270, compound

Product 1

HCID 178469194HCID 178469194, compound

Procedure

Ethyl 1-{5-[3-(aminomethyl)phenyl]pyrimidin-2-yl}piperidine-4-carboxylate (303 mg) was mixed with DMF (5 ml), and CDI (188 mg) was added thereto, followed by stirring at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and EtOAc and a saturated aqueous sodium hydrogen carbonate solution were then added thereto. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. Guanidine hydrochloride (170 mg) and sodium hydride (55% suspended in oil) (77 mg) were suspended in DMF (2 ml), and a solution of the reaction mixture obtained immediately before in DMF (1 ml) was added thereto, followed by stirring at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, water was then added thereto, and the insoluble matter was collected by filtration. The obtained solid was purified by silica gel column chromatography (CHCl3/MeOH) to obtain ethyl 1-[5-(3-{[(carbamimidoylcarbamoyl)amino]methyl}phenyl)pyrimidin-2-yl]piperidine-4-carboxylate (74 mg).

Workup

  1. additionwas added
  2. concentrationThe reaction mixture was concentrated under reduced pressure, and EtOAc
  3. additiona saturated aqueous sodium hydrogen carbonate solution were then added
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customa solution of the reaction mixture obtained immediately before in DMF (1 ml)
  7. additionwas added
  8. stirringby stirring at room temperature for 1 hour
  9. concentrationThe reaction mixture was concentrated under reduced pressure, water
  10. additionwas then added
  11. filtrationthe insoluble matter was collected by filtration
  12. customThe obtained solid was purified by silica gel column chromatography (CHCl3/MeOH)

Sources & evidence

ORD record
ord-358eaa07ee354354a81d71b47fb55b02
Source dataset
uspto-grants-2015_06
Patent number
US09051283B2

Reaction notes

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