Dimethylformamide → HCID 178498103, compound

HRID 1021325Notes

Reaction equation

HRID 1021325 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][N:18]([C:21]4[CH:30]=[CH:29][C:24]([C:25]([O:27][CH3:28])=[O:26])=[CH:23][C:22]=4[Cl:31])[CH2:17][CH2:16]3)=[N:13][CH:14]=2)[CH:6]=[CH:7][CH:8]=1.C1N=CN([C:37]([N:39]2[CH:43]=[N:42]C=C2)=[O:38])C=1.C[N:45](C=O)C>>[C:43]([NH:39][C:37]([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][N:18]([C:21]4[CH:30]=[CH:29][C:24]([C:25]([O:27][CH3:28])=[O:26])=[CH:23][C:22]=4[Cl:31])[CH2:19][CH2:20]3)=[N:13][CH:14]=2)[CH:6]=[CH:7][CH:8]=1)=[O:38])(=[NH:42])[NH2:45]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 682631,1'-CarbonyldiimidazoleHCID 86686268HCID 86686268, compound

Product 1

HCID 178498103HCID 178498103, compound

Procedure

Methyl 4-(4-{5-[3-(aminomethyl)phenyl]pyrimidin-2-yl}piperazin-1-yl)-3-chlorobenzoate (207 mg) was mixed with DMF (5 ml), and CDI (154 mg) was added thereto at 0° C., followed by stirring at room temperature for 2 hours. 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. The obtained residue was mixed with DMF (5 ml), and guanidine hydrochloride (50 mg) and DBU (204 mg) were added thereto, followed by stirring at 70° C. for 5 hours. 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 basic silica gel column chromatography (CHCl3/MeOH) to obtain methyl 4-{4-[5-(3-{[(carbamimidoylcarbamoyl)amino]methyl}phenyl)pyrimidin-2-yl]piperazin-1-yl}-3-chlorobenzoate (208 mg).

Workup

  1. additionwas added
  2. customat 0° C.
  3. concentrationThe reaction mixture was concentrated under reduced pressure, and EtOAc
  4. additiona saturated aqueous sodium hydrogen carbonate solution were then added
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. additionThe obtained residue was mixed with DMF (5 ml), and guanidine hydrochloride (50 mg) and DBU (204 mg)
  8. additionwere added
  9. stirringby stirring at 70° C. for 5 hours
  10. concentrationThe reaction mixture was concentrated under reduced pressure, water
  11. additionwas then added
  12. filtrationthe insoluble matter was collected by filtration
  13. customThe obtained solid was purified by basic silica gel column chromatography (CHCl3/MeOH)

Sources & evidence

ORD record
ord-64f4260e624e4e8ca75bb43f7fc82c50
Source dataset
uspto-grants-2014_05
Patent number
US08716470B2

Reaction notes

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