Carbamimidic acid, methyl ester, sulfate (1:1) → HCID 178494183, compound

HRID 2086906Notes

Reaction equation

HRID 2086906 reaction equation
[CH2:1]([O:8][C:9]([C:11]1[CH:16]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[C:19]([F:24])[CH:18]=2)[NH:15][C:14]([O:25][CH3:26])=[N:13][C:12]=1[CH2:27]C)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC1C=C(C=C(C(=O)C)CC(OCC2C=CC=CC=2)=O)C=CC=1F.S(O)(O)(=O)=O.COC(=N)N.C([O-])(O)=O.[Na+]>CN(C=O)C>[CH2:1]([O:8][C:9]([C:11]1[CH:16]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[C:19]([F:24])[CH:18]=2)[NH:15][C:14]([O:25][CH3:26])=[N:13][C:12]=1[CH3:27])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 169039Carbamimidic acid, methyl ester, sulfate (1:1)HCID 516892Sodium BicarbonateHCID 54072301HCID 54072301, compoundHCID 178436962HCID 178436962, compound

Product 1

HCID 178494183HCID 178494183, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

5-(Benzyloxycarbonyl)-1,6-dihydro-2-methoxy-4-ethyl-6-(3,4-difluorophenyl)pyrimidine. A suspension of benzyl 3-[(3,4-difluorophenyl)methylene]-4-oxopentanoate (16.0 g, 48.0 mmol), O-methylisourea hydrogen sulfate (16.65 g, 97.02 mmol), NaHCO3 (16.3 g, 130.2 mmol) in DMF (190 mL) was stirred at 70° C. for 20 h. After cooling to room temperature, the mixture was filtered and the filtrate was diluted with EtOAc (300 mL) and then washed with water (4×100 mL), brine (200 mL) and dried over Na2SO4. After removal of solvent, the residue was purified by column chromatography (SiO2, EtOAc/Hexane, 10%-30%) to get 5-(benzyloxycarbonyl)-1,6-dihydro-2-methoxy-4-methyl-6-(3,4-difluorophenyl)pyrimidine as a colorless oil (10.6 g, 58%). The NMR analysis showed it to be a mixture of amine/imine tautomers and was used as is in the next step.

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationthe mixture was filtered
  3. additionthe filtrate was diluted with EtOAc (300 mL)
  4. washwashed with water (4×100 mL), brine (200 mL)
  5. dry with materialdried over Na2SO4
  6. customAfter removal of solvent
  7. customthe residue was purified by column chromatography (SiO2, EtOAc/Hexane, 10%-30%)

Sources & evidence

ORD record
ord-ce9973e60fd44a00acf4056477c7377c
Source dataset
uspto-grants-2004_04
Patent number
US06727257B1

Reaction notes

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