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

HRID 1067280Notes

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.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

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-oxopentancate (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

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

Sources & evidence

ORD record: ord-a097c6beafe647a6a5d4cc840ee2de63
Source dataset: uspto-grants-2001_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06248747B1

Reaction notes

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