Carbamimidic acid, methyl ester, sulfate (1:1) → HCID 178436962, compound

HRID 2085416Notes

Reaction equation

[C:1]([C:5](=[CH:16][C:17]1[CH:22]=[C:21]([F:23])[C:20]([F:24])=[C:19](F)[CH:18]=1)[C:6]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7])(=O)[CH2:2][CH3:3].S(O)(O)(=O)=O.[CH3:31][O:32][C:33](=[NH:35])[NH2:34].C([O-])(O)=O.[Na+]>CN(C=O)C>[F:23][C:21]1[CH:22]=[C:17]([CH:16]2[NH:35][C:33]([O:32][CH3:31])=[N:34][C:1]([CH2:2][CH3:3])=[C:5]2[C:6]([O:8][CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[O:7])[CH:18]=[CH:19][C:20]=1[F:24]

Participants

Conditions

Temperature: 70 °C

Procedure

A suspension of benzyl 2-propionyl-3-(3,4,5-trifluorophenyl)-2-propenoate (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 20h. After cooling to room temperature, the reaction 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 afford benzyl 6-(3,4-difluorophenyl)-4-ethyl-2-methoxy-1,6-dihydro-5-pyrimidinecarboxylate as a colorless oil (10.6 g, 58% yield). The product was directly used in the next step after 1H NMR spectroscopy which showed it to be a mixture of amine/imine tautomers.

Workup

temperatureAfter cooling to room temperature
filtrationthe reaction 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-e6138c5f009940e48391561315fd5f8b
Source dataset: uspto-grants-2004_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06720324B2

Reaction notes

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