Carbamimidic acid, methyl ester, sulfate (1:1) → 1,4-Dihydro-2-methoxy-6-methyl-4-(3-nitrophenyl)-5-pyrimidinecarboxylic acid, ethyl ester

HRID 1722405Notes

Reaction equation

[N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([C:17](=O)[CH3:18])[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].[CH3:20][O:21][C:22]([NH2:24])=[NH:23].OS(O)(=O)=O.C(=O)(O)[O-].[Na+]>CN(C)C=O.O>[CH3:20][O:21][C:22]1[NH:24][C:17]([CH3:18])=[C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:10]([C:6]2[CH:7]=[CH:8][CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)[N:23]=1

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of 2-[(3-nitrophenyl)methylene]-3-oxobutanoic acid, ethyl ester (16.46 g, 62.6 mmol), o-methylisourea hydrogen sulfate (14.00 g, 81.4 mmol), and sodium bicarbonate (15.8 g, 18.8 mmol) in dimethylformamide (9.4 ml) was heated at 70° C. (oil bath) under argon overnight. The cooled reaction was diluted with water and extracted with ethyl acetate. The organic phase was washed several times with water, washed with saturated sodium chloride, dried (potassium carbonate) and evaporated. The residue was passed through a pad of silica gel, crystallized from isopropyl ether/hexanes and then triturated with 60% isopropyl ether hexanes (50 ml) to give 1,4-dihydro-2-methoxy-6-methyl-4-(3-nitrophenyl)-5-pyrimidinecarboxylic acid, ethyl ester as light yellow crystals (12.32 g), melting point 101°-103° C.

Workup

customThe cooled reaction
extractionextracted with ethyl acetate
washThe organic phase was washed several times with water
washwashed with saturated sodium chloride
dry with materialdried (potassium carbonate)
customevaporated
customcrystallized from isopropyl ether/hexanes
customtriturated with 60% isopropyl ether hexanes (50 ml)

Sources & evidence

ORD record: ord-257e0764e31c455cb1d0026f6434a4c1
Source dataset: uspto-grants-1989_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04855301

Reaction notes

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