O-Toluidine → N-(4-hydroxyphenyl)-6-(o-tolylamino)pyrimidine-4-carboxamide

HRID 1946722Notes

Reaction equation

Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([C:8]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][C:12]=2C)=[O:9])[CH:3]=1.ClC1N=CN=C(C(NC2C=CC(O)=CC=2)=O)C=1.C(N(C(C)C)C(C)C)C.[NH2:45][C:46]1[C:47]([CH3:52])=[CH:48][CH:49]=[CH:50][CH:51]=1>C(O)C>[OH:17][C:14]1[CH:13]=[CH:12][C:11]([NH:10][C:8]([C:4]2[CH:3]=[C:2]([NH:45][C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=3[CH3:52])[N:7]=[CH:6][N:5]=2)=[O:9])=[CH:16][CH:15]=1

Participants

Conditions

Temperature: 160 °C

Procedure

A solution of 6-chloro-N-(4-hydroxy-2-methylphenyl)pyrimidine-4-carboxamide, Intermediate 7 (50.0 mg; 0.20 mmol) in ethanol (3 mL) was treated with N-ethyldiisopropylamine (69 μl; 0.4 mmol) and o-toluidine (Fluka, 21.5 μl; 0.20 mmol). The reaction mixture was heated at 160° C. for 3 hours under microwave irradiation. The solvents were removed in vacuo, EtOAc was added and the organic phase was washed with a citric acid solution, dried over magnesium sulfate then evaporated in vacuo. The crude product was purified by column chromatography (silica), eluting with cyclohexane containing an increasing amount of EtOAc. The title compound was obtained as a yellow solid.

Workup

customThe solvents were removed in vacuo, EtOAc
additionwas added
washthe organic phase was washed with a citric acid solution
dry with materialdried over magnesium sulfate
customthen evaporated in vacuo
customThe crude product was purified by column chromatography (silica)
washeluting with cyclohexane containing an increasing amount of EtOAc

Sources & evidence

ORD record: ord-9fea9813494c424b91095330d685074a
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08399448B2

Reaction notes

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