Aniline → 3-(4-Chloro-2-phenylamino-pyrimidin-5-yl)-2-(4-methoxy-phenyl)-propionic acid methyl ester

HRID 11792

Reaction equation

[CH3:1][O:2][C:3](=[O:22])[CH:4]([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[CH2:5][C:6]1[C:7]([Cl:13])=[N:8][C:9](Cl)=[N:10][CH:11]=1.[NH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(N(CC)C(C)C)(C)C>C(O)CCC.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:22])[CH:4]([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[CH2:5][C:6]1[C:7]([Cl:13])=[N:8][C:9]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[N:10][CH:11]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 3-(2,4-dichloro-pyrimidin-5-yl)-2-(4-methoxy-phenyl)-propionic acid methyl ester (341 mg, 1.0 mmol) (from Example 1d supra) in n-butanol (10 mL) was added aniline (200 mg, 2.15 mmol) (Aldrich) followed by N,N-diisopropylethylamine (258 mg, 2.0 mmol) (Aldrich) and the reaction mixture was heated at 100° C. for 12 hours. After cooling, the reaction mixture was diluted with ethyl acetate (100 mL) and successively washed with saturated aqueous ammonium chloride solution (30 mL), water (30 mL) and brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography (silica gel) to give 3-(4-chloro-2-phenylamino-pyrimidin-5-yl)-2-(4-methoxy-phenyl)-propionic acid methyl ester. (Yield 45.1 mg, 11.3%).

Workup

temperatureAfter cooling
washsuccessively washed with saturated aqueous ammonium chloride solution (30 mL), water (30 mL) and brine (30 mL)
dry with materialdried over anhydrous sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude product was purified by flash column chromatography (silica gel)

Sources & evidence

ORD record: ord-0fc233a13f9f4025aae8312c9520c8fc
Source dataset: uspto-grants-2006_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07098332B2

Linked notes

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