N,N-Dimethylaniline → 4-chloro-N-(3-(2-methylthiazol-4-yl)phenyl)pyrimidin-2-amine

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Reaction Steps

To 2-(3-(2-methylthiazol-4-yl)phenylamino)pyrimidin-4(3H)-one, 11, (1.0 g, 3.5 mmol) and N,N-dimethyl-aniline (1 mL) is added phosphorus oxychloride (9.5 mL). The resulting mixture is heated to reflux for 15 minutes, cooled to room temperature and concentrated in vacuo. The residue is neutralized to pH 7 with 1M NaOH (aqueous). The organic layer is extracted with ethyl acetate (3×50 mL). The combined organic layers are dried (MgSO4) and concentrated in vacuo. The residue is purified over silica (5% EtOAc in hexanes) to afford 0.50 g (47% yield) of the desired compound. 1H NMR (DMSO-d6, 300 MHz): δ 2.73 (s, 3H), 6.98 (d, J=5.1 Hz, 1H), 7.37 (t, J=8.1 Hz, 1H), 7.57 (d, J=8.1 Hz, 1H), 7.72 (d, J=8.1 Hz, 1H), 7.83 (s, 1H), 8.25 (s, 1H), 8.46 (d, J=5.1 Hz, 1H), 10.08 (s, 1H). MS (ESI, pos. ion) m/z: 303 (M+1).

Provenance & Evidence