3-Methoxypropylamine → 2-{4-[N-(3-Methoxypropyl)sulphamoyl]anilino}-4-(1-methylimidazol-5-yl)pyrimidine

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Reaction Conditions

Reaction Steps

Chlorosulphonic acid (0.22 ml, 3.18 mmol) was added to suspension of 2-anilino-4-(1-methylimidazol-5-yl)pyrimidine (Example 14; 200 mg, 0.80 mmol) in thionyl chloride (4 ml) cooled at 0° C. The mixture was allowed to warm to ambient temperature, stirred for 15 minutes then heated at reflux for 20 minutes. The volatiles were removed by evaporation and the solid residue dried under high vacuum. The residue was suspended in pyridine (3 ml), cooled to −20° C. and diisopropylethyl amine (0.56 ml, 3.98 mmol) followed by 3-methoxypropyl amine (0.16 ml, 1.60 mmol) was added. The reaction mixture was allowed to warm to ambient temperature and stirred for 30 minutes. EtOAc (15 ml) was added and the mixture washed with saturated aqueous sodium hydrogen carbonate solution (15 ml) and then brine (15 ml). The solvent was removed by evaporation and the residue purified by column chromatography eluting with DCM and 2M methanolic ammonia solution (100:0 increasing in polarity to 85:15) to give the title compound 89 mg, (28%) as a solid product. NMR: 1.75 (m, 2H), 2.76 (q, 2H), 3.14 (s, 3H), 3.22-3.30 (m, 2H), 4.01 (s, 3H), 7.25 (d, 1H), 7.34 (t, 1H), 7.70 (d, 2H), 7.77 (s, 1H), 7.83 (s, 1H), 7.91 (d, 2H), 8.47 (d, 1H), 9.92 (s, 1H); m/z 4.03.

Provenance & Evidence