4,6-Dichloro-2,5-Dimethyl Pyrimidine

A mixture of 3.3 g (23.5 mmoles) of 2, 5-dimethyl-4, 6-dihydroxy-pyrimidine and 15 ml of phosphorus oxychloride, is taken to reflux for 8 hours. 4, 6-Dichloro-2, 5-dimethylpyrimidine (212 mg, 1.20 mmol) and 3-(piperidin-4- yloxy)benzonitrile hydrochloride (239 mg, 1.0 mmol) were suspended in dioxane (5 mL). (0672) DIPEA (873 mu, 5.00 mmol) and the reaction was stirred at RT for 6 h and then 50 °C for 15 h. (0673) The reaction was cooled to RT and was partitioned between ethyl acetate and aqueous ammonium chloride (staturated). The organics were washed with brine, then dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The residue was purified by silica gel chromatography (0-50percent EtOAc/ hexanes) to afford the title compound. MS: 343 (M+l).A mixture of 4, 6-Dichloro-2, 5-dimethylpyrimidine (2.12 g, 12 mmol) and 2-methoxy-5- (piperidin-4-yloxy)pyridine hydrochloride (2.45 g, 10 mmol) were suspended in 1, 4-dioxane (50 mL). DIPEA (8.73 mL, 50 mmol) was added to the mixture and the reaction was stirred at 60 °C for 15 h. The reaction was cooled to RT and partitioned between ethyl acetate and aqueous NH4C1 (saturated). The organic was washed a second time with aqueous NH4C1, then with brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (15-50percent EtOAc/ hexanes) to afford the title compound. MS: 349 (M+l). XH NMR (500 MHz, CD3OD): delta 7.94 (d, 1 H), 7.69 (dd, 1 H), 7.02 (d, 1 H), 4.66 (m, 1 H), 3.96 (s, m, 5 H), 3.75 (m, 2 H), 2.51 (s, 3 H), 2.33 (s, 3 H), 2.12 (m, 2 H), 1.93 (m, 2 H).

Molecular Weight:177.03
XLogP3:2.9
Hydrogen Bond Acceptor Count:2
Exact Mass:175.9908036
Monoisotopic Mass:175.9908036
Topological Polar Surface Area:25.8
Heavy Atom Count:10
Complexity:108
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes