2,4-Dichloro-5,6-dimethylpyrimidine

5, 6-Dimethyl-1H-pyrimidin-2, 4-dione (2.5 g, 17.8 mmol) was dissolved in 12 mL of phophorus oxychloride, andthe mixture was stirred for 4 hours under reflux. The reaction solution was cooled to at room temperature and added tocold water. The formed precipitate was dried to obtain the title compound (3.08 g, 98 percent).1H-NMR (DMSO-d6) δ 2.51 (3H, s), 2.30 (3H, s)2, 4-Dichloro-5, 6-dimethylpyrimidine (RJ1-008) (WO2013/123401): A mixture of RJ1-006 (4.00 g, 28.5 mmol), phosphorus(V) oxychloride (60 mL, 0.642 mol), and dimethylformamide (0.08 mL, 1.03 mmol) was heated to reflux at 110 °C for 23 hours. The reaction mixture was then cooled to ambient temperature and evaporated. Toluene (80 mL) was added to the residue and the resulting mixture was concentrated. Cold water with ice (160 mL) was added to the residue, and the mixture was extracted with chloroform (3 x 60 mL). The combined organic layers were washed with brine (2 x 150 mL), dried over sodium sulfate, filtered, and concentrated to provide RJ1-008 as a pale yellow solid (4.37 g, 87percent). m.p. = 68-70 °C. A mixture of RJ1-006 (4.00 g, 28.5 mmol), phosphorus(V) oxychloride (60 mL, 0.642 mol), and dimethylformamide (0.08 mL, 1.03 mmol) was heated to reflux at 110 °C for 23 hours. The reaction mixture was then cooled to ambient temperature and evaporated. Toluene (80 mL) was added to the residue and the resulting mixture was concentrated. Cold water with ice (160 mL) was added to the residue, and the mixture was extracted with chloroform (3 x 60 mL). The combined organic layers were washed with brine (2 x 150 mL), dried over sodium sulfate, filtered, and concentrated to provide RJ1- 008 as a pale yellow solid (4.37 g, 87percent). m.p. = 68-70 °C. NMR (400 MHz, CDCb) δ 2.55 (s, 3H), 2.34 (s, 3H). LRMS (ESI+) m/z 177.1 (MC1To a stirred solution of 5, 6-dimethylpyrimidine-2, 4(l f, 3H)-dione (10.3 g, 0.07 mol, Step B) in phosphorus(V) oxychloride (150 mL) was added dimethylformamide (0.2 ml). The resulting mixture was refluxed overnight under argon and cooled down to ambient temperature. The resulting mixture was evaporated. Toluene (200 mL) was added to the residue. The resulting mixture was concentrated. Cold water with ice (400 mL) was added to the residue, and the mixture was extracted with chloroform (3 A mixture of 5, 6-dimethylpyrimidine- 2, 4-diol (10 g, 71.36 mmol) in POCl3 (100 ml) was stirred at 100 °C for 6 h under N2. TLC showed the reaction was complete. The reaction was concentrated in vacuo. The crude product was diluted with DCM (100 mL), aq.NaHCO3 (200 mL) was added to adjust pH=8, separated and extracted with DCM (100 mL x 3). The combined organic layers were dried over Na2SO4, and concentrated in vacuo and purified by column (hexane and ethyl acetate) to afford 2, 4-dichloro-5, 6-dimethyl-pyrimidine (13 g, 92.6percent) as a white solid.Step 1 Step 1 Step A: Cyclobutanol (0.45 g, 6.21 mmol) was dissolved in 40 mL of THF and cooled to 0C. NaH (60 wt% in mineraloil, 0.27 g, 6.77 mmol) was added thereto, and the mixture was stirred for 30 minutes. 2, 4-Dichloro-5, 6-dimethyl-pyrimidine(1.0 g, 5.64 mmol) obtained in Step A was dissolved in 15 mL of THF and added thereto. The mixture was stirred atroom temperature for 16 hours. After addition of water, the reaction solution was extracted with EtOAc. The organiclayer was purified by column chromatography to obtain the title compound (0.84 g, 70 %).1H-NMR (CDCl3) delta 5.24 (1H, m), 2.48 (2H, m), 2.40 (3H, s), 2.13 (2H, m), 2.08 (3H, s), 1.84 (1H, m), 1.68 (1H, m)To a stirred solution of

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:120
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes