4-CHLORO-5-METHOXY-2-(METHYLSULFANYL)PYRIMIDINE

White solid

A round bottom flask containing ethyl formate (6 mL, 0.062 mol) and ethyl ether (30 mL) was placed in an ice water bath, Na (1.4 g, 0.062 mol) was added under stirring, and then methyl 2-methoxyacetate (6.5 g, 0.062 mol) was added dropwise. The mixture was stirred at room temperaturefor 4 h. The reaction was quenched by addition of ice water (25 mL), and the aqueous phase was separated. To the water layer, S-methyl isothiourea (5.6 g, 0.062 mol) and KOH (2.2 g, 0.062 mol) were added within 40 min, and then heated to 65 °C for 1 h. After cooling, the reaction mixture was neutralized with 37percent HCl. The crude product was collected by vacuum filtration, and then recrystallized with 95percent ethanol to afford 2 as a white needle crystal (4.3 g, 40.1percent yield). m.p. 193-195 °C.The intermediate 2 (1.7 g, 0.01 mol) was added slowly into POCl3 (4.6 g, 0.03 mol) in ice-water bath, and then the mixture was heated to 80 °C for 1 h until the reaction was completed. The reaction mixture was cooled to room temperature and neutralized with 25percent ammonia water. The precipitated solid was filtered and recrystallized with petroleum ether, decolorized by activated carbon. The intermediate 3 was obtained as a light yellow solid (1.8 g, 95.2percent yield). m.p. 74-75 °C. The intermediate 3 was dissolved in methanol (10 mL), 50percent hydrated hydrazine solution (1.6 g, 0.015 mol) was added dropwise in an ice-water bath. Then the mixture was heated to 50 °C and monitored by TLC until the reaction was finished. After cooling, the solvent was removed under reduced pressure, and the solid was recrystallized from ethyl acetate and petroleum ether to afford 5-methoxy-2-(methylthio) pyrimidin-4-yl hydrazine (4, 1.1 g, 96.2percentyield). m.p. 112-114 °C.4-Chloro-5-methoxy-2-methylsulfanyl-pyrimidine4-Chloro-5-methoxy-2-methylsulfanyl-pyrimidine A solution of 5-methoxy-2-methylsulfanyl-3H-pyrimidin-4-one (0.77 g, 4.4 mmol) and POCl3 (6.8 g, 44 mmol) in N, N-dimethyl aniline (0.4 ml) was heated under reflux for 1 h. The reaction mixture was poured into ice (50 ml) and basified to pH 8-9 with saturated aqueous NaHCO3 and the aqueous phase was extracted with DCM (*3). The combined organic phases were dried (Na2SO4) and concentrated in vacuo. The crude residue was purified by column chromatography with EtOAc/hexane (1:9-4:6) as the eluent to give the title compound (0.2 g, 33%).

Molecular Weight:190.65
XLogP3:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:189.9967617
Monoisotopic Mass:189.9967617
Topological Polar Surface Area:60.3
Heavy Atom Count:11
Complexity:127
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes