5-BROMO-2-CHLORO-4-METHOXYPYRIMIDINE

A 30percent solution of sodium methoxide in methanol (8.0 mL, 42.0 mmol) was added dropwise to a cooled (ice-bath) solution of 5-bromo-2, 4-dichloropyrimidine (9.85 g, 43.2 mmol) in methanol (100 mL). The mixture was warmed to room temperature and stirred for 4 hours. The solvent was removed under reduced pressure and the residue was partitioned between water and dichloromethane. The organic layer was washed with water, brine, dried (MgS0  sodium methoxide in methanol (8.0 mL, 42.0 mmol) was added dropwise to a cooled (ice-bath) solution of 5-bromo-2, 4-dichloropyrimidine (9.85 g, 43.2 mmol) in methanol (100 mL). The mixture was warmed to room temperature and stirred for 4 hours. The solvent was removed under reduced pressure and the residue was partitioned between water and dichloromethane. The organic layer was washed with water, brine, dried (MgSO5-bromo-2, 4-dichloropyrimidine (500mg, 2.194mmol) was dissolved in anhydrous methanol (5mL) in, under nitrogen, was added dropwise sodium methoxide (sodium 56mg, 2.42mmol) in methanol (1.85 mL) And stirred overnight at room temperature. Saturated ammonium chloride solution was added to quench the reaction, recovery of the solvent under reduced pressure, added to the washed CH2Cl2 (30mL), washed with water (30 mL) under reduced pressure to recover the solvent. Purification by silica gel column chromatography eluting with PE: EtOAc (4: 1) gave a white solid. Yield: 90percent;To a stirred solution of 5-bromo-2, 4-dichloropyrimidine (500 mg, 2.19 mmol) in MeOH (5 mL) was added a 30percent solution of sodium methoxide (0.40 mL, 2.26 mmol). The reaction mixture was stirred at RT for 2 h then concentrated. The residue was dissolved in water (5 mL) and extracted with EA (3 x 5 mL). The combined organic layer was washed with brine, dried over MgS0[006451 To a stined solution of 5-bromo-2, 4-dichloropyrimidine (500 mg, 2.19 mmol) in MeOH (5 mL) was added a 30percent solution of sodium methoxide (0.40 mL, 2.26 rnrnol). The reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was dissolved in water (5 mL) and extracted with EA (3 x 5 mL). The combined organic layer was washed with brine, dried over MgSO4 and concentrated to afford 432 mg (88percent) of 5-brorno-2-chloro-4-rnethoxypyrimidine as white solid. LCMS-ESI (rnIz) calculated for C5H4BrCIN7O: 223.4; found 224.2 [M+H], 1R = 7.66 mm. (Method 2).Intermediate 26: 5-Bromo-2-chloro-4-(methyloxy)pyrimidineTo a solution of 5-bromo-2, 4-dichloropyrimidine (17.82 g, 78.2 mmol) in methanol (100 mL) stirred at 0 °C was added solid sodium methoxide (4.22 g, 78 mmol) portionwise during 5 minutes. The reaction mixture was stirred at 23 °C overnight. To the organic phase was added water (25 mL) and the methanol was removed. Then it was extracted with dichloromethane. The organic phase was dried over sodium sulphate and evaporated in vacuo to give the title compound as a white solid (17.2 g, 67.6 mmol, 86 percent yield). LC/MS [M+H]To a cooled (-78 °C) solution of 5-bromo-2, 4-dichloropyrimidine (1.7 g, 7.3 mmol) in THF (30mL) was added dropwise a 25 wtpercent solution of methylamine in ethanol (1.7 mL). The reaction was allowed to warm to 0 °C and stirred for 1 h. The reaction was then concentrated and re-dissolved in EtOAc. The solution was washed with brine, dried over NaGeneral procedure: To a 250 mL round bottom flask equipped with a stir bar was added 1 g 5- chloro-2, 4-dichloro- pyrimidine, and 15mL of diethyl ether. The mixture was cooled to 0C in an ice bath and then 1 equivalent of sodium methoxide in methanol (prepared from reacting 120 mg of sodium with 4 mL of methanol at room temperature) was slowly added. The reaction was stirred over night at room temperature and checked by LCMS. The white precipitate was filtered and the solid washed with cold methanol. After drying, 0.98 g of pure 2, 5-dichloro-4- methoxypyrimidine was obtained and this material was used without further purification.A mixture of A mixture of Step 2: Preparation of l-(4-(2-chloro-4-methoxypyrimidin-5-yl)phenyl)pynOlidin-2-one. [0834] l-(4-(4, 4, 5, 5-tetramethyl-l, 3, 2-dioxaborolan-2-yl)phenyl)pyrrolidin-2-one (1.41 g, 4.92 mmol),

Molecular Weight:223.45
XLogP3:2.2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:221.91955
Monoisotopic Mass:221.91955
Topological Polar Surface Area:35
Heavy Atom Count:10
Complexity:116
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes