2-METHOXY-PYRIMIDINE-5-CARBALDEHYDE

(A) To a solution of 2-bromoacetic acid (40 g, 289.55 mmol, 1 eq) in DMF (125 ml) was added POCI3(106 ml) dropwise at 0°C and the RM was stirred at 105°C for 8 h. The RM was quenched with EtCH(160 ml) dropwise at 0°C, followed by THF (800 ml). The RM was stirred at 0°C for 2 h. The precipitatedcrystals were filtered off, washed with (20percent EtOH-THF) and dried under vacuum.(B) To a solution of methyl carbamimidate sulfate (10 g, 81.3 mmol, 1 eq) and the product from step (A)(41.30 g, 162.6 mmol, 2 eq) in ‘PrOAc (200 ml) was added a solution of KHCO3 (24.39 g, 243.9 mmol, 3eq) in water (100 ml) in one portion at RT. The RM was stirred at RT for 48 h. It was diluted with water (100 ml) and the aq. layer was extracted with EtOAc (3x 100 ml). The organics were dried (Na2SO4) and concentrated to afford 2-methoxypyrimidine-5-carbaldehyde (10 g, 88percent; over 2 steps).To a solution of intermediate 3 (0.50 g, 0.24 mmol) in anhydrous DCM (1 mL), 2- methoxypyrimidine-5-carbaldehyde (CAS 90905-32-1, 0.05 g, 0.36 mmol) and titanium(IV)isopropoxide (0.10 mL, 0.36 mmol) were added and the reaction mixture was stirred at rt for 24 h. Then the reaction was cooled to 0 C and a 1 4M solution of methylmagnesium bromide in THFdoluene (0.87 mL, 1.22 mmol) was added dropwise and the reaction mixture was stirred at 0 C for 5 min and at rt for 3.5 h. Then saturated solution of NH4Cl was added and the product extracted with DCM. The organic layer was separated, dried (MgS04), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; 7M solution of ammonia in MeOH in DCM 0/100 to 2/98). The desired fractions were collected and the solvents evaporated in vacuo. The desired fractions were collected and the solvents evaporated in vacuo. The resulting mixture was purified by RP HPLC (Stationary phase: C18 XBridge 30 x 100 mm 5 pm, mobile phase: Gradient from 75% NH4HC03 0.25% solution in H20, 25% CH3CN to 57% NH4HC03 0.25% solution in H20, 43% CH3CN). The desired fractions were collected and the solvents evaporated in vacuo to yield product 65 (37 mg, 44%) as a yellow oil.To the round bottom flask was added 5.0 g of 2-methoxy-5-aldehyde pyrimidine dissolved in 25 ml of acetic acid.Further, 4.67 g of hydrobromic acid was added, and the mixture was heated to 60 C for 5 hours, and the reaction of the starting material by TLC was completed. After the reaction system is cooled to room temperature, Dry acetic acid with toluene, and make the product salt with aqueous sodium bicarbonate solution.It was extracted with ethyl acetate to remove fat-soluble impurities and repeated twice.The product was freed by the addition of 1 M hydrochloric acid and evaporated to dryness.It was purified by acetonitrile, and the solid was precipitated and suction filtered.3.95 g of 2-hydroxy-5-aldehyde pyrimidine, a compound of formula I, was obtained in a yield of 88%.

Molecular Weight:138.12
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:138.042927438
Monoisotopic Mass:138.042927438
Topological Polar Surface Area:52.1
Heavy Atom Count:10
Complexity:110
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes