2-Chloro-4-methoxypyrimidine

To a solution of 2, 4-dichloropyrimidine (41.8 g, 280 mmol) in methanol (900 mL)was added a solution of CH3ONa (15.2 g, 280 mmol) in 100 mL methanol at 0 °C. The mixturewas stirred at rt for overnight. The mixture was concentrated under reduce pressure to give awhite solid, which was diluted with water (400mL) and extracted with ethyl acetate (500 mL x3). The combined organic layer was washed with brine, dried, concentrated to give 2-chloro-4-methoxypyrimidine (40 g, yield: 98percent) as white solid. ESI-MS (M+H): 145.0. ‘H NMR (400 MHz, CDC13) (5: 8.30 (d, J= 5.6 Hz , 1H), 6.68 (s, J= 5.6 Hz , 1H), 4.02 (s, 3H).To a solution of 2, 4-dichloropyrimidine (7.5 g, 50 mmol, ) in MeOH (80 mL) was added dropwise into a solution of NaOMe (2.84 g, 52.5 mmol) in MeOH (20 mL) at 0 °C. The reaction mixture was stirred at 0 °C for 2 h. The reaction mixture was concentrated in vacuo to give crude product. The crude product was poured into 150 mL of water. The aqueous phase was extracted with EtOAc (100 mL). The organic layer was dried with NaPreparative Preparation of 2-chloro-4-methoxypyrimidine [0079] To a solution of 2, 4-dichloro pyrimidine (20 gm) in methanol (200 ml) was added sodium methoxide (8.7 gm) at 0 to 5° C. The resulting mixture was stirred for 14 hours at room temperature and then concentrated under reduced pressure to obtain a residual mass. The residual mass obtained was extracted with ethyl acetate and water. The combined organic layers were washed with water and sodium chloride solution, and then concentrated under vacuum to obtain a crude solid. The crude solid obtained was dissolved in hexane (40 ml) at 0 to 5° C. and stirred for 1 hour. The solid obtained was collected by filtration and then dried to obtain 9.7 gm of 2-chloro-4-methoxypyrimidine.Step-II: To a well stirred solution of 2, 4-dichloropyrimidine 5 (15 g, 0.1 mol, 1 equiv) in 35 ml of MeOH was added 70 ml of MeOH containingMeONa (2.3 g, 0.1 mol, 1 equiv) at 0 C. Then, the reactionmixture was stirred at room temperature for overnight. After removalof the solvent under reduced pressure, appropriate amountof water was added, and then extracted with ethyl acetate(3 30 ml). The organic phase was dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure to give crude product(6) as a white-yellow powder, which was pure enough to beused in the next step. Yield: 85percent, Mp: 53–55 C, 1H NMR(400 MHz, DMSO-d6) d ppm: 3.94 (s, 3H, –OCH3), 7.01 (d, 1H, J = 5.7 Hz, Pyrm-H), 8.46 (d, 1H, J = 5.7 Hz, Pyrm-H); ESI-MS:145.1 [M+H]+, 147.1[M+3]+. C5H5ClN2O [144.56].A solution of 2, 4-dichloropyrimidine (30 g, 0.201 mol) was dissolved in methanol (300 mL) at 0 & lt; 0 & gt; C under stirred conditions, Potassium potassium methoxide (13 g, 0.24 mol) was added and the reaction was allowed to warm to room temperature and stirred overnight. Add appropriate amount of water, extracted with dichloromethane 3 times, The organic phase was combined and washed with saturated brine. The organic phase was dried and the crude dichloromethane was distilled off to give the crude product. N-hexane was added and stirred at 0 ° C for 1 hour to give 16.5 g of compound 2 in 57percent yield.To a solution of 2, 4-dichloro pyrimidine (20 gm) in methanol (200 ml) was added sodium methoxide (8.7 gm) at 0 to 5°C. The resulting mixture was stirred for 14 hours at room temperature and then concentrated under reduced pressure to obtain a residual mass. The residual mass obtained was extracted with ethyl acetate and water. The combined organic layers were washed with water and sodium chloride solution, and then concentrated under vacuum to obtain a crude solid. The crude solid obtained was dissolved in hexane (40 ml) at 0 to 5°C and stirred for 1 hour. The solid obtained was collected by filtration and then dried to obtain 9.7 gm of 2-chloro-4-methoxypyrimidine.[0170j To a solution of 2, 4-dichloropyrimidine (41.8 g, 280 mmol) in methanol (900 mL)was added a solution of CH3ONa (15.2 g, 280 mmol) in 100 mL methanol at 0 C. The mixturewas stirred at rt for overnight. The mixture was concentrated under reduce pressure to give awhite solid, which was diluted with water (400mL) and extracted with ethyl acetate (500 mL x3). The combined organic layer was washed with brine, dried, concentrated to give To a solution of 2, 4-dichloropyrimidine (7.5 g, 50 mmol, ) in MeOH (80 mL) was added dropwise into a solution of NaOMe (2.84 g, 52.5 mmol) in MeOH (20 mL) at 0 C. The reaction mixture was stirred at 0 C for 2 h. The reaction mixture was concentrated in vacuo to give crude product. The crude product was poured into 150 mL of water. The aqueous phase was extracted with EtOAc (100 mL). The organic layer was dried with Na2SO4and concentrated in vacuum to give Example 1.1.25: (4-methoxypyrimidin-2-yl)methanamine; To the 2, 4-dichloropyrimidine (1 g, 6.71 mmol) in MeOH (11 mL), NaOMe (362 mg, 6.71 mmol) was added and the reaction mixture was stirred at rt for 0.5 h. Then 15 mL of (1) 2, 4-Dichloropyrimidine (5.0 g) was dissolved in methanol (15 ml), a 28% solution of sodium methoxide in methanol (6.7 ml) was added dropwise to the solution under ice cooling, and the resulting mixture was stirred overnight at room temperature. A 28% solution of sodium methoxide in methanol (3 ml) was further added dropwise to the reaction mixture at room temperature, and the resulting mixture was stirred for 6 hours. Distilled water was added to the reaction mixture, the resulting mixture was extracted with ethyl acetate, and the organic layer was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate = 5:1 to 2:1) to obtain a methoxy compound (329 mg).

Molecular Weight:144.56
XLogP3:1.5
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:144.0090405
Monoisotopic Mass:144.0090405
Topological Polar Surface Area:35
Heavy Atom Count:9
Complexity:91
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes