6-chloro-Nmethylpyrimidin-4-amine

Into a 100-mL round-bottom flask, was placed N, N-dimethylformamide (10 mL), 4, 6- dichloropyrimidine (1 g, 6.71 mmol, 1 equiv), CS2COA mixture of 79 (0.50g, 3.36mmol) and IPA (1.5ml) was stirred for a while and then 2M methylamine in THF (4.2ml, 8.40mmol) was added thereto at 0 °C. The resulting mixture was back to room temperature under stirring for overnight. The reaction was quenched by water and then the mixture was extracted by ethyl acetate (30ml x 3). The residue was purified by flash column over silica gel (ethyl acetate: n-Hexane = 1 :2, Rf = 0.20) to afford 83 (0.47g, 97.43percent) as a pale yellow solid. 1H-NMR (300MHz, CDClTo a solution of 4, 6-dichloropyrimidine (0.50 g) in tetrahydrofuran (0.84 mL), triethylamine (0.94 mL) was added, then a 2.0 mol/L solution of methylamine in tetrahydrofuran (1.7 mL) was added dropwise under ice cooling, and themixture was stirred at room temperature for 23 hours. The reaction solution was concentrated, and then, the obtaine dresidue was purified by silica gel column chromatography (MORITEX Purif Pack-NH, chloroform) to obtain the titlecompound (0.45 g, 93percent) as a colorless solid.1H NMR (300 MHz, CDCl3) δ ppm 2.96 (d, J=5.0Hz, 3H), 6.35 (s, 1H), 8.35 (s, 1H). MS (+): 144 [M+H]+.Take 4, 6-dichloropyrimidine (75.7 g, 0.51 mol), Isopropanol (0.98 L) and methylamine/tetrahydrofuran solution (2 mol/L, 0.76 L, 1.52 mol) were added.Stir at room temperature for 15 hours. The reaction was completely monitored by TLC, the reaction mixture was filtered, and the filtrate was concentrated.Distilled water (500 mL) and EA (300 mL) were added, liquid separation, aqueous phase EA extraction (300 mL×2), and the organic phase was combined.Wash with saturated aqueous sodium chloride solution, dry over anhydrous sodium sulfate, Beat with ethyl acetate: petroleum ether (1:30, 800 mL), After drying, a brown solid (68.0 g, yield 93percent) was obtained.General procedure: To a suspension of 4, 6-dichloropyrimidine 53 (3.0 g, 20 mmol) in isopropanol (40 mL) was added appropriate amine at such a rate that the internal temperature did not rise above 40 °C. After completion of the addition, the reaction mixture was stirred for 1 h at 25 °C. Water (30 mL) was added, and the resulting suspensio nwas cooled in an ice bath to 0 °C. The precipitated product was filtered off and washed with cold isopropanol/water (2:1, 50 mL) and water. The collected material was dried in vacuo to afford the title compounds.4, 6-Dichloropyrimidine (10 g, 67 mmol) was dissolved in 100 ml isopropanol and the solution was cooled to 0 00 reprecipitating. Methylamine solution (33percent w/w, 17 ml, 140 mmol) was added slowly with stirring and the mixture was stirred overnight atroom temperature. The mixture was evaporated under reduced pressure. The residue was resuspended in water, stirred for 15 mm and then filtered. The solid was dried under reduced pressure. The filtrate was extracted three times with ethyl acetate. The combined organics were dried over anhydrous sodium sulphate, filtered and evaporated under reduced pressure. The solid obtained was combined with the firstprecipitate to give 8.50 g (59 mmol, 88percent yield) of the title compound as a white solid. Purity 87percent.1H NMR (300 MHz, CHLOROFORM-d) ö ppm 8.40 (s, 1H), 6.38 (s, 1H), 2.98 (d, 3H, J = 5.1 Hz).UPLC/MS (3 mm) retention time 0.74 mm.LRMS: m/z 144 (M+1, ixOl).6-Chloro-N-methylpyrimidin-4-amine (16)[00404] To a solution of 4, 6-dichloropyrimidine (5.0 g, 33.79 mmol) in anhydrous THF (50 mL) was slowly added 2.0 M methylamine solution in THF (42.2 mL, 84.48 mmol) at -40 °C. The reaction mixture was stirred at 0 °C for 4 h and partitioned between CHCl[0174] To a suspension of 4, 6-dichloropyrimidine (0.50 g, 3.4 mmol) in propan-2-ol (10 mL) was added dropwise methylamine (2 M, 3.4 mL). After addition was completed, the reaction mixture was stirred at room temperature for 1 hour. Upon completion, the reaction mixture was concentrated in vacuo. The residue was dissolved with dichloromethane (50 mL), washed with water (10 mL), brine (2x 10 mL) sequentially. The organic phase was collected and concentrated to give 6-chloro-N-methylpyrimidin-4-amine (0.42 g, 86percent yield) as a white solid.Example J cr ^ e. ( 6-Ch loro-pyrimidin~4~yl)~methyl-amine To a solution of 4, 6-dic oro-pyrimidine (7.45 g, 50 mmol) in iPrOH (50 mL) was added a solution of methyl amine in THF (2M, 30 mL, 60 mmol) at room temperature. The resulting mixture was stirred for 18 hours. The mixture was concentrated and the residue was purified by flash chromatography on silica eiuting with DCM:EtOAc = 6:1-1 :1 to obtain the title compound (4.4 g, yield: 62percent) as a white solid. To a solution of 4, 6-dichloro-pyrimidine (7.45 g, 50 mmol) in iPrOH (50 mL) was added a solution of methyl amine in THF (2M, 30 mL, 60 mmol) at room temperature. The resulting mixture was stirred for 18 hours. The mixture was concentrated and the residue was purified by flash chromatography on silica eluting with DCM:EtOAc = 6: 1—1 : 1 to obtain the title compound (4.4 g, yield: 62percent) as a white solid. 1H-NMR (400 MHz, CDC1General procedure: A solution of 4, 6-dichloropyrimidine (20.14 mmol, 3.0 g) (A1) in 20 ml of isopropanol was slowly added dropwise to 10 ml of aqueous ammonia or methylamine or ethylamine at room temperature for 2 h. The solvent was evaporated under reduced pressure, Solid, adding 20 ml of water stirring filter, filter cake washed with water, vacuum drying, in intermediate A2 or A3.4 - methylamino -6 - chloro pyrimidine (A2), the white crystal, yield 62percent.

Molecular Weight:143.57
XLogP3:1.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:143.0250249
Monoisotopic Mass:143.0250249
Topological Polar Surface Area:37.8
Heavy Atom Count:9
Complexity:88.3
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes