2,6-dichloro-N-Methyl pyriMidin-4-aMine

Intermediate 2; 2, 6-dichloro-λ/-methyl-4-pyrimidinamine ( Intermediate 3 4, 6-dichloro-λ/-methyl-2-pyrimidinamine; To a OA solution of methylamine (57 ml of a 2M solution in THF) was added dropwise to a stirred solution of trichlo50 ropyrimidine (124a; 10.00 g) in anhydrous THF (80 ml) at—20 C, under an atmosphere of nitrogen and the reaction was maintained at this temperature for 0.5 h. The volatiles were removed under reduced pressure and the residue partitionedbetween methylene chloride and 10percent aq. NaOH. Theorganic phase was separated, washed with water, dried(MgSO4), and concentrated under reduced pressure. The residue was purified by silica gel colunm chromatography using EtOAc; hexanes (1:20) as eluent to give the desiredproduct (312i; 4.05 g) as a white solid. The relatively morepolar isomer (312j) was set aside at this time.Intermediate 2; 2, 6-dichloro-lambda/-methyl-4-pyrimidinamine ( Intermediate 3 4, 6-dichloro-lambda/-methyl-2-pyrimidinamine; To a O0C mixture 2, 4, 6-trichloropyrimidine (0.50 g, 2.7 mmol) in THF (3 mL) was added methyl amine (2M THF, 3.0 mL, 6.0 mmol) dropwise. The reaction mixture was warmed to room temperature and stirred for 30 minutes, at which time LCMS indicated the formation of the desired product. The reaction mixture was treated with water (10 mL) and extracted with EtOAc (2x10 mL). The organics were washed with brine (10 mL), dried (Na2SO4), and evacuated. The crude material was purified by column chromatography (Gradient from 0-30% EtOAc in Hexanes) to afford 180 mg (1.01 mmol, 38%) of 2, 6- A solution of methylamine (57 ml of a 2M solution in THF) was added dropwise to a stirred solution of trichlo50 ropyrimidine (124a; 10.00 g) in anhydrous THF (80 ml) at-20 C, under an atmosphere of nitrogen and the reaction was maintained at this temperature for 0.5 h. The volatiles were removed under reduced pressure and the residue partitionedbetween methylene chloride and 10% aq. NaOH. Theorganic phase was separated, washed with water, dried(MgSO4), and concentrated under reduced pressure. The residue was purified by silica gel colunm chromatography using EtOAc; hexanes (1:20) as eluent to give the desiredproduct (312i; 4.05 g) as a white solid. The relatively morepolar isomer (312j) was set aside at this time.A solution of methylamine (57ml of a 2M solution in THF) was added dropwise to a stirred solution of trichloropyrimidine (124a; 10.0Og) in anhydrous THF (80ml) at -20C, under an atmosphere of nitrogen and the reaction was maintained at this temperature for 0.5h. The volatiles were removed under reduced pressure and the residue partitioned between methylene chloride and 10% aq. NaOH. The organic phase was separated, washed with water, dried (MgSO4), and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using EtOAc; hexanes (1 :20) as eluent to give the desired product (312; 4.05g) as a white solid. The relatively more polar isomer (312j) was set aside at this time.To a mixture of N-(4, 6-dichloro-pyrimidin-2-yl)-2, 2, 2-trifluoro-acetamide (4.6 g, 17.7 mmol) and potassium carbonate (4.9 g, 35.4 mmol) in acetone (100 ml) was added iodomethane (1.3 ml, 21.2 mmol). After stirring for 12 hours, the mixture was filtered through a pad of celite under suction. The filtrate was concentrated under reduced pressure and the residue was treated with methanol (150 ml) tetrahydrofuran (30 ml), and a solution of potassium carbonate (5.0 g, 51 mmol) in water (15 ml). After stirring for 1 hour, the mixture was concentrated under reduced pressure. The residue was partitioned between ethyl acetate (150 ml) and saturated aqueous sodium chloride solution (100 ml). The organic phase was dried over magnesium sulfate. After evaporation of the solvent under reduced pressure, the residue was purified by flash chromatography eluding with ethyl acetate-hexane (1:6 followed by 1:4) to give N-Preparation of the

Molecular Weight:178.02
XLogP3:2.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:176.9860526
Monoisotopic Mass:176.9860526
Topological Polar Surface Area:37.8
Heavy Atom Count:10
Complexity:101
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes