4-AMINO-6-PHENYLPYRIMIDINE

General procedure: To a solution of isoquinolin-3-amine (1.00 g, 6.94 mmol) in THF (20 mL) was added sodium hydride (0.555 g, 13.9 mmol) at 0 C under nitrogen. The mixture was allowed to warm to room temperature over 1 h. Carbon disulfide(1.00 mL, 16.7 mmol) was then added and the mixture was heated at 70 C for 20 h. The reaction mixture was cooled to 0 C and sodium hydride (0.555 g, 13.9 mmol) was added. The reaction mixture was stirred for 30 min at 0 C, followed by the addition of iodomethane (1.04 mL, 16.7 mmol). Stirring was continued at room temperature for 18 h. The reaction mixture was poured into water and filtered. The filtrate was concentrated and purified by flash chromatography on silica gel (0-20% ethyl acetate in hexanes). Product fractions were combined and concentrated in vacuo to give dimethyl isoquinolin-3-ylcarbonimidodithioate (0.64 g, 37 %) as a yellow solid.Quinoline-4-carboxylic acid (36.4 mg, 0.226 mmol), 3-chloro-5 - (methylthio) benzene amine (50.0 mg, 0.205 mmol) and POCl3 (34.6 mg, 0.226 mmol), pyridine (1 mL) was dissolved in, 80 was stirred for 1 hour dongan. When thin layer chromatography (TLC) check when, a new spot is confirmed, water was added to the reaction mixture, and extracted twice with dichloromethane. And the extracted organic layer was dried using magnesium sulfate, vacuum concentrated and, after the water was removed by filtration of the organic extract over MgSO4 and concentrated by silica gel preparative thin layer chromatography (preparative TLC, ethyl acetate / n- hexane = l / l ) to give to give the title compound (11%) of a white solid.General procedure: Quinoline-4-carboxylic acid (36.4 mg, 0.226 mmol), 3-chloro-5 - (methylthio) benzene amine (50.0 mg, 0.205 mmol) and POCl3 (34.6 mg, 0.226 mmol), pyridine (1 mL) was dissolved in, 80 was stirred for 1 hour dongan. When thin layer chromatography (TLC) check when, a new spot is confirmed, water was added to the reaction mixture, and extracted twice with dichloromethane. And the extracted organic layer was dried using magnesium sulfate, vacuum concentrated and, after the water was removed by filtration of the organic extract over MgSO4 and concentrated by silica gel preparative thin layer chromatography (preparative TLC, ethyl acetate / n- hexane = l / l ) to give to give the title compound (11%) of a white solid.To a solution of A mixture of 6-chloropyrimidin-4-amine (0.324 g, 2.5 mmol), phenylboronic acid (0.381 g, 3.13 mmol), Na2CO3 (0.795 g, 7.50 mmol) and Bis(triphenylphosphine)palladium(II) chloride (0.035 g, 0.050 mmol) were suspended in a mixture of Dioxane (15 mL)/EtOH (2 mL)/water (3 mL). The mixture was heated a heating block at 125 C for 2 h and concentrated. The residue was purified on the silica gel using 100 % ethyl acetate, then 10% methanol in ethyl acetate. The desired fractions were concentrated to give an off-white solid (0.25 g, 58 %).1H NMR (400 MHz, DMSO-d6) d ppm 8.44 (1 H, d, J=1.26 Hz), 7.93 - 8.00 (2 H, m), 7.42 - 7.52 (3 H, m), 6.91 (2 H, s), 6.88 (1 H, d, J=1.26 Hz). LCMS (method D) tR, 2.58min., MH+ = 172.1.Step A: 6-Phenylpyrimidin-4-amine A mixture of 6-chloropyrimidin-4-amine (0.32 g, 2.5 mmol), phenylboronic acid (0.38 g, 3.13 mmol), saturated aqueous sodium carbonate (0.80 g, 7.50 mmol) and bis(triphenylphosphine)palladium(II) chloride (0.035 g, 0.05 mmol) were suspended in a mixture of dimethoxyethane (15 mL)/ethanol (2 mL)/water (2 mL). The mixture was heated in the microwave at 125 C. for 20 min then concentrated in vacuo. The residue was purified by column chromatography (10-60% ethyl acetate/hexanes) to afford Step A: 6-Phenylpyrimidin-4-amine A mixture of 6-chloropyrimidin-4-amine (0.32 g, 2.5 mmol), phenylboronic acid (0.38 g, 3.13 mmol), saturated aqueous sodium carbonate (0.80 g, 7.50 mmol) and bis(triphenylphosphine)palladium(H) chloride (0.035 g, 0.05 mmol) were suspended in a mixture of dimethoxyethane (15 mL)/ethanol (2 mL)/water (2mL). The mixture was heated in the microwave at 125 C for 20 min then concentrated in vacuo. The residue was purified by column chromatography (10-60 % ethyl acetate/hexanes) to afford A mixture of 6-chloropyrimidin-4-amine (0.32 g, 2.5 mmol), phenylboronic acid (0.38 g, 3.13 mmol), saturatedaqueous sodium carbonate (0.80 g, 7.50 mmol) and bis(triphenylphosphine)palladium(II) chloride (0.035 g, 0.05 mmol)were suspended in a mixture of dimethoxyethane (15 mL)1ethanol (2 mL)/water (2 mL). The mixture was heated in themicrowave at 125 C. for 20 min then concentrated in vacuo.The residue was purified by column chromatography (1060%ethyl acetate/hexanes) to afford 6-phenylpyrimidin-4amine(167 mg, 0.98 mmol, 39% yield) as an off-white solid.

Molecular Weight:171.20
XLogP3:1.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:171.079647300
Monoisotopic Mass:171.079647300
Topological Polar Surface Area:51.8
Heavy Atom Count:13
Complexity:154
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes