2,4-DIAMINO-6-ETHOXYPYRIMIDINE

To a solution of NaH (2.77 g, 69.2 mmol) in ethanol (150 ml) was added 2, 6-diamino-4-chloropyrimidine (5.0 g, 34.6 mmol). The mixture was refluxed for 6 h. After cooling, the solution was neutralized with a 5-6 N HCl solution in isopropyl alcohol. After removing the solvents in vacuo, the residue was purified by chromatography on silica gel (CHEXAMPLE 54 174 mg of sodium hydride (60percent in mineral oil, 4.36 mmol) are added in portions under an argon atmosphere to a vigorously stirred solution of 500 mg (3.96 mmol) of 2, 6-diaminopyrimidin-4-ol in 10 ml of DMF. After 30 min, 700 μl (5.15 mmol) of ethyl trifluoromethanesulfonate are added dropwise, and the solution is stirred for a further 20 min. To a solution of NaH (2.77 g, 69.2 mmol) in ethanol (150 ml) was added 2, 6-diamino-4-chloropyrimidine (5.0 g, 34.6 mmol). The mixture was refluxed for 6 h. After cooling, the solution was neutralized with a 5-6 N HCl solution in isopropyl alcohol. After removing the solvents in vacuo, the residue was purified by chromatography on silica gel (CH2Cl2/MeOH 40:1), yielding the title compound as a white solid (4.0 g, 75%). Mp 164-165 C. 1H NMR (300 MHz, DMSO, 25 C): delta = 6.00 (s, 2H, NH2), 5.88 (s, 2H, NH2), 5.03 (s, 1H, CH), 4.13 (q, J = 7.1 Hz, 2H, CH2), 1.22 (t, J = 7.1 Hz, 3H, CH3) ppm. 13C NMR (75 MHz, DMSO, 25 C): delta = 170.0, 165.9, 162.9, 76.1, 60.2, 14.7 ppm. HRMS: calcd for C6H11N4O [M+H]+ 155.09329, found 155.09260.EXAMPLE 54 Synthesis of General procedure: A solution of 6-morpholinopyrimidine-2, 4-diamine 1a (5.0 g, 25.6 mmol) and potassium thiocyanate (14.9 g, 0.15 mol) in DMF (120 ml) was heated at 65 C. Pyridine (4.14 ml, 51.2 mmol) was added and the solution cooled to 5 C. Bromine (1.31 ml, 25.6 mmol) was added slowly and the reaction mixture stirred for 2 h at 5-10 C. The reaction mixture was poured into ice-water (100 ml) and stirred for 1 h. The volatiles were removed under reduced pressure and the resulting solid was diluted with water, filtered and dried. The crude solid was purified by flash chromatography on silica gel (CH2Cl2/MeOH 30:1) to yield the title compound as white solid (3.61 g, 56%).270 mg (1 mmol) of 3-[(2-methyl-4-oxo-4H-chromen-8-yl)methylene]pentane-2, 4-dione and 170 mg (1.1 mmol) of 174 mg of sodium hydride (60% in mineral oil, 4.36 mmol) are added in portions under an argon atmosphere to a vigorously stirred solution of 500 mg (3.96 mmol) of 2, 6-diaminopyrimidin-4-ol in 10 ml of DMF. After 30 min, 700 mul (5.15 mmol) of ethyl trifluoromethanesulfonate are added dropwise, and the solution is stirred for a further 20 min. Methanol (1 ml) is then added to the reaction mixture, which is directly purified by preparative HPLC. Combining the product fractions and removing the solvent result in 370 mg (64% of theory) of the title compound as a white solid. LC-MS (method 5): Rt=2.24 min; MS (ESIpos): m/z=155 [M+H]+ 1H-NMR (400 MHz, DMSO-d6): delta=1.21 (t, 3H), 4.12 (q, 2H), 5.00 (s, 1H), 5.87 (s, 2H), 6.01 (s, 2H).

Molecular Weight:154.17
XLogP3:0.2
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:2
Exact Mass:154.08546096
Monoisotopic Mass:154.08546096
Topological Polar Surface Area:87
Heavy Atom Count:11
Complexity:121
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes