2-Amino-4-pyrimidinemethanol

2-Amino-4-methoxycarbonylpyrimidine (3.0g, 20mmol, Reference Compound No.3-1) was suspended in a mixture solvent of ethanol (150mL) and dichloromethane (20mL), then sodium borohydride (2.2g, 59mmol) was added thereto at room temperature, and the whole was stirred for 24 hours. Hydrochloric acid (2M, 207 mL, 414 mmol) was added to 4-(dimethoxymethyl)pyrimidin-2-amine (68) (WO 2007/096764) (14.0 g, 83 mmol) and the mixture heated at 48° C. for 16 hr. The mixture was cooled to RT and was neutralized with solid NaIntermediate P: 1-(4-((2-Aminopyrimidin-4-yl)methoxy)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureaGeneral procedure: To a solution of aldehyde in the indicated solvent is added sodium borohydride at 0 °C. After stirring at room temperature for 2 hours, water is added and the mixture is concentrated.Following Procedure C using crude 4 (1.0 g, 6.35 mmol), MeOH, and sodium borohy dride (360 mg, 9.55 mmol), then quench with water (1 mL) and purify with silica gel column chromatography (MeOH:DCM := 1 :50) to give AS as a solid (650 mg, 65percent yield). (MS: [M+H]+ 160.1)Hydrochloric acid (2M, 207 mL, 414 mmol) was added to 4-(dimethoxymethyl)pyrimidin-2-amine (68) (WO 2007/096764) (14.0 g, 83 mmol) and the mixture heated at 48° C. for 16 hr. The mixture was cooled to RT and was neutralized with solid Na2CO3 which produced a precipitate at pH 7. The suspension was diluted with EtOAc (300 mL) and the solid removed by filtration. The organic layer was separated and the aqueous layer was extracted with 1percent MeOH in THF (4×300 mL). The organics were combined, dried and then evaporated in vacuo. The residue (ca. 4.0 g) was suspended in a mixture of MeOH (100 mL), THF (100 mL) and water (100 mL) and treated with NaBH4 (1.57 g, 41.4 mmol). After stirring for 1 hr a solution of NaOH (1M, 20 mL) was added and the mixture was allowed to stand at RT for 48 hr. The solvents were evaporated to give a yellow solid which was partitioned between water (50 mL) and EtOAc (100 mL). The solid which formed at the interface was removed by filtration and the aq layer was extracted with THF (3×300 mL) then dried and evaporated to give a yellow solid. The material was suspended in THF (100 mL) and MeOH (50 mL) and absorbed onto silica gel (20 g) and subjected to column chromatography (80 g, 15percent MeOH in DCM isocratic elution) to give The solution of 5.01 g 4-(dimethoxymethyl)pyrimidin-2-amine (29.5 mmol) in 100 mL 2Naq. HCI was stirred at 60°C for 5h. Reaction mixture was cooled to 0°C, then 7.60 g NaOH(190 mmol) was added portionwise. The pH was adjusted to 8 using 10percent K2C03 solution, then 2.24 g sodium borohydride (59.0 mmol) was added portionwise keeping the temperature under 5°C and stirred for 30 mm at 0°C. The reaction mixture was extracted with EtOAc, the combined organic phases were dried over Na2SO4 and concentrated underreduced pressure. The crude product was purified via flash chromatography (MeOH - containing I percentN113- and DCM).?FT NMR (400 MHz, DMSO-d5): 8, 20 (d, 111), 6.66 (d, 111), 6.49 (br s, 211), 5.35 (t, IH), 4.30 (d, 211).

Molecular Weight:125.13
XLogP3:-1
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:125.058911855
Monoisotopic Mass:125.058911855
Topological Polar Surface Area:72
Heavy Atom Count:9
Complexity:88.3
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes