2-AMINO-5-BROMO-4-METHOXYPYRIMIDINE

Method 14; Synthesis of 5-bromo-4-methoxypyrimidine-2-ylamine; [0255] To a solution of 4-methoxypyrimidine-2-ylamine (1.84 g, 14.7 mmol) in chloroform (600 mL) was added N-bromosuccinimide (2.62 g, 14.7 mmol). After stirring in the dark for 5 hours, the solution was added to CH0265] To a solution of 4-methoxypyrimidine-2-ylamine (1.84 g, 14.7 mmol) in chloroform (600 mL) was added N-bromosuccinimide (2.62 g, 14.7 mmol). After stirring in the dark for 5 hours, the solution was added to CH4-Methoxy-pyrimidin-2-ylamine (1.17g, 9.35mmol) was taken in chloroform (600ml) to which was added N-bromosuccinimide (1.67g, 9.35mmol). After stirring in the dark for 5h, the solution was added to dichloromethane (125ml) and 1N NaOH (65 ml). Upon mixing thoroughly, the layers were separated. The organic layer was separated, washed with saturated sodium chloride solution (75ml), dried over anhydrous sodium sulphate and filtered. The organic solvents were removed under reduced pressure to yield 1.72 (90percent) of 5-bromo-4-methoxy- pyrimidin-2-yl-amine. This material was pure (HPLC and 1 H NMR) and did not need any further purification.Method 14; Synthesis of 5-bromo-4-methoxypyrimidine-2-ylamine; [0255] To a solution of 4-methoxypyrimidine-2-ylamine (1.84 g, 14.7 mmol) in chloroform (600 mL) was added N-bromosuccinimide (2.62 g, 14.7 mmol). After stirring in the dark for 5 hours, the solution was added to CH2Cl2 (200 mL) and IN NaOH(10O mL). Upon mixing, the layers were separated and the organic layer was washed with NaCl(sat) (10O mL), dried over Na2SO4, filtered and concentrated yielding 2.88 g(96%) of 5-bromo-4-methoxypyrimidine-2-ylamine. LCMS (m/z): 204/206 (MH+). 1H NMR (CDCl3): delta 8.10 (s, IH), 4.93 (bs, 2H), 3.96 (s, 3H).0265] To a solution of 4-methoxypyrimidine-2-ylamine (1.84 g, 14.7 mmol) in chloroform (600 mL) was added N-bromosuccinimide (2.62 g, 14.7 mmol). After stirring in the dark for 5 hours, the solution was added to CH2Cl2 (200 mL) and IN NaOH (100 mL). Upon mixing, the layers were separated and the organic layer was washed with NaCl(sat) (100 rnL), dried over Na2SO4, filtered and concentrated yielding 2.88 g (96%) of 5-bromo-4-methoxypyrimidine-2-ylamine. LCMS (m/z): 204/206 (MH+). 1H NMR(CDCl3): delta 8.10 (s, IH), 4.93 (bs, 2H), 3.96 (s, 3H).4-Methoxy-pyrimidin-2-ylamine (1.17g, 9.35mmol) was taken in chloroform (600ml) to which was added N-bromosuccinimide (1.67g, 9.35mmol). After stirring in the dark for 5h, the solution was added to dichloromethane (125ml) and 1N NaOH (65 ml). Upon mixing thoroughly, the layers were separated. The organic layer was separated, washed with saturated sodium chloride solution (75ml), dried over anhydrous sodium sulphate and filtered. The organic solvents were removed under reduced pressure to yield 1.72 (90%) of 5-bromo-4-methoxy- pyrimidin-2-yl-amine. This material was pure (HPLC and 1 H NMR) and did not need any further purification.General procedure: Compound 1-4 (275 mg, 1.23 mmol) was placed in a sealed tube, and an ammonia-saturated ethanol solution (20 mL) was added and stirred at 100 C for 24 h. Cooled to room temperature, and the solvent was recovered under reduced pressure to give a residue. Purification by silica gel column chromatography using PE: EtOAc (2: 1) as eluent gave a white solid. Yield: 78%;General procedure: N-bromosuccinimide (6.0 g, 34 mmol) was added to a solution of 1a-1 (5.0 g, 30 mmol) in trichloromethane (100 ml) and the mixture was stirred at room temperature for 2 hours. The reaction was complete and the mixture was concentrated under reduced pressure and extracted with dichloromethane. The organic phase was separated and concentrated under reduced pressure to give crude product which was purified by Combi-flash column chromatography to obtain compound 1a-2 (6.0g). Purity: 80%, spectrum data: MS m/z(ESI): 241[M+H]+.To a solution of General procedure: To a solution of appropriate arylamine (5.0 mmol) in dioxane(5 mL) was added NH3*H2O (5 mL) in sealed tube. The reactionmixturewas stirred at 160 C for 3 h. Then the solvent was removedby evaporation, the residue obtained was purified by columnchromatography (eluent gradient 20-30% petroleum ether inEtOAc), gave 51, 53.To a solution of

Molecular Weight:204.02
XLogP3:0.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:202.96942
Monoisotopic Mass:202.96942
Topological Polar Surface Area:61
Heavy Atom Count:10
Complexity:113
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes