4-Amino-5-bromo-2-chloropyrimidine

5-Bromo-2, 4-dichloropyrimidine is dissolved in NHS/MEOH and stirred at rt, and the solvent is removed under reduced pressure. The resulting solid is washed with H20 and dried in vacuo to give the white solid of 5-bromo-2-chloro-pyrimidin-4-ylamine in quantitative yield. The white solid is dissolved in DMSO/H20. To the solution are added DABCO and NaCN, then the resulting mixture is heated to 60 C. The reaction mixture is diluted with water, and extracted with AcOEt. The combined organic extracts are dried over NA2SO4. Flush chromatography on silica gel using AcOEt-Hexane gives 4-amino-5-bromo-pyrimidine-2- carbonitrile as white solid. To a solution of the above product in DMF are added 1-chloro-4- prop-2-ynyl-benzene, (PPh3)2PdCl2 and Cul under N2. The resulting solution is stirred at 80 C, and then sat NH4CI aq is added into the mixture. After stirred for an additional 1 H, THE mixture is extracted with AcOEt twice. The combined organic extracts are washed with NAHCO3 AQ, and dried over NA2SO4. Flash chromatography on silica gel using AcOEt- Hexane gives the title compound.A 100 mL round bottom flask was charged with 5-bromo-2, 4- dichloropyrimidine (10.0 g, 44 mmol), concentrated ammonium hydroxide (100 mL) and THF (150 mL). The resulting mixture was magnetically stirred at room temperature for 12 h. Work-up: the reaction mixture was diluted with water (100 mL) and then extracted with EtOAc (50 mL x 3). The combined organic layers were dried over anhydrous Nantermedate Iyi2coro56dilidrogm .d [4J, jjflpje7carbox(jata(amo-2-chloro-rimidin-4-amineTo a solution of 5-bromo-2, 4dichloro-pyrimidine (150 g; 658 mmol) in THE (445 mL) was added ammoniumhydroxide (25percent in water, 250 mL) and the resufting reaction mixture was stirred at room temperature for 90 mm. The mixture was subsequently evaporated to a small volume and partitioned between ethyl acetate and water. The organic phase wasseparated and washed with water and brine, dried over sodium sulfate, filtered andconcentrated to give 137.3 g (quant. yield) of 5-bromo2-chloro-pyrimidin4-amine.To a solution of S-bromo-2, 4-dichloro-pyrimidine (150 g; 658 mmol) in THF (445 mL) was added ammonium hydroxide (25percent in water, 250 mL) and the resulting reaction mixture was stirred at room temperature for 90 mm. The mixture was subsequently concentrated in vacuo to a small volume and partitioned between ethyl acetate and water. The organic phase was separated and washed with water and brine, dried over sodiumsulfate, filtered and concentrated to give 137.3 g (quant. yield) of 5-bromo-2-chloro- pyrimidin-4-amine.Synthesis of 5-Bromo-2-chloropyrimidin-4-ylamine (1) :; A solution of 5- bromo-2, 4-dichloropyrimidine (25g, 110 mmol) in 200 mL THF is treated with 47 mL of ammonia (330 mmol, 7. 0M solution in methanol). After stirring for 15 hours the solution is concentrated under reduced pressure and purified by short-filtration (Si02, Hexanes: Ethyl acetate/1 : 1) to yield 21g (92 percent) of 1 as a white solid.A solution of 5- bromo-2, 4-dichloropyrimidine (25g, 110 mmol) in 200 mL THF is treated with 47 mL of ammonia (330 mmol, 7.0M solution in methanol). After stirring for 15 hours the solution is concentrated under reduced pressure and purified by short-filtration (Si02, Hexanes : Ethyl acetate / 1: 1) to yield 21 g (92 percent) of 1 as a white solid.A stirred solution of 5-bromo-2, 4-dichloropyrimidine (5.0 g, 0.0220 mol, 1.0 eq, Combi blocks) in THF, at 0°C, was purged with N gas for 1 h while monitoring by TLC. After completion of the starting material, the mixture was quenched with water and extracted with EtOAc. The organic layer was dried over NaA solution of 5-bromo-2, 4-dichloropyrimidine (8.54 g, 37.48 mmol) in methanol (12 mL) was added dropwise over 10 minutes to an ice-bath cooled solution of 7M ammonium hydroxide (60 mL, 420 mmol) in methanol (60 mL) and the resulting solution was stirred at room temperature for 24 hours.

Molecular Weight:208.44
XLogP3:1.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:206.91989
Monoisotopic Mass:206.91989
Topological Polar Surface Area:51.8
Heavy Atom Count:9
Complexity:102
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes