5-Bromo-4-chloropyrimidine

Pale yellow crystal

To a mixture of 5-bromopyrimidin-4-ol (1-111) (40 g, 0.22 mol) in POCI3 (300 mL) was added in a dropwise manner DIPEA (29 g, 0.22 mol) at room temperature. Then the resulting mixture was heated to reflux for 3 hr. TLC (petroleum ether/EtOAc 1 :1) showed the reaction was complete. Excess POCI3 was removed through distillation under reduced pressure. The residue was poured into ice-water (300 mL) slowly with stirring. The mixture was extracted with EtOAc (2 x 300 mL), the combined organic layers were washed with water (300 mL), brine (300 mL), dried over Na2S04 and concentrated under vacuum. The residue was purified by silica gel chromatography (petroleum ether/EtOAc from 20:1 to 10:1) to give 5-bromo-4-chloropyrimidine (1-112) (25 g, 60percent) as a yellow oil.5-bromo-4-chloropyrimidine15 A stirred solution of 5-bromopyrimidin-4-ol (650mg, 3.73mmol) in POCITo a mixture of 5-bromopyrimidin-4-ol (1-111) (40 g, 0.22 mol) in POCI3 (300 mL) was added in a dropwise manner DIPEA (29 g, 0.22 mol) at room temperature. Then the resulting mixture was heated to reflux for 3 hr. TLC (petroleum ether/EtOAc 1 :1) showed the reaction was complete. Excess POCI3 was removed through distillation under reduced pressure. The residue was poured into ice-water (300 mL) slowly with stirring. The mixture was extracted with EtOAc (2 x 300 mL), the combined organic layers were washed with water (300 mL), brine (300 mL), dried over Na2S04 and concentrated under vacuum. The residue was purified by silica gel chromatography (petroleum ether/EtOAc from 20:1 to 10:1) to give 5-bromo-4-chloropyrimidine (1-112) (25 g, 60percent) as a yellow oil.5-bromo-4-chloropyrimidine15 A stirred solution of 5-bromopyrimidin-4-ol (650mg, 3.73mmol) in POCIStep 4: 5-Bromo-4-hydrazinylpyrimidine[0363] A 100-mL round-bottomed flask was charged with a solution of 5- bromo-4-chloropyrimidine (8 g, 25.00 mmol, 1.00 equiv, 60%) in ethanol (50 mL). To this solution was added hydrazine (10 mL, 99%) drop wise with stirring. The resulting solution was stirred overnight at room temperature. The reaction progress was monitored by TLC (MeOH: DCM = 1: 10). The solids were collected by filtration affording 5-bromo-4-hydrazinylpyrimidine as yellow solid (0.83 g, 18%).To a mixture of To a mixture of (S)-4-((2-acetamidoethyl) (4-(5, 6, 7, 8-tetrahydro-1, 8-naphthyridin-2-yl) butyl)amino)-2-aminobutanoic acid (200 mg, 511 mumol) and To a mixture of (S)-2-amino-4-((2-ethoxyethyl) (4-(5, 6, 7, 8-tetrahydro-1, 8-naphthyridin-2-yl) butyl)amino) butanoic acid hydrochloride (150 mg, 361 mumol) in 4:1 THF/H2O (3 mL) was added To a mixture of (S)-2-amino-4-((2-(4-fluorophenoxy)ethyl) (4-(5, 6, 7, 8-tetrahydro-1, 8-naphthyridin-2-yl) butyl)amino) butanoic acid hydrochloride (150 mg, 312 mumol) in 4:1 THF/H2O (3 mL) was added

Molecular Weight:193.43
XLogP3:1.9
Hydrogen Bond Acceptor Count:2
Exact Mass:191.90899
Monoisotopic Mass:191.90899
Topological Polar Surface Area:25.8
Heavy Atom Count:8
Complexity:80.4
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes