3-BROMO-8-CHLOROIMIDAZO[1,2-A]PYRAZINE

To a solution of 8-chloro-imidazo[l, 2-a]pyrazine (1.53 g, 0.01 mol) in DCM (30 mL) is added N-bromosuccinimide (1.78 g, 0.01 mol) and the reaction is stirred at room temperature for 2h. After this time the solution is washed with saturated aqueous solution of NaTo the solution of compound 9 (6.47 g, 42.13 mmol) indichloromethane (140 ml) N-bromosuccinimide (7.50 g, 42.13 mmol) was added and the mixture was stirred at roomtemperature for 3 h. The reaction mixture was diluted withdichloromethane and stirred with 10percent aqueous sodium carbonatesolution for 1 h before the layers were separated. The organic layerwas washed with water (2), dried over sodium sulphate, filteredand concentrated under reduced pressure. The crude product was triturated with diisopropyl ether and filtered to give the titlecompound (14.40 g)Intermediate Example 2-1 : Preparation of 3-bromo-8-chloro-imidazo[1 , 2- ajpyrazineTo a stirred solution of 8-chloro-imidazo[1 , 2-a]pyrazine (164.2 g g, 1070 mmol) in 950 mL DMF is added NBS (190.3 g, 1070 mmol) in one portion and the mixture is stirred overnight at rt. The mixture is poured on 9500 mL water, filterd and the residue is washed with water (2 x 1000 mL) and dried in vaccuo to yield 152.6 g (61.4 percent) of the title compound. Step 2: 3-Bromo-8-chloroimidazo[l, 2-a]pyrazine[0314] A solution of 8-chloroimidazo[l, 2-a]pyrazine (15g, 97.4 mmol) in DCM (300 mL) was treated with NBS (19. Ig, 108 mmol) at room temperature and stirred at this temperature for overnight. The reaction was monitored by TLC. After this time, the resulting solution was diluted with 200 mL DCM and washed with saturated solution of NaTo a mixture of 8.-chIoroirnidazo[12.-a]pyrazinc (500 mg, 3.3 rnrnol) in AcOH (5 mL) was added Br2 (800 mg, 5.0 mmol) at RT. The resulting mixture was stirred at RT for 2 days, then poured into water (20 mL) and extracted with EtOAc (15 mL x 3). The combined organic layer was washed with aqueous sodium bicarbonate solution and brine, dried over MgSO, filtered and concentrated in vacuo. The residue was purified by chromatography on silica (9.’16percent EtOAc in petroleum ether) to give the title compound (30() mg) as a yellow solid. LRMSm/z (M+H) 232.2, 234.1 found, 231.2, 234.1 required.The 7-halo compound 101(4.92 g, 20.2 mmol) was mixed with BrExample 102; The 7-halo compound 101 (4.92 g, 20.2 mmol) was mixed with Br3-bromo-8-chloroimidazo [1, 2-a] pyrazine (1.33 g, 5.7 mmol), 1- (2-methoxyethyl) -1H-pyrazole-4-amine (0.96 g, 6.8 mmol) was added to 15 mL of n-butanol, The temperature was raised to 120 C and reacted overnight.The solvent was removed by rotary evaporation, diluted with 30 mL of water, and extracted with ethyl acetate (20 mL * 3). The organic phases were combined, It was washed with 20 mL of saturated brine, dried over anhydrous sodium sulfate, and concentrated.Separation through a silica gel column gave 1.45 g of a pale yellow solid with a yield of 76%.Add 3-bromo-8-chloroimidazo [1, 2-a] pyrazine (1.33 g, 5.7 mmol), 1-methyl-1H-pyrazole-4-amine (0.66 g, 6.8 mmol)And triethylamine (1.15 g, 11.4 mmol) were added to 15 mL of n-butanol, and the temperature was raised to 120 C. and reacted overnight.The solvent was removed by rotary evaporation, diluted with 30 mL of water, and extracted with ethyl acetate (20 mL * 3). The organic phases were combined, It was washed with 20 mL of saturated brine, dried over anhydrous sodium sulfate, and concentrated.1.25 g of a pale yellow solid was isolated on a silica gel column with a yield of 75%.

Molecular Weight:232.46
XLogP3:2.7
Hydrogen Bond Acceptor Count:2
Exact Mass:230.91989
Monoisotopic Mass:230.91989
Topological Polar Surface Area:30.2
Heavy Atom Count:11
Complexity:157
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes