반응 #1590544

반응 방정식

potassium carbonate

[3-chloro-4-(cyclopropylcarbamoyl)phenyl]boronic acid

6-bromo-3-iodo-8-methanesulfonyl-imidazo[1,2-a]pyrazine

isobutylamine

→

4-{6-bromo-8-[(2-methylpropyl)amino]imidazo[1,2-a]pyrazin-3-yl}-2-chloro-N-cyclo propylbenzamide

수율 62.2%

용매

THF

반응 조건

후처리

1. 1
   workup.STIRRINGAfter stirring for 96 h at 65° C.
2. 2
   농축the mixture was concentrated in vaccuo
3. 3
   세척washed with water
4. 4
   건조After drying over sodium sulphate and filtration
5. 5
   기타the solvent was evaporated
6. 6
   기타Purification by flash chromatography (ethyl acetate/hexane)

실험 절차

To a stirred solution of 6-bromo-3-iodo-8-methanesulfonyl-imidazo[1,2-a]pyrazine (4.02 g, 10 mmol) in THF (50 mL) was added 1.47 g isobutylamine (20 mmol, 2 eq) in one portion at rt. After stirring overnight, 30 mL 1M potassium carbonate solution (30 mmol, 3 eq), 3.72 g [3-chloro-4-(cyclopropylcarbamoyl)phenyl]boronic acid (15 mmol, 1.5 eq) and 0.81 g Pd(dppf)Cl2 (1 mmol, 0.1 eq) were subsequently added at rt. After stirring for 96 h at 65° C., the mixture was concentrated in vaccuo, taken up in ethyl acetate and washed with water. After drying over sodium sulphate and filtration, the solvent was evaporated. Purification by flash chromatography (ethyl acetate/hexane) yielded 1.88 g (62.20%) 4-{6-bromo-8-[(2-methylpropyl)amino]imidazo[1,2-a]pyrazin-3-yl}-2-chloro-N-cyclo propylbenzamide. 1H-NMR (300 MHz, d6-DMSO): δ=8.51 (1H, d), 8.11 (1H, t), 7.77 (1H, s), 7.74 (1H, s), 7.71 (1H, s), 7.64 (1H, d), 7.51 (1H, d), 3.23 (2H, t), 2.80 (1H, m), 1.99 (1H, m), 0.87 (6H, d), 0.67 (2H, m), 0.50 (2H, m) ppm. UPLC-MS: RT=1.33 min; m/z 463.8 [MH+]; required MW=462.8.

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