反应详情

温度

60 °C

5-bromo-2-[2-(4-isopropylsulfonylphenyl)-5-trityl-pyrrolo[2,3-b]pyrazin-7-yl]isoindolin-1-one (100 mg, 0.1327 mmol), 1H-pyrazol-5-ylboronic acid (17.81 mg, 0.1592 mmol) and Na2CO3 (200 μL of 2 M aqueous solution, 0.40 mmol) combined in 1,4-dioxane (1.5 mL). Mixture de-gassed (×3 vacuum-N2 cycles). Pd(tBu3P)2 (6.782 mg, 0.01327 mmol) added and mixture de-gassed (×3 cycles) then heated overnight at 60° C. Reaction mixture partitioned between DCM and water. Aqueous phase extracted with DCM. Combined organics dried and concentrated. Residue taken up in DCM (2 mL) and Et3SiH (106.0 μL, 0.6635 mmol) then TFA (0.3 mL) added under N2. Mixture stirred for 48 h then concentrated and residue azeotroped with DCM (×3). Residue purified by hplc to give the title compound (14 mg, 21%); 1H NMR (400 MHz, DMSO) 1.22 (6H, d), 3.50 (1H, sep), 5.58 (2H, s), 6.90 (1H, d), 7.83-7.87 (2H, m), 8.00 (2H, d), 8.05 (1H, d), 8.25 (1H, s), 8.53-8.57 (3H, m), 9.11 (1H, s), 12.33 (1H, vbrs), 13.10 (1H, s); MS (ES+) 499.0.

1. customMixture de-gassed (×3 vacuum-N2 cycles)
2. custommixture de-gassed (×3 cycles)
3. customReaction mixture
4. custompartitioned between DCM and water
5. extractionAqueous phase extracted with DCM
6. customCombined organics dried
7. concentrationconcentrated
8. concentrationthen concentrated
9. customresidue azeotroped with DCM (×3)
10. customResidue purified by hplc