反应详情

温度

87.5 °C

A flask was charged with 7-iodo-1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine (0.200 g, 0.442 mmol, Example #41, Step C), 5-methoxy-1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (0.140 g, 0.486 mmol, Preparation #31), Pd(PPh3)4 (0.036 g, 0.031 mmol, Strem) and Na2CO3 (0.117 g, 1.11 mmol) in 1,4-dioxane:water (3:1, 10 mL). The reaction mixture was heated at about 85-90° C. for about 5 h. The reaction mixture was filtered, concentrated to dryness under reduced pressure to give a crude solid that was added to a microwave reaction vessel. MeOH (3 mL) and aqueous NaOH (5 N, 0.412 mL, 2.06 mmol) were added and the vessel was sealed and heated to about 120° C. in a microwave for about 20 min (250 psi maximum pressure, 2 min ramp time, 300 max watts). The reaction mixture was filtered and washed with MeOH. The filtrate was concentrated in vacuo, and purified by silica gel chromatography eluting with a gradient of 5-68% EtOAc in heptane to give 7-(5-methoxy-1-methyl-1H-indol-3-yl)-1-methyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine (0.015 g, 22% over 2 steps): LC/MS (Table 2, Method d) Rt=1.30 min; MS m/z: 332 (M+H)+.

1. filtrationThe reaction mixture was filtered
2. concentrationconcentrated to dryness under reduced pressure
3. customto give a crude solid that
4. additionwas added to a microwave reaction vessel
5. customthe vessel was sealed
6. temperatureheated to about 120° C. in a microwave for about 20 min (250 psi maximum pressure, 2 min ramp time, 300 max watts)
7. filtrationThe reaction mixture was filtered
8. washwashed with MeOH
9. concentrationThe filtrate was concentrated in vacuo
10. custompurified by silica gel chromatography
11. washeluting with a gradient of 5-68% EtOAc in heptane