反应详情

Diisopropylamine (0.20 mL, 1.5 mmol) in THF (1.5 mL) was cooled to about −74° C. A solution of n-BuLi (1.6 M solution in cyclohexane, 1.03 mL, 1.65 mmol) was added drop-wise over about 15 min. After about 20 min, the solution was added to 1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine (0.250 g, 0.766 mmol) in THF (10 mL) at about −74° C. over about 10 min. After about 1 h at about −74° C., a solution of iodine (0.226 g, 0.889 mmol) in THF (5 mL) was added over about 5 min. After about 2 h at about −74° C., water (20 mL) was added and the reaction mixture was extracted with EtOAc (3×20 mL). The organic layers were combined, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with a gradient of 5-40% EtOAc in heptane to give 7-iodo-1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine (0.27 g, 78%): LC/MS (Table 2, Method d) Rt=2.34 min; MS m/z: 453 (M+H)+.

1. waitAfter about 1 h at about −74° C.
2. waitAfter about 2 h at about −74° C.
3. extractionthe reaction mixture was extracted with EtOAc (3×20 mL)
4. dry with materialdried over anhydrous MgSO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by silica gel chromatography
8. washeluting with a gradient of 5-40% EtOAc in heptane