反应详情

7-Iodo-3-(4-phenoxyphenyl)isoxazolo[4,5-c]pyridin-4-amine (0.100 g, 0.233 mmol) in 1,2-dimethoxyethane (4 mL) and water (2 mL) was reacted with an 2-[(E)-3,3-diethoxy-1-propenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.09 g, 0.35 mmol), sodium carbonate (0.05 g, 0.47 mmol) and tetrakis triphenylphosphine palladium (0) (0.02 g, 0.014 mmol) at 90° C. for 18 hours. The solvent was removed in vacuo and the residue was dissolved in acetone/water 95:5 (10 mL) then p-toluene sulfonic acid was added. The mixture was stirred at ambient temperature for 18 hours then evaporated and the residue dissolved in 1,2-dichloroethane (4 mL). Diethylamine (100 mg) was added followed by sodium triacetoxyborohydride (100 mg). The mixture was stirred for 18 hours then the concentrated and by preparative RP-HPLC (Rainin C18, 8 mm, 100 Å, 25 cm; 20% acetonitrile-0.1M ammonium acetate isocratic for 5 minutes, then 20-80% acetonitrile-0.1M ammonium acetate over 30 min, 21 ml/min) followed by treatment with Silica-carbonate and lyophilization: 1H NMR (DMSO-d6, 400 MHz) δ 8.08 (s, 1H), 7.7 (d, 2H), 7.46 (t, 2H), 7.16-7.25 (m, 5H), 6.6 (d, 1H), 6.49 (m, 1H), 6.33 (bs, 2H), 3.25 (d, 2H), 2.50 (q, 4H), 1.0 (t, 6H); Rt=2.90 min (Conditions a), MS m/e: 413 (M−H)−.

1. customThe solvent was removed in vacuo
2. dissolutionthe residue was dissolved in acetone/water 95:5 (10 mL)
3. additionp-toluene sulfonic acid was added
4. customthen evaporated
5. dissolutionthe residue dissolved in 1,2-dichloroethane (4 mL)
6. additionDiethylamine (100 mg) was added
7. stirringThe mixture was stirred for 18 hours
8. concentrationthe concentrated and by preparative RP-HPLC (Rainin C18, 8 mm, 100 Å, 25 cm
9. wait20% acetonitrile-0.1M ammonium acetate isocratic for 5 minutes
10. wait20-80% acetonitrile-0.1M ammonium acetate over 30 min