反应详情

2-((4,6-difluoro-1H-indol-3-yl)thio)acetic acid (160 mg, 0.66 mmol) from Step B, 3-amino-5-methyl-isoxazole (130 mg, 1.32 mmol), PyClu (440 mg, 1.32 mmol), and DIEA (289 μL, 1.65 mmol) were added to dichloroethane (5 mL) and microwave irradiated at 110° C. for 30 minutes. The solvent was removed in vacuo and the remaining residue was dissolved in 5 mL (9:1, methanol:water) and oxone (641 mg, 1.0 mmol) was added and this mixture was stirred at ambient temperature overnight. Water (5 mL) was added and the mixture extracted with ethyl acetate (3×3 mL). The organics were combined, dried over magnesium sulfate, and concentrated in vacuo to give an oily residue which was purified on a silica gel column (0-50% ethyl acetate:hexanes over 19 min) to yield the desired product (62.0 mg, 0.174 mmol, 26% yield over 2 steps). LCMS>99% at 220 nm, RT=1.15 min, m/z=356 (M+1).

1. customirradiated at 110° C. for 30 minutes
2. customThe solvent was removed in vacuo
3. additionwas added
4. extractionthe mixture extracted with ethyl acetate (3×3 mL)
5. dry with materialdried over magnesium sulfate
6. concentrationconcentrated in vacuo
7. customto give an oily residue which
8. customwas purified on a silica gel column (0-50% ethyl acetate:hexanes over 19 min)