反应详情

A solution of (E)-2-[2-(1H-indazol-3-yl)vinyl]benzoic acid (30 mg, 0.11 mmol) obtained in Step 1 of Example 47 in THF (0.50 mL), was sequentially added with 4-methylmorpholine (25 μL, 0.23 mmol), 2-aminothiazole (17 mg, 0.17 mmol), EDC (31 mg, 0.16 mmol) and 1-hydroxybenzotriazole monohydrate (20 mg, 0.15 mmol), followed by stirring at room temperature for 2.0 hours. The reaction mixture was added with water and ethyl acetate to separate the mixture into organic layer and aqueous layer and the organic layer was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol=100/0 to 95/5) and the obtained compound was crystallized from 4.0 mol/L hydrogen chloride-ethyl acetate solution (1.0 mL)/ethyl acetate (1.0 mL). The obtained solid was added with ethyl acetate and saturated aqueous sodium hydrogencarbonate solution to separate the mixture into organic layer and aqueous layer and the organic layer was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol=15/1) to obtain Compound 138 (8.5 mg, 22%).

1. customto separate the mixture into organic layer and aqueous layer
2. concentrationthe organic layer was concentrated under reduced pressure
3. customThe residue was purified by silica gel column chromatography (chloroform/methanol=100/0 to 95/5)
4. customthe obtained compound was crystallized from 4.0 mol/L hydrogen chloride-ethyl acetate solution (1.0 mL)/ethyl acetate (1.0 mL)
5. additionThe obtained solid was added with ethyl acetate and saturated aqueous sodium hydrogencarbonate solution
6. customto separate the mixture into organic layer and aqueous layer
7. concentrationthe organic layer was concentrated under reduced pressure
8. customThe residue was purified by silica gel column chromatography (chloroform/methanol=15/1)