反应详情

HATU (1.1 g) and DIPEA (1.0 mL) were added to a DMF (5.0 mL) solution of 4-[(E)-4-(4-formylphenyl)but-3-en-1-yn-1-yl)benzoic acid (0.54 g) as obtained in Example 23-(2), and the mixture was stirred for 2 hours and 20 minutes at room temperature. HATU (1.1 g) was further added, and the mixture was stirred for 40 minutes at room temperature. N,N2,O-trimethyl-3-oxoserinamide hydrochloride (Intermediate 5-2, 0.57 g) was added, and the mixture was stirred for 20 minutes at 80° C. The reaction mixture was cooled to room temperature, and ethyl acetate and water were added to isolate the organic layer. The extract was washed sequentially with water and brine, and dried over anhydrous magnesium sulfate. The desiccant was filtered out, and then the solvent was distilled off under reduced pressure. Chloroform, IPE and ethyl acetate were added to the resulting residue, the insolubles were filtered out, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by OH type silica gel column chromatography (gradient elution with chloroform/methanol=100/0→10/1) to obtain 1-formyl-4-[(1E)-4-(4-{[1-methoxy-3-(methylamino)-1,3-dioxopropan-2-yl](methyl)carbamoyl}phenyl)but-1-en-3-yn-1-yl]benzene (orange oil) (0.61 g, 74%).

1. customas obtained in Example 23-(2)
2. stirringthe mixture was stirred for 40 minutes at room temperature
3. stirringthe mixture was stirred for 20 minutes at 80° C
4. temperatureThe reaction mixture was cooled to room temperature
5. customto isolate the organic layer
6. washThe extract was washed sequentially with water and brine
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationThe desiccant was filtered out
9. distillationthe solvent was distilled off under reduced pressure
10. additionChloroform, IPE and ethyl acetate were added to the resulting residue
11. filtrationthe insolubles were filtered out
12. concentrationthe filtrate was concentrated under reduced pressure
13. customThe resulting residue was purified by OH type silica gel column chromatography (gradient elution with chloroform/methanol=100/0→10/1)