反应详情

A stirred mixture of 4-(3-amino-4-fluorobenzyl)-2H-phthalazin-1-one (0.1 g, 0.37 mmol; prepared in a manner similar to that described in Example 23), 3-hex-2-enyldihydrofuran-2,5-dione (0.068 g, 0.37 mmol) and toluene (10 ml) was heated under reflux for 20 hours, then the resulting solid was collected by filtration from the hot mixture, washed with ethyl acetate (3 ml) and dried in vacuo to give 2-{[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenylcarbamoyl]methyl}oct-4-enoic acid (0.061 g) as an off-white solid, m.pt. 179–181° C.; 250 MHz 1H-nmr (d6-DMSO) δ (ppm): 0.7–0.9 (t, 3H) (CH3), 1.1–1.35 (m, 2H) (—CH2CH3), 1.75–2.0 (m, 2H) (—CH2CH2CH3), 2.0–2.3 (m, 2H) (—CH2CH═CH—), 2.3–2.8 (2×m obscured by DMSO signal, 2H+1H) (—CH2CH(CO2H)CH2—), 4.2 (s, 2H) (ArCH2—), 5.15–5.5 (m, 2H) (—CH═CH—) 6.9–7.2 (m, 2H) (2×ArH), 7.65–8.0 (m, 4H) (4×ArH), 8.2 (d, 1H) (ArH), 12.1 (br s, 1H) (CO2H), 12.6 (s, 1H) (CONH); m/z (M+H)+. 452, 93.7% purity.

1. customprepared in a manner similar to
2. temperaturewas heated
3. temperatureunder reflux for 20 hours
4. filtrationthe resulting solid was collected by filtration from the hot mixture
5. washwashed with ethyl acetate (3 ml)
6. customdried in vacuo