Toluene → N-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]-2-methylsuccinamic acid

反応式

[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][C:19]=1[F:20])[CH2:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9](=[O:16])[NH:8][N:7]=1.[CH3:21][CH:22]1[CH2:26][C:25](=[O:27])[O:24][C:23]1=[O:28].C1(C)C=CC=CC=1>O>[F:20][C:19]1[CH:18]=[CH:17][C:4]([CH2:5][C:6]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:16])[NH:8][N:7]=2)=[CH:3][C:2]=1[NH:1][C:25](=[O:27])[CH2:26][CH:22]([CH3:21])[C:23]([OH:28])=[O:24]

参加物

実験手順

A stirred mixture of 4-(3-amino-4-fluorobenzyl)-2H-phthalazin-1-one (2.02 g, 7.5 mmol; prepared in a manner similar to that described in Example 23), 3-methyldihydrofuran-2,5-dione (0.856 g, 7.5 mmol) and toluene (100 ml) was heated under reflux for 2.5 hours (for the first 30 minutes of this period, traces of water in the mixture were removed by azeotropic distillation). The resulting solid was collected by filtration from the hot mixture, washed with toluene (20 ml) and dried in vacuo to give N-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]-2-methylsuccinamic acid (1.91 g) as an off-white solid, m.pt. 140–144° C.; 250 MHz 1H-nmr (d6-DMSO) δ (ppm): 0.95 (d, 3H) (CH3), 2.2–2.6 (m, 3H) (—CH2CHMe-), 4.1 (s, 2H) (ArCH2—), 6.9–7.2 (m, 2H) (2×ArH), 7.6–7.9 (m, 4H) (4×ArH), 8.1 (d, 1H) (ArH), 9.55 (s, 1H) (chain CONH), 12.0 (br s, 1H) (CO2H), 12.5 (s, 1H) (ring CONH); m/z (M+H)+ 384, 100% purity.