53242-88-9

94801-28-2

53242-88-9

The general procedure for the synthesis of 4-(4-chlorobenzylidene)-1-(2H)-phthalazinone from (E)-3-(4-chlorobenzylidene)isobenzofuran-1(3H)-one was as follows: intermediate 77 (Stage 2) 4-{[4-chlorobenzylidene]methyl}-1(2H)-phthalazinone (3 lb.) was combined with 3-[(4-chlorophenyl)methyl]-2-benzofuran-1(3H)-one (as prepared in Step 1) (10 equiv., corrected for loss on drying) were suspended in ethanol (37 vol.) and heated to about 85 °C under slight reflux. Subsequently, a mixture of a commercially available hydrazine hydrate solution (e.g., 12 eq. from Aldrich) with ethanol (0.63 vol.) was slowly added through a dropping funnel over a period of 1 hour. After the addition was complete, ethanol (0.63 volume) was added again through the dropping funnel. To remove traces of hydrazine hydrate, the reaction suspension was heated at ~85°C for 14 hours at slight reflux. Upon completion of the reaction, it was cooled to about 20 °C and sampled to check the conversion (HPLC showed 99% conversion). Next, acetone (0.35 v/v) was added to the reaction mixture over 30 minutes (note the exothermic reaction). The quenched suspension was stirred for at least 1 hour and then cooled to about 2°C at 30°C. After continued stirring at about 2 °C for 1 h, the product was isolated by filtration through a suction filter and washed with cold ethanol (about 0-5 °C, 3 x 10.9 v/v). The resulting light brown solid was completely dried on a vacuum suction filter protected by nitrogen to give 4-(4-chlorobenzyl)-1-(2H)-phthalazinone in 90-95% yield (corrected by 1H NMR measurements).1H NMR (400 MHz, DMSO-d6) data: δ 4.30 (s, 2H), 7.35 (m, 4H), 7.88 (m, 3H). 8.26 (d, 1H), 12.62 (s, 1H).