Preparation of Phthalazine Amides

Most of the routes to such amides have been covered already by primary synthesis (Chapter 8), by aminolysis of phthalazinecarboxylic acids (Section 14.1.2), by aminolysis of phthalazinecarbonyl halides (Section 14.2), by aminolysis of phthalazinecarboxylic esters (Section 14.3.2), and by passenger introduction (most chapters). One major and several minor preparative methods are illustrated in the following examples. 

Note These processes may be used to afford amides or thioamides but not the corresponding hydrazides. The hydrolysis of phthalazinecarbonitriles can give phthalazinecarboxylic acids unless conditions are controlled carefully or the Radziszewski procedure (H2O2, HO ) is adopted. 

1-Phthalazinecarbonitrile (63, R = H) gave 1-phthalazinecarboxamide (64, R = H) (K2CO3, H2O2, AcMe, 20°C, 12 h 24%) 4-methyl-1-phthalazi-necarbonitrile (63, R = Me) gave 4-methyl-1-phthalazinecarboxamide (64, 

4-(3-Chloro-4-methoxybenzylamino)-l-(4-hydroxypiperidino)-6-phthalazme-carbonitrile (65, R = CN) gave the corresponding 6-phthalazinecarboxamide 

2-(2-Cyanoethyl)-4-phenyl-l(277)-phthalazinone (66) gave 4-phenyl-2-(2-thio-carbamoylethyl)-l(2//)-phthalazinone (67) (substrate, pyridine, Et2N, 5°C, 2h H2S, 0°C, 15 min sealed, 20°C, 2 days 89%) homologs likewise.  

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