Synthesis and Biological Evaluation of Phthalazinone Inhibitors of ...

(3) Ethyl 2-(3-methyl-4-oxo-3,4-dihydrophthalazin-1-yl)acetate. 1 H NMR
(DMSO-d6, 400 MHz): (8.21, d, 1H, J= 8 Hz), (7.96, t, 1H, J= 8 Hz), (7.90, 2H), (4.14, t,
2H, J= 8 Hz), (4.10, s, 3H), (1.19, t, 3H, J= 10 Hz).
(4) Ethyl 2-(4-oxo-3,4-dihydrophthalazin-1-yl)acetate. 1 H NMR (DMSO-d6, 400
MHz): (8.12, d, 1H, J= 8 Hz), (7.80, t, 1H, J= 7 Hz), (7.71, 2H), (3.96, q, 2H, J= 6-8 Hz),
(3.90, s, 2H), (3.19, s, 1H), (1.02, t, 3H, J= 8 Hz).
General procedure for the synthesis of 4-oxopthalazinyl-1-acetic acids.
A solution of ester 3 or 4 (9.0 g, 37 mmol) and 10 eq. 3M NaOH (122 mL) in
THF was refluxed for 3 hr under nitrogen atmosphere. The reaction mixture was
acidified with 1.2 eq of 10 M HCl (47 mL), diluted with water, and extracted with
CHCl3, which was dried with anhydrous MgSO4. Evaporation of CHCl3 yielded 7.9 g
(5) or 7.8 g (6) (99%) of the desired product.
(5) 2-(3-methyl-4-oxo-3,4-dihydrophthalazin-1-yl)acetic acid. 1 H NMR (DMSOd6,
400 MHz): (9.20, d, 1H, J= 8 Hz), (7.94, t, 1H, J= 8 Hz), (7.88, 2H), (3.99, s, 2H),
(3.71, s, 3H).
(6) 2-(4-oxo-3,4-dihydrophthalazin-1-yl)acetic acid. 1 H NMR (DMSO-d6, 400
MHz): (8.14, d, 1H, J= 8 Hz), (7.83, t, 1H, J= 8 Hz), (7.74, m, 2H, J= 8 Hz), (3.94, s, 2H),
(2.39, s, 1H).
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