2-Fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)benzoic acid

S3, 10.6 g (40 mmol) of the solid obtained in the step S2 and 80 mL of water were added to the flask, and the mixture was cooled to 8 ° C, and 2.90 mL (60 mmol) of the mass fraction of 80percent hydrazine was added dropwise, and then returned to 25 ° C, and stirring was continued. , react 4h, then join4mL of acetone was stirred for 30min, then added with 13mL of 4mol / L NaOH aqueous solution heated to 90 ° C for 1h, cooled to room temperature, the aqueous phase was extracted with 45mL of methyl tert-butyl ether, and then adjusted to a pH of about 4 with hydrochloric acid, a white solid precipitated , filtered, 40mL cold water floatWashed and recrystallized from ethyl acetate to give 9.7 g of a white solid, yield: 91percent.(3) A solution of sodium hydroxide (0.105 mol) in ethanol (50 mL) and hydrazine hydrate (17 mL) were stirred at a temperature of 70 ° C to obtain a homogeneous mixed solution pumped from the pump E 10 to the third mixing valve 11, pump E11. The flow rate was 2.2 mL/min; and the reaction effluent obtained in the step (2) was 2-fluoro-5-(3-oxo-3H-isobenzofuran-1-ylmethylene)benzonitrile.(0.022 mol) flowed into the third mixing valve at a flow rate of 1.56 mL/min. After thorough mixing, the pump was pumped into a third microreactor in the third continuous microchannel reaction unit for reaction at a reaction temperature of 70 ° C and a residence time of 10 min, the first receiving device 13The reaction effluent was collected, the reaction effluent was cooled to room temperature, and 2 mol/L of dilute hydrochloric acid was added to adjust the pH to 4, stirred for 20 min, and then poured into water (50 mL) and ethyl acetate (50 mL), and the mixture was separated, filtered, washed. And dry to get the anti-tumor drug olapa2-fluoro-5-[(4-oxo-3, 4-dihydronaphthyridin-1-yl)methyl]benzoic acid(Compound 3), the yield was 91percent.13N sodium hydroxide solution (50 mL) was added to an aqueous solution (200 mL) containing compound f (37 g, 0.14 mol), and the mixture was heated to 90 ° C for 1 hour. After the reaction was reduced to 70 ° C, hydrazije hydrate (100 mL, 2 mol) was added and the temperature was stirred for 18 hours. The reaction solution was cooled to room temperature and the above system was adjusted to pH = 4 with 8N hydrochloric acid. The filter was washed twice with water (60 mL), twice with diethyl ether (50 mL) and dried in vacuo to give a white solid g: 5 - ((4-oxo-3, 4-dihydrazizin-1-yl) methyl) benzoic acid (30.1 g, yield 77percent).The above semi dried compound 2-fluoro-5-[(3-oxo-2-benzofuran-1 {3H)- ylidene)methyl] benzonitrile (IV) as obtained by example-1 was suspended in water (500 imL) at room temperature followed by addition of aqueous solution of NaOH (50 g). The resulting reaction mixture was stirred at 60°C to 70 °C. After completion of the hydrolysis, it was cooled to room temperature and acidified by addition of cone. HCI until the pH was changed to 5-6. Then hydrazine hydrate (1 67 g) was added. The resulting reaction mass was stirred at 60°C to 70 °C. The reaction mass was cooled to room temperature, acidified by addition of cone. HCI until the pH was changed 4.0-4.5. The stirring was continued further at room temperature. The obtained precipitate was filtered and washed with water. The crude compound was purified by using isopropanol (or any other polar solvent) to afford pure 2- fluoro-5-[(4-oxo-3, 4-di hydrophthalazin-1 -yl)methyl]benzoic acid (V) as a solid (70 g). (Yield: 68percent)b.

Molecular Weight:298.27
XLogP3:2.2
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:3
Exact Mass:298.07537038
Monoisotopic Mass:298.07537038
Topological Polar Surface Area:78.8
Heavy Atom Count:22
Complexity:494
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes