541-16-2, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 541-16-2 as follows.
2) Preparation of 2-cyclopropylmethyl-4-[2,2-di(tert-butoxycarbonyl)ethyl]-6-(3-fluoro-4-methoxyphenyl)-2H-pyridazin-3-one After 55% sodium hydride (322 mg, 7.38 mmol) was added to a solution of di-tert-butyl malonate (970 mg, 4.48 mmol) in N,N-dimethylformamide (10 mL), 4-bromomethyl-2-cyclopropylmethyl-6-(3-fluoro-4-methoxyphen yl)-2H-pyridazin-3-one (1.8 g, 4.90 mmol) was added under ice-cold stirring. The reaction mixture was stirred at room temperature for 1 hour, poured into water, and extracted with ethyl acetate. The extract was washed with brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue was isolated and purified by chromatography on silica gel (hexane/ethyl acetate=3/1) to yield the title compound as a yellow powder (yield: 1.39 mg, 61.8%). 1H NMR (400 MHz, CDCl3) delta: 0.44-0.50 (2H, m), 0.50-0.58 (2H, m), 1.41 (18H, s), 1.56 (1H, m), 3.12 (2H, d, J=7.8 Hz), 3.87 (1H, t, J=7.8 Hz), 3.94 (3H, s), 4.09 (2H, d, J=7.8 Hz), 7.01 (1H, dd, J=8.5, 8.5 Hz), 7.43 (1H, d, J=8.5 Hz), 7.50 (1H, s), 7.57 (1H, dd, J=12.4, 2.2 Hz).
According to the analysis of related databases, Di-tert-Butyl malonate, the application of this compound in the production field has become more and more popular.
Reference:
Patent; KOWA CO., LTD.; US2004/2497; (2004); A1;,
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