With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.314741-40-7,(S)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.
60% Sodium hydride (154 mg, 3.85 mmol) was added portionwise to te/t-butyl (S)-3- (hydroxymethyl)piperazine-l-carboxylate (832 mg, 3.85 mmol) in THF (15 ml) cooled to 0C over a period of 5 minutes under nitrogen. The resulting mixture was stirred at 0C for 10 minutes then allowed to warm to room temperature and stirred for 20 minutes. 7-Bromo-8-chloro-5- fluoroquinazolin-4-ol (970 mg, 3.5 mmol) was added and the mixture heated at 65C and stirred for 2 hours then cooled to room temperature. Further 60% sodium hydride (154 mg, 3.85 mmol) was added and then heated at 65C and stirred for a further 2 hours before cooling to room temperature. The reaction mixture was diluted with EtOAc (100 ml), and water (25 ml). The aqueous phase was taken to pH 5 with acetic acid and separated. The aqueous phase was extracted with EtOAc (100 ml) and the organic phases combined, dried and evaporated. The residue was purified by flash silica chromatography, elution gradient 0 to 20% MeOH in DCM. Pure fractions were evaporated to dryness to afford te/t-butyl (S)-3-(((7-bromo-8-chloro-4-hydroxyquinazolin-5-yl)oxy)methyl)piperazine-l- carboxylate (1.35 mg, 82%) as pale yellow foam. 1H NM (500 M Hz, DMSO, 27C) 1.38 (9H, s), 2.53 – 2.68 (2H, m), 2.68 – 2.85 (2H, m), 2.85 – 2.97 (2H, m), 3.72 (1H, d), 3.87 – 3.99 (2H, m), 4.1 – 4.19 (1H, m), 7.38 (1H, s), 8.14 (1H, s). m/z: ES+ [M+H]+ 473., 314741-40-7
The synthetic route of 314741-40-7 has been constantly updated, and we look forward to future research findings.
Reference£º
Patent; ASTRAZENECA AB; KETTLE, Jason, Grant; BAGAL, Sharanjeet, Kaur; BOYD, Scott; EATHERTON, Andrew, John; FILLERY, Shaun, Michael; ROBB, Graeme, Richard; RAUBO, Piotr, Antoni; (144 pag.)WO2018/206539; (2018); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics