With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.120737-78-2,tert-Butyl 2-methylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.
To a solution of tert-butyl 14-((6-(tert-butylsulfonyl)-4-((4,5-dimethyl-lH-pyrazol-3- yl)amino)quinazolin-7-yl)oxy)-3,6,9,12-tetraoxatetradecan-l-oate (200 mg, 0.300 mmol) in DCM (2 mL) was added hydrochloric acid (2.253 mL, 9.01 mmol) 4M in dioxane and the reaction was stirred at 20 C under an atmosphere of nitrogen for one hour. The volatiles were removed under vacuum, and to the resulting residue was added DCM (2 mL) and DMF (200ul), DIPEA (0.210 mL, 1.202 mmol), tert-butyl 2-methylpiperazine-l-carboxylate (0.085 mL, 0.360 mmol) and l-ethyl-3-(3- dimethylaminopropyl)carbodiimide (69.1 mg, 0.360 mmol). The reaction was stirred at room temperature under an atmosphere of nitrogen for 3 days. The reaction was diluted in 50 mL EtOAc, washed with 50 mL saturated sodium bicarbonate solution, 50 mL water, 50 mL 2 M HCI and 50 mL brine. The aqueous layer was neutralised with saturated sodium bicarbonate solution, and washed with 3 x 100 mL EtOAc. The organic layer was passed through a Biotage phase separator and concentrated under vacuum to afford the title compound (75 mg, 0.095 mmol, 32 % yield). LCMS RT= 0.83 min, ES+ve 792. (2R,5S)-Tert-butyl 5-((4-(14-((6-(tert-butylsulfonyl)-4-((3,4-dimethyl-lH-pyrazol-5- yl)amino)quinazolin-7-yl)oxy)-3,6,9,12-tetraoxatetradecan-l-oyl)-2-methylpiperazin-l-yl)methyl)- 4-(2-(6-(4-fluorobenzyl)-3,3-dimethyl-2,3-dihydro-lH-pyrrolo[3,2-b]pyridin-l-yl)-2-oxoethyl)-2- m thylpiperazine-l-carboxylate, 120737-78-2
As the paragraph descriping shows that 120737-78-2 is playing an increasingly important role.
Reference£º
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; CASILLAS, Linda N.; HARLING, John David; MIAH, Afjal Hussain; SMITH, Ian Edward David; RACKHAM, Mark David; (204 pag.)WO2017/182418; (2017); A1;,
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