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.
A mixture of ethyl 4,6-dimethyl-2-(4-methylpyridin-3-yl)pyrimidine-5-carboxylate (23)(23 mg, 85 mmol) and lithium hydroxide (50 mg, 2.09 mmol) in ethanol (3 mL) was heated at reflux for 3 h. The solvent was removed in vacuo before the residue was purified via reverse phase(C18) HPLC with a gradient elution of H2O/MeOH (100/0% to 10/90%) to afford compound 27 as an orange-brown solid (18 mg, 87%). 1HNMR (D2O, MeOD) d: 8.77 (s, 1H), 8.43 (d, J4.8 Hz, 1H), 7.39 (d,J4.8 Hz, 1H), 2.59 (s, 6H), 2.53 (s, 3H). 13C NMR (D2O, MeOD) d:170.5, 163.2, 162.6, 150.8, 149.8, 149.0, 136.3, 133.8, 127.5, 22.3, 20.4.LRMS (ESI): m/z 244.1 [MH] (100%); (ESI): m/z 242.0 [MH](100%).A solution of 4,6-dimethyl-2-(4-methylpyridin-3-yl)pyrimidine-5-carboxylic acid (27) (40 mg, 0.16 mmol), ()-tert-butyl 2-methylpiperazine-1-carboxylate45 (36 mg, 0.18 mmol), HOBt(24 mg, 0.18 mmol), EDCI (36 mg, 0.18 mmol) and DIPEA (0.08 mL,0.33 mmol) in DCM (10 mL) was stirred at room temperature for 18 h. The reaction mixture was diluted in H2O, extracted with DCM (310 mL), and the combined organic layers concentrated to 3 mL.To the solution was then added 10 drops of TFA before stirring for 3 h. The reaction mixture was then extracted with H2O (33 mL)and the combined aqueous layers freeze dried. The residue was purified via reverse phase (C18) HPLC with a gradient elution ofH2O/MeOH (100/0% to 10/90%), to afford the desired product asa pale yellow solid (4 mg, 7%) as a mixture of conformers. 1H NMR (MeOD) d: 8.44 (br s, 1H), 7.64e7.58 (m, 1H), 7.45 (m, 1H), 7.15e7.07(m, 1H), 4.59 (m, 2H), 3.95 (br s, 2H), 3.63e3.06 (complex, 6H), 2.39(br s, 3H), 1.32 (m, 3H). 13C NMR (MeOD) d: 157.0, 148.9, 147.8,139.2, 129.7, 129.4, 127.4, 127.0, 125.2, 123.4, 123.1, 113.6, 113.3, 52.0,51.9, 47.1, 30.7, 19.9, 17.1, 16.9. HRMS (APCI): m/z calcd forC18H24N5O [MH]: 326.1981, found: 326.1978; (APCI): m/z calcdfor C19H22N4O [MH]: 324.1824, found: 324.1829., 120737-78-2
The synthetic route of 120737-78-2 has been constantly updated, and we look forward to future research findings.
Reference：
Article; Lim, Zelong; Duggan, Peter J.; Wan, Soo San; Lessene, Guillaume; Meyer, Adam G.; Tuck, Kellie L.; Tetrahedron; vol. 72; 9; (2016); p. 1151 – 1160;,
Piperazine – Wikipedia
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