With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.171504-98-6,Methyl 1,4-Bis(Boc)-2-piperazinecarboxylate,as a common compound, the synthetic route is as follows.
To a stirring solution of compound 2 (1 g, 2.91 mmol) in dry THF (20 mL) were added LiHMDS (1.0 M in THF) (10.2 mL, 10.2 mmol), paraformaldehyde (69 mg, 2.32 mmol) at -78 C under nitrogen atmosphere. The reaction mixture was brought to RT and stirred for 16 h. After consumption of the starting material (by TLC), the reaction was quenched with ice water (20 mL) and extracted with EtOAc (2 x 50 mL). The combined organic layer was washed with brine solution (2 x 10 mL), dried over Na2S04 and concentrated to obtain crude compound which was purified by column chromatography by eluting 30% EtOAc/ hexanes to afford racemic EE (320 mg, 32%) as white solid. The racemic was separated by chiral HPLC purification to give 75mg each of EE-1 and EE-2. EE-1: 1H-NMR: (400 MHz, DMSO-d6): delta 7.98 (s, 1H), 3.78 (d, / = 12.8 Hz, 1H), 3.67-3.60 (m, 1H), 3.51 (d, / = 13.6 Hz, 1H), 3.41-3.30 (m, 4H), 3.07 (br s, 1H), 1.39 (s, 18H). LCMS (ESI): m/z 340.1 [M+-l]; UPLC: 99.74% EE-2: 1H-NMR: (400 MHz, DMSO-ifc): delta 7.99 (s, 1H), 3.78 (d, / = 12.8 Hz, 1H), 3.65-3.61 (m, 1H), 3.51 (d, / = 13.6 Hz, 1H), 3.40-3.30 (m, 4H), 3.07 (br s, 1H), 1.39 (s, 18H). LCMS (ESI): m/z 340.1 [M+-l]; UPLC: 99.04%, 171504-98-6
The synthetic route of 171504-98-6 has been constantly updated, and we look forward to future research findings.
Reference：
Patent; APTINYX INC.; KHAN, M., Amin; (75 pag.)WO2018/26782; (2018); A1;,
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