With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.259808-67-8,1-Boc-3,3-Dimethylpiperazine,as a common compound, the synthetic route is as follows.
259808-67-8, General procedure: The appropriate carboxylic acid (1.0 equiv) is dissolved in DMF or NMP (0.03 to 0.4M) before HATU (1.1 to 1.5 equiv), or T3P (1 to 5 equiv) the corresponding amine (1.0 to 1.5 equiv) and Hunig?s base (3.0 to 5.0 equiv) are added (the addition order of the reagents may vary) The mixture is stirred at room temperature for 45 mm. to 72h. Any one of these 3 work-up procedures can be employed:1. Water or aq. ammonium chloride is added and the aq. phase is extracted with EtOAc. The combined organic phase is washed with brine, dried over MgSO4, filtered and the filtrate evaporated under reduced pressure affording the title compound which is used in the subsequent step without further purification.2. Water or aq. ammonium chloride is added and the aq. phase is extracted with EtOAc. The combined organic phase is washed with iN HCI, sat. aq. NaHCO3 and brine, dried over Na2SO4, filtered and the filtrate evaporated under reduced pressure affording the title compound which is used in the subsequent step without further purification.3. The volatiles are removed under reduced pressure and the residue is purified by flash chromatography on silica gel or by mass-directed reverse phase HPLC, affording the title compound; The intermediate is prepared according to General Procedure 1 using a solution of Intermediate A (10.0 g, 28.3 mmol) in DMF (110 mL), HATU (12.0 g, 31.6 mmol), tert-butyl 3,3- dimethylpiperazine-1-carboxylate (6.64, 31.0 mmol) and DIPEA (12.5 ml, 71.8 mmol) affording the title compound (15.38 g, quantitative yield) as a pale yellow solid, which is used directly in the next step. 1H NMR (400 MHz, DMSO-d6) 6 8.16 (dd, J = 11.0, 2.0 Hz, 1H), 8.07 – 7.97 (m, 1H), 7.82 (s, 1H), 7.76 – 7.64 (m, 1H), 7.51 (s, 1H), 3.85 (s, 2H), 3.57 – 3.38 (m, 4H), 1.52 (s, 1OH), 1.48 (s, 6H), 1.42 (s, 9H). ESI-MS m/z calc. 543.2300, found 546.10 (M+1) Retention time: 1.23 minutes using method J.
As the paragraph descriping shows that 259808-67-8 is playing an increasingly important role.
Reference£º
Patent; VERTEX PHARMACEUTICALS INCORPORATED; LIU, Bingcan; DORICH, Stephane; DE LESELEUC, Mylene; DUPONT-GAUDET, Kristina; JAMES, Clint, Alwyn; VAILLANCOURT, Louis; BEAULIEU, Marc-Andre; STURINO, Claudio; (236 pag.)WO2018/57588; (2018); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics