Heterocyclic Building Blocks-piperazine

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.31166-44-6,1-Cbz-Piperazine,as a common compound, the synthetic route is as follows.

N-Cbz piperazine (8.24 g, 37.4 mmol), 3-iodobenzyl alcohol 265 (7g, 29.9 mmol), 2-bis(tert-butyl)phosphinobiphenyl (1.8 g, 6.0 mmol), palladium acetate (1.34 g, 6.0 mmol) and cesium carbonate (14.6 g, 44.9 mmol) were combined with benzene (72 mL) at ambient temperature. This mixture was purged with argon and heated to 70° C. for 14 h. The reaction mixture was cooled to ambient and diluted with EtOAc (40 mL); the resulting mixture was stirred vigorously for 10 min Solids were removed by filtration, washed with EtOAc (2.x.20 mL) and the filtrate was concentrated in vacuo. The residue was purified by silica gel chromotography (4:1 Hex/EtOAc) to afford 255 (2.29 g, 24percent) as a light-yellow semi-solid., 31166-44-6

31166-44-6 1-Cbz-Piperazine 643495, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; Infinity Pharmaceuticals, Inc.; US2006/25460; (2006); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

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.

Step 1 : tert-butyl 4-(4-fluorophenyl)-3,3-dimethyl-piperazine-l-carboxylate [00400] A32-1 (200.0 mg, 0.933 mmol, 1.00 eq), A32-2 (310.8 mg, 1.40 mmol, 0. 16 mL, (1153) 1.50 eq), f-BuONa (179.4 mg, 1.87 mmol, 2.00 eq) and bis(tri-tertbutylphosphine) Palladium(O) (47.69 mg, 0.093 mmol, 0. 10 eq) were taken up into toluene (6.00 mL). The reaction mixture was stirred at 1 10 C for 2 hour under N2. LCMS and TLC (Petroleum ether: Ethyl acetate=10/l) showed desired compound was found and the starting material was consumed completely. The reaction mixture was concentrated to give a crude product. The residue was purified by Prep- TLC (Petroleum ether: Ethyl acetate= 10/1) to give the A32-3 (260.0 mg, 0.776 mmol, 83. 1 1% yield, 92% purity) as a yellow oil. LCMS (ESI): RT =0.630 min, mass calcd. for C17H25FN2O2 308.19, m/z found 308.9 [M+H]+, 259808-67-8

The synthetic route of 259808-67-8 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; VIVACE THERAPEUTICS, INC.; LIN, Tracy Tzu-Ling Tang; KONRADI, Andrei W.; VACCA, Joseph; SHEN, Wang; COBURN, Craig; (231 pag.)WO2017/58716; (2017); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.78818-15-2,Benzyl 3-oxopiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

78818-15-2, (2R, 3R, 4R)-2- [ (1R)-1- [3,5-Bis (trifluoromethyl) phenyl] [ETHOXY]-3- (4-] fluorophenyl) tetrahydro-2H-pyran-4-methyl methanesulfonate (WO 00/56727-A1 ; 2.32 g, 4.26 mmol) was added to a solution of [4-BENZYLOXYCARBONYLPIPERAZIN-2-ONE] (1.30 g, 5.54 mmol) and sodium hydride (60% dispersion in mineral oil, 170 mg, 4.26 mmol) in N, [N-DIMETHYLFORMAMIDE] (25 mL) and the mixture was stirred at [50 C] for 16 hours. Further sodium hydride (60% dispersion in mineral oil, 85.2 mg, 2.13 mmol) was added the mixture was stirred at 50 [C] for 1.5 hours. The mixture was cooled and the solvent was evaporated under reduced pressure. Water (50 mL) was added and the mixture was extracted with ethyl acetate [(3] x 100 mL). The combined organic fractions were washed with brine (150 mL), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with hexane/EtOAc (70: 30 increasing to 0: 100) to give the title compound (2.06 g, [71%).] m/z (ES+) 683 [(M+1),] 425 [(M+1-CIOHSF6O).]

As the paragraph descriping shows that 78818-15-2 is playing an increasingly important role.

Reference：
Patent; MERCK SHARP & DOHME LIMITED; WO2004/9573; (2004); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.109-07-9,2-Methylpiperazine,as a common compound, the synthetic route is as follows.

EXAMPLE 41 4-(3-Methyl-1-piperazinyl)-1-(2-methylbenzenesulfonyl)-1H-indole (Scheme 1) The compound was prepared from 4-bromo-1-(2-methyl-benzenesulfonyl)-1H-indole and 3-methylpiperazine according to Method 1 to give 110 mg (38%) of a white solid: 1H-NMR (CD3OD) delta 7.92-6.82 (m, 9H), 3.64-3.39 (m, 5H), 3.12-3.03 (m, 1H), 2.92-2.83 (m, 1H), 2.47 (s, 3H), 1.40 (d, J=7 Hz, 3H); MS (ESI) 370.0 (M+H)+; Purity (HPLC) 94%.

109-07-9, 109-07-9 2-Methylpiperazine 66057, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; Caldirola, Patrizia; Nilsson, Bjorn M.; Johansson, Gary; US2002/165251; (2002); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

75336-86-6, (R)-2-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

75336-86-6, To a solution of (R)-methylpiperazine (400 mg) in dichloromethane (20 mL) at 0 0C was added di-tert-butyl dicarbonate (871 mg). The reaction was stirred at room temperature for 4 h and then quenched with water (20 mL) and extracted into dichloromethane (2 x 40 mL). The combined organics were washed with saturated aqueous brine solution (40 mL), dried (MgSO4) and concentrated to give (R)-3-methyl-piperazine-l- carboxylic acid tert-butyl ester as a white solid (669 mg, 84%).

As the paragraph descriping shows that 75336-86-6 is playing an increasingly important role.

Reference：
Patent; PIRAMED LIMITED; GENENTECH, INC.; BAYLISS, Tracy; CHUCKOWREE, Irina; FOLKES, Adrian; OXENFORD, Sally; WAN, Nan, Chi; CASTANEDO, Georgette; GOLDSMITH, Richard; GUNZNER, Janet; HEFFRON, Tim; MATHIEU, Simon; OLIVERO, Alan; STABEN, Steven; SUTHERLIN, Daniel, P.; ZHU, Bing-Yan; WO2008/70740; (2008); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.20327-23-5,1-Cyclopropylpiperazine,as a common compound, the synthetic route is as follows.

4-Cyclopropylmethyl-piperazine-1-carboxylic Acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl Ester The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-cyclopropylpiperazine, yield 62%. Recrystallisation from 0.2 M HCl gave white crystals, m.p. 238-239 C.; 1H NMR (DMSO-d6): delta 11.51 (br s, 1H), 8.61-8.55 (m, 1H), 8.30-8.20 (m, dd, 1H), 7.32-7.19 (m, d+s, 5H), 4.44-4.00 (br, 2H), 3.80-3.40 (br m, 4H), 3.29-2.93 (br m, 4H), 1.28-1.05 (br m, 1H), 0.75-0.58 (m, 2H), 0.50-0.35 (m, 2H).IR (KBr): nu 1730, 1713 (C=O) cm-1.

20327-23-5, The synthetic route of 20327-23-5 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Ebdrup, Soren; de Jong, Johannes Cornelis; Jacobsen, Poul; Hansen, Holger Claus; Vedso, Per; US2003/166644; (2003); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

169447-70-5, (S)-tert-Butyl 2-methylpiperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

6-Chloropyridine-2-carbonitrile (250 mg, 1.8 mmol) and tert-butyl (2S)-2- methylpiperazine-1-carboxylate (433 mg, 2.17 mmol) were added to a reaction tube with DIPEA (377 pi, 2.17 mmol) in DMF (2.5 ml). The tube was then sealed and the reaction stirred at 80 C for 20 hours. The reaction mixture was concentrated in vacuo and the residue was partitioned between EtOAc (25 ml) and sat aq NaHCO3 (25 ml). The organics were separated and the aqueous phase extracted with EtOAc (2 x 20 ml). The combined organics were washed with water (20 ml), brine (20 ml), dried over MgSO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified via flash column chromatography (gradient of 0 – 100% EtOAc in heptane followed by 0-100% MeOH in EtOAc). The product-containing fractions were combined and concentrated in vacuo to give the title compound as a yellow oil (321 mg, 51 %).1HNMR(500 MHz, Chloroform-d) 7.51 (dd, J = 8.8, 7.2 Hz, 1H), 6.96 (d, J = 7.1 Hz, 1H), 6.76 (d, J = 8.8 Hz, 1H), 4.32 (s, 1H), 4.11 (s, 1H), 4.03 -3.88 (m, 2H), 3.36-3.19 (m, 2H), 3.11 – 2.98 (m, 1H), 1.48 (s,9H), 1.17 (d, J = 6.7 Hz, 3H).LCMS Method 2 – Tr = 1.23 mm (ES+) (M+H)+ 288.0, 169447-70-5

The synthetic route of 169447-70-5 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; NAVITOR PHARMACEUTICALS, INC.; O’NEILL, David John; SAIAH, Eddine; KANG, Seong Woo Anthony; BREARLEY, Andrew; BENTLEY, Jonathan; (565 pag.)WO2018/89433; (2018); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.59702-07-7,1-Methylpiperazin-2-one,as a common compound, the synthetic route is as follows.

59702-07-7, [0808] To a solution of (8-((5-cyano-4-((2-methoxyethyl)amino )pyridin-2-yl)carbamoyl)-2-( dimethoxymethyl)-5,6, 7,8-tetrahydro-1 ,8-naphthyridin-3-yl)methyl methanesulfonate(intermediate 170, 368 mg, 0.657 mmol) in DCM(2.7 ml) at room temperature was added NEt3 (0.319 ml,2.301 mmol) followed by 1-methylpiperazin-2-one (120 mg,1.052 mmol). The reaction mixture was stirred at room temperaturefor 2 hand partitioned between DCM and water. Thewater layer was extracted multiple times with DCM, thecombined organic layers were dried using Na2S04 , filteredand evaporated. The crude product was purified by silica gelcolunm chromatography using a gradient ofMeOH (0-3percent) inDCM to yield the title compound as a white solid. (UPLC-MS3) tR 0.87 min; ESI-MS 553.3 [M+Ht. 1H NMR (600 MHz,CDCI3 ) ll13.75 (s, lH), 8.20 (s, lH), 7.64 (br s, lH), 7.58 (s,lH), 5.56 (s, lH), 5.23 (d, lH), 4.06-4.01 (m, 2H), 3.70 (br s,2H), 3.63 (t, 2H), 3.50-3.42 (m, 8H), 3.40 (s, 3H), 3.31 (br s,2H), 3.14 (br s, 2H), 2.96 (br s, 3H), 2.87-2.80 (m, 2H), 2.71(br s, 2H), 2.03-1.96 (m, 2H).

The synthetic route of 59702-07-7 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Novartis AG; Buschmann, Nicole; Fairhurst, Robin Alec; Furet, Pascal; Knoepfel, Thomas; Leblanc, Catherine; Liao, Lv; Mah, Robert; Nimsgern, Pierre; Ripoche, Sebastien; Xiong, Jing; Han, Bo; Wang, Can; Zhao, Xianglin; US2015/119385; (2015); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

17766-28-8, 1-Cyclohexylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

About 17.3kg of 4-((3-bromo-6-oxo-6H-anthra[l,9-cd]isoxazol-5- yl)amino)benzoic acid was mixed with about 238L of DMSO. About 11L of TEA and 12kg of 1-cyclohexyl piperazine were added to the reaction. Temperature was then raised to about 60- 65C. After 2-3 hours, slowly added about 116L of MTBE and MeOH (10: 1) solution and adjusted the temperature to 40-50C. The solid was centrifuged and washed by 22.5L of MTBE and MeOH (10: 1) solution and followed by about 22L of MeOH. Solid was dried under reduced pressure at about 25-30C for 12-24 hours. About 1.8kg phosphoric acid was dissolved in 90L of N-methyl pyrrolidone (NMP). Previously obtained crude product was dissolved in about 163L of NMP. Under about 40C, two solutions were mixed together for 1-2 hours. Then about 5.5kg of ECOSORB C-941 in about 20L of NMP was added to the previously mixed solution. The mixture was stirred for another 2- 3 hours under nitrogen protection before filtration. About 600L of purified water was slowly added to the solution under about 40C. Solid was centrifuged and washed with about 21L of water and followed by about 56L of MTBE. Solid was dried under reduced pressure at about 25- 30C for 8-12 hours to obtain the 4-((3 -(4-cyclohexylpiperazin- l-yl)-6-oxo-6H-anthra[ 1,9- cd]isoxazol-5-yl)amino)benzoic acid at about 98% purity and about 91% yield.

17766-28-8, As the paragraph descriping shows that 17766-28-8 is playing an increasingly important role.

Reference：
Patent; PURDUE PHARMA L.P.; WU, Jay Jie-Qiang; WANG, Ling; (31 pag.)WO2017/27465; (2017); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics