Heterocyclic Building Blocks-piperazine

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.

Example 30 Preparation of 5,7-Dimethoxy-2-(6-(4-methyl-3-oxopiperazin-1-yl)pyridin-2-yl)quinazolin-4(3H)-one Preparation of 5,7-Dimethoxy-2-(6-(4-methyl-3-oxopiperazin-1-yl)pyridin-2-yl)quinazolin-4(3H)-one (Example 30): A mixture of 2-(6-bromopyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one (5 Scheme 21, 0.100 g, 0.278 mmol), 1-methylpiperazin-2-one (7, 0.100 g, 0.667 mmol) and anhydrous lithium hydroxide (0.020 g, 0.83 mmol) in 15-crown-5 (0.9 mL) was heated at 100° C. for 18 h. The mixture was cooled to room temperature and purified by reverse phase HPLC eluting with 10percent to 90percent CH3CN in H2O to afford the title compound (0.02 g, 18percent) as an off-white solid: 1H NMR (500 MHz, DMSO-d6) delta 11.33 (s, 1H), 7.78 (t, J=7.5 Hz, 1H), 7.73 (d, J=7.1 Hz, 1H), 7.08 (d, J=8.3 Hz, 1H), 6.78 (d, J=2.2 Hz, 1H), 6.58 (d, J=2.2 Hz, 1H), 4.25 (s, 2H), 3.97 (t, J=5.5 Hz, 2H), 3.91 (s, 3H), 3.87 (s, 3H), 3.47 (t, J=5.3 Hz, 2H), 2.93 (s, 3H); ESI MS m/z 396 [M+H]+., 59702-07-7

As the paragraph descriping shows that 59702-07-7 is playing an increasingly important role.

Reference：
Patent; RVX Therapeutics Inc.; Fairfax, David John; Duffy, Bryan Cordell; Martin, Gregory Scott; Quinn, John Frederick; Liu, Shuang; Wagner, Gregory Steven; Young, Peter Ronald; US2014/142102; (2014); A1;,
Piperazine – Wikipedia
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With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.278788-66-2,(R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

278788-66-2, To Intermediate I 3 (3.99 g, 21.7 mmol) was added tert-butyl (3i?)-3-(hydroxy- methyl)piperazine-l -carboxylate (5.21 g, 24 mmol), and the mixture was suspended in 1,4-dioxane (100 mL). To this was added DIPEA (4.6 mL, 26 mmol) and the mixture was heated at 80C for 1 h. Further DIPEA (9 mL) was added and the mixture was heated at 100C for 48 h. The reaction mixture was cooled to r.t. and concentrated in vacuo, to yield an orange solid which was triturated with water/ether/dichloromethane and filtered. The solid was discarded, and the filtrate was concentrated in vacuo. The resulting orange oil was purified by flash column chromatography on silica [Biotage SNAP 200g, Isolera, gradient elution (80% EtOAc/isohexanes to 100% EtOAc; followed by 100% DCM to 20% MeOH/DCM)], to yield the title compound (4.51 g, 57.1%) as a yellow oil. LCMS (ES+) 364.8 [M+H]+, RT 1.20 minutes (method 3).

278788-66-2 (R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate 24820286, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; UCB PHARMA S.A.; KATHOLIEKE UNIVERSITEIT LEUVEN, K.U.LEUVEN R&D; FORD, Daniel James; FRANKLIN, Richard Jeremy; GHAWALKAR, Anant Ramrao; HORSLEY, Helen Tracey; HUANG, Qiuya; REUBERSON, James Thomas; VANDERHOYDONCK, Bart; WO2014/96423; (2014); A1;,
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Piperazines – an overview | ScienceDirect Topics

304897-49-2, tert-Butyl 4-(4-aminobenzyl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

4-(4-Carboxy-phenyl)-thiazole-2-carboxylic acid, (100 mg, 0.4 mmol) was combined with HATU (304 mg, 0.8 mmol). This mixture was dissolved in 3 mL of DMF and DIEA (1.0 mmol, 0.17 mL) was added to the solution. Reaction mixture was stirred at room temperature for 30 minutes. To this was added 4-(4-amino-benzyl)-piperazine-l- carboxylic acid tert-butyl ester (233.1 mg, 0.8 mmol). Reaction mixture was heated at 6O0C overnight. The crude was purified using reverse phase HPLC to give the desired product.

304897-49-2, 304897-49-2 tert-Butyl 4-(4-aminobenzyl)piperazine-1-carboxylate 12045001, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; GENELABS TECHNOLOGIES, INC.; WO2008/154601; (2008); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5464-12-0,5464-12-0, 1-(2-Hydroxyethyl)-4-methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

200 mg mixture of 4-chloro-5-[3,5-dichloro-2,6-dimethyl-4-[2-(4-methylpiperazin-l-yl) ethoxy]phenyl] -6-(4-fluorophenyl)thieno [2,3 – ]pyrimidine and 4-bromo-5 – [3 ,5 -dichloro- 2,6-dimethyl-4-[2-(4-methylpiperazin-l-yl)ethoxy]phenyl]-6-(4-fluorophenyl)thieno[2,3-(i] pyrimidine (0.33 mmol), 211 mg ethyl (2i?)-2-hydroxy-3-[2-[[2-(2-methoxyphenyl) pyrimidin-4-yl]methoxy]phenyl]propanoate (0.52 mmol) and 202 mg Cs2C03 (0.62 mmol) was dissolved in 5 mL tert-butanol and the mixture was stirred at 70 °C until no further conversion was observed. It was diluted with ethyl acetate and then it was washed with brine. The organic layer was dried over Na2S04, filtered and concentrated under reduced pressure and purified via flash chromatography using EtOAc and methanol as eluents to obtain ethyl (2i?)-2-[5-[3,5-dichloro-2,6-dimethyl-4-[2-(4-methylpiperazin-l-yl)ethoxy] phenyl] -6-(4-fluorophenyl)thieno [2,3 – ]pyrimidin-4-yl]oxy-3 – [2- [ [2-(2-methoxyphenyl) pyrimidin-4-yl]methoxy]phenyl]propanoate. The obtained intermediate was dissolved in 5 mL dioxane-water 1 : 1 (10 mL/mmol) and 145 mg LiOH x H20 (3.45 mmol) was added. The mixture was stirred at r.t. until no further conversion was observed. Then it was diluted with brine, neutralized with 2 M HC1, extracted with DCM, dried over Na2S04, filtered and concentrated under reduced pressure and purified via preparative reversed phase chromatography using 5 mM aqueous NH4HC03 solution and MeCN as eluents to obtain Preparation 13. 1H NMR (400 MHz, DMSO-d6): 8.89 (d, 1H), 8.60 (s, 1H), 7.81 (d, 1H), 7.53 (dd, 1H), 7.45 (td, 1H), 7.29-7.21 (m, 4H), 7.17-7.13 (m, 1H), 7.14 (d, 1H), 7.04 (td, 1H), 7.01 (d, 1H), 6.76 (t, 1H), 6.20 (d, 1H), 5.45 (dd, 1H), 5.26 (d, 1H), 5.20 (d, 1H), 4.06-4.01 (m, 2H), 3.76 (s, 3H), 3.46 (dd, 1H), 2.79-2.74 (m, 2H), 2.67-2.38 (m, 8H), 2.33 (s, 3H), 2.26 (s, 3H), 2.22 (dd, 1H), 1.73 (s, 3H) HRMS (M+2H)2+ = 462.1310

The synthetic route of 5464-12-0 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; LES LABORATOIRES SERVIER; VERNALIS (R&D) LIMITED; SZLAVIK, Zoltan; KOTSCHY, Andras; CHANRION, Maia; DEMARLES, Didier; GENESTE, Olivier; DAVIDSON, James Edward Paul; MURRAY, James Brooke; SIPOS, Szabolcs; PACZAL, Attila; BALINT, Balazs; (74 pag.)WO2016/207225; (2016); A1;,
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Piperazines – an overview | ScienceDirect Topics

694499-26-8, 4-((4-Methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

694499-26-8, A solution of 2 ml trimethylaluminium (2 M in toluene, 4 mMol) is added to a stirred solution of 355 mg (1.3 mMol) 4-(4-methyl-piperazin-1-ylmethyl)-3- trifluoromethyl-phenylamine in 20 ml toluene at 10 0C under an argon atmosphere. After 1 h at r t, a solution of 436 mg (1.3 mMol) 6-(6-acetylamino- pyrimidin-4-ylmethyl)-naphthalene-1-carboxylic acid methyl ester (Step 9.2) in 5 ml THF is added and the reaction mixture is heated at 90 0C for 45 min. After cooling to 5 0C, a solution of sat. aqueous ammonium chloride (50 ml) is added dropwise. The mixture is poured into EtOAc and filtered over hyflo. The separated aq. phase is extracted with EtOAc. The combined organic phases are washed with water and brine, dried (Na2SO4) and concentrated. The crude product is purified by chromatography (SiO2, CH2CI2 / EtOH/ NH3 90:9:1) and is recrystallised from hot EtOAc and hexane to afford the title compound as a colourless solid: m.p.: 202-2040C.

As the paragraph descriping shows that 694499-26-8 is playing an increasingly important role.

Reference：
Patent; NOVARTIS AG; NOVARTIS PHARMA GMBH; WO2007/104538; (2007); 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.30459-17-7,1-(4-Trifluoromethylphenyl)piperazine,as a common compound, the synthetic route is as follows.

General procedure: To a solution of acid chloride 3a-b (1.0 equiv.), triethylamine (3.0 equiv.) in dry THF, was added arylpiperazines (1.2 equiv.) in dry THF dropwise. The mixture was stirred for 1 h at room temperature. The reaction mixture was diluted with EtOAc, washed with water and brine, dried over anhydrous MgSO4, and concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel (EtOAC:hexanes = 1:1-1:5) to yield the desired products (4a-j). Compound 4d: 1H NMR (300 MHz, CDCl3) delta 7.52 (d, J = 8.6 Hz, 2H), 6.95 (d, J = 8.6 Hz, 2H), 3.92 (m, 4H), 3.37 (s, 4H), 3.03 (m, 2H), 2.56 (m, 1H), 2.35 (m, 1H), 2.13 (m, 1H), 1.34 (m, 2H), 0.96 (s, 9H).

30459-17-7, The synthetic route of 30459-17-7 has been constantly updated, and we look forward to future research findings.

Reference：
Article; Song, Jiho; Lee, Kiho; Kim, Doran; Kim, Jongmin; Lee, Seul; Shin, Jun Seob; Kim, Dong-Seok; Min, Kyung Hoon; Bulletin of the Korean Chemical Society; vol. 35; 2; (2014); p. 666 – 668;,
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.78551-60-7,tert-Butyl 4-benzyl-3-oxopiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

The product of part a) (420 mg) was stirred in TFA (10 ml) for 30 min, then 0 concentrated in vacuo to give the sub-title compound as an oil (415 mg). EPO MS: ESI (+ve): 191 (M+H), 78551-60-7

78551-60-7 tert-Butyl 4-benzyl-3-oxopiperazine-1-carboxylate 10891590, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2006/56752; (2006); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5464-12-0, 1-(2-Hydroxyethyl)-4-methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,5464-12-0

General procedure: To a solution of triphenylphosphine (0.37 mmol) in THF (30 mL) was slowly added diisopropyl azodicarboxylate (0.37 mmol) in 15 min at 0 °C and the mixture was stirred for another 15 min. At the same temperature, to the resulting mixture was slowly added a solution of 20 (0.185 mmol) and corresponding alcohol (0.37 mmol) dissolved in 20 mL THF. The ice bar was removed and the reaction mixture was stirred at room temperature for 12 h. The reaction mixture was evaporated in vacuo, and the residue was purified by column chromatography to afford the product.

The synthetic route of 5464-12-0 has been constantly updated, and we look forward to future research findings.

Reference：
Article; Xing, Weiqiang; Ai, Jing; Jin, Shiyu; Shi, Zhangxing; Peng, Xia; Wang, Lang; Ji, Yinchun; Lu, Dong; Liu, Yang; Geng, Meiyu; Hu, Youhong; European Journal of Medicinal Chemistry; vol. 95; (2015); p. 302 – 312;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

350684-49-0, tert-Butyl 4-(4-aminobenzoyl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

A solution of r -butyl 4-(4-aminobenzoyi)piperazine- 1-carboxylate (2d, 1.7 g, 5.7 mmol, 1 equiv ), 3,5-dibromo-l-methylpyrazin-2(lH)-one (2e, 1.8 g, 6.8 mmol, 1.2 equiv.) and N,N-diisopropylethylamine (1.48 mL, 8.5 mmol, 1.5 equiv.) in N,N-dimethylacetamide (5 mL) was stirred in a sealed vial at 105 C for 30 h. The reaction was cooled to room temperature and EtOAc (20 mL) was then added. The solid precipitate was filtered and dried on high vacuum overnight to provide tert-butyi 4-(4-((6-bromo-4-methyl-3-oxo-3,4- dihydropyrazin-2~yl)amino)benzoy)piperazine-I -carboxylate 2f. The product was carried onto the next step without further purification., 350684-49-0

The synthetic route of 350684-49-0 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; DANA-FARBER CANCER INSTITUTE, INC.; GRAY, Nathanael S.; WANG, Jinhua; DOBROVOLSKY, Dennis; (224 pag.)WO2019/148150; (2019); 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.76003-29-7,1-Boc-3-Oxopiperazine,as a common compound, the synthetic route is as follows.

76003-29-7, With reference to the process described in , 2-nitro-5-bromopyridine (1.01 g, 5.0 mmol), tert-butyl 2-oxo-4-piperazinecarboxylate (1.00 g, 5.0 mmol) and cesium carbonate (3.26 g, 10.0 mmol) were suspended in 1,4-dioxane. Nitrogen gas was bubbled into the suspension for 30 minutes. Xantphos (246 mg, 0.43 mmol) and tris(dibenzylideneacetone)dipalladium (229 mg, 0.25 mmol) were added to the suspension and the reaction mixture was stirred under reflux with heating for two hours. The reaction mixture was cooled to room temperature. Water and ethyl acetate were added to the mixture. The solution was filtered through a Celite pad. The organic phase was separated from the filtrate. The aqueous phase was extracted with ethyl acetate. The extracted organic phases were combined and dried over anhydrous sodium sulfate. The solid was filtered out, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound (1.08 g, yield: 67%). 1H-NMR(CDCl3) delta: 8.67 (1H,d,J=2.4 Hz), 8.32 (1H,d,J=8.8 Hz), 8.15 (1H,dd,J=8.8,2.4 Hz), 4.33 (2H,s), 3.93-3.83 (4H,m), 1.51 (9H,s).

The synthetic route of 76003-29-7 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Teijin Pharma Limited; MIZUNO, Tsuyoshi; SHIMADA, Tomohiro; UNOKI, Gen; MARUYAMA, Akinobu; SASAKI, Kosuke; YOKOSAKA, Takuya; TAKAHASHI, Hiroshi; HORIE, Kyohei; SAKAI, Yuri; (181 pag.)EP3546458; (2019); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics