Heterocyclic Building Blocks-piperazine

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.3022-15-9,Piperazine-2-carboxylic acid dihydrochloride,as a common compound, the synthetic route is as follows.

In the cases in which 4-Boc-1-Fmoc-piperazine-2-acetic acid (the compound of formula (XXIV)) was replaced by 4-Boc-1-Fmoc-piperazine-2-carboxylic acid, the starting material was prepared by dissolving 5.25 g (25.85 mmol) of 2-piperazine carboxylic acid 2HCl in 160 mL of 1:1 dioxane/H2O, and adjusting the pH to 11 with 50% NaOH (aq.). A solution of 7.21 g (29.28 mmol) of BOC-ON in 40 mL of dioxane was slowly added (in portions) while maintaining the pH at 11 with 50% NaOH (aq.) during the addition. The reaction was stirred at room temperature for 5 hours, then cooled to 0 C. and adjusted to pH 9.5 with 50% NaOH (aq.). A solution of 7.34 g (28.37 mmol) of FMOC-CI in 40 mL of dioxane was slowly added (in portions), maintaining a pH of 9.5 during the addition with 50% NaOH (aq.). The mixture was warmed to room temperature, stirred for 20 hours, washed with ethyl ether (3*150 mL), adjusted to pH=2-3 with 6N HCl (aq.), and extracted with toluene (3*150 mL). The combined extracts were dried over Na2SO4, concentrated in vacuo to a volume of 150 mL and chilled at -20 C. overnight. The resulting solids were filtered off, washed with hexane and dried in vacuo to give 5.4 g of the desired 4-Boc-1-Fmoc-piperazine-2-carboxylic acid.

3022-15-9, 3022-15-9 Piperazine-2-carboxylic acid dihydrochloride 2723757, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; Berlex Laboratories, Inc.; Pharmacopeia, Inc.; US6432947; (2002); B1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

76003-29-7, 1-Boc-3-Oxopiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

76003-29-7, To a solution of 50.0 mmol of 5 and 60.0 mmol of 7 in 50.0 mL of 1,4-dioxane was added 0.500 mmol of copper (I) iodide followed by the addition of 100 mmol of K3PO4 and 5 mmol of trans-cyclohexanediamine, then the resulting mixture was stirred at 100 C. for 16 h. The reaction mixture was cooled to rt and diluted with 500 mL of H2O. The resulting aqueous solution was extracted with CHCl3. The organic phase was washed with saturated NaCl, dried over MgSO4 and concentrated in vacuo. The crude product was purified by column chromatography to give 43.4 mmol of 8. 4.2.a tert-Butyl 4-(6-aminopyridin-3-yl)-3-oxopiperazine-1-carboxylate 1H NMR (400 MHz, CDCl3) delta 7.97-8.00 (m, 1H), 7.35-7.40 (m, 1H), 6.50-6.54 (m, 1H), 4.54 (br s, 2H), 4.24 (s, 2H), 3.65-3.69 (m, 2H), 3.75-3.80 (m, 2H), 1.50 (s, 9H); MS m/z: 293 (M+1).

76003-29-7 1-Boc-3-Oxopiperazine 3157178, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; ICAgen, Inc.; Astellas Pharma Inc.; US2005/239800; (2005); 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.59878-57-8,1-(Cyclopropylcarbonyl)piperazine,as a common compound, the synthetic route is as follows.

To the solution of 124 mg (0.357 mmol) of Intermediate II-1 in 4.0 ml of dry DCM, 69.5 mg (0.428 mmol) 1-(cyclopropylcarbonyl)piperazine were added and then stirred at room temperature. After 1 h, 151 mg (0.714 mmol) of sodium triacetoxyborohydride were added and stirring was continued at room temperature for further 1 h. Water was added to the reaction mixture and phases were separated. Aqueous phase was extracted 3x with chloroform. Combined organic phases were dried over anhydrous sodium sulphate. After filtration of the drying agent and evaporation of the solvent under reduced pressure, the residue was purified on a chromatographic plate. CHCl3/MeOH 90/10 system was used for separation. After separation, 170 mg (98%) of the compound 1 were obtained. 1H NMR (300 MHz, CDCl3) delta 8.55 (bs; 1H); 7.61 (dd; J = 7.4; 0.8 Hz; 1H); 7.52 – 7.47 (m; 1H); 7.36 – 7.27 (m; 2H); 7.13 – 7.08 (m; 1H); 6.66 (s; 1H); 6.64 (s; 1H); 4.03 – 3.95 (m; 4H); 3.84 (s; 2H); 3.81 – 3.65 (m; 8H); 2.71 – 2.53 (m; 4H); 1.81 – 1.70 (m; 1H); 1.02 – 0.95 (m; 2H); 0.79 – 0.71 (m; 2H). MS-ESI: (m/z) calculated for C27H31N7O2 [M+H]+: 486.59; determined 486.2.

59878-57-8, The synthetic route of 59878-57-8 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; CELON PHARMA S.A.; DYMEK, Barbara; ZAGOZDA, Marcin; WIECZOREK, Maciej; DUBIEL, Krzysztof; STANCZAK, Aleksandra; ZDZALIK, Daria; GUNERKA, Pawel; SEKULAR, Mariola; DZIACHAN, Maciej; (70 pag.)WO2016/157091; (2016); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

55121-99-8, (4-Aminophenyl)(4-methylpiperazin-1-yl)methanone is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

General procedure: To a solution of 2-chloro-4-ethoxy-7-tosyl-7H-pyrrolo-[2,3-d]pyrimidine (which may be prepared according to 02) (1.0 eq), amines (1.0 eq) and xantphos (0.1 eq) in 1,4-dioxane (2.0 mL) and water (0.2 mL) was added potassium carbonate (2.0 eq) and PdCI2(pddf) (0.1 eq). The reaction mixture was stirred overnight at 90 C. The reaction was quenched with water and extracted with EtOAc (20 mL x 3). The combined organic layer was dried over Na2SO4, filtered and concentrated in vacuum. The crude was purified by columnchromatography on silica gel (DCM: MeOH=25:1)to give the desired products D96-D121., 55121-99-8

The synthetic route of 55121-99-8 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; GLAXOSMITHKLINE (CHINA) R&D COMPANY LIMITED; DING, Xiao; LIU, Qian; LONG, Kai; SANG, Yingxia; STASI, Luigi Piero; WAN, Zehong; XU, Qiongfeng; EDGE, Colin Michael; WO2015/113451; (2015); 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.129799-08-2,1-tert-Butyl 3-methyl piperazine-1,3-dicarboxylate,as a common compound, the synthetic route is as follows.

Step A: 1-tert-Butyl 3-methyl 4-formyl-1,3-piperazinedicarboxylate (0085) To a solution of pentafluorophenol in 520 mL of anhydrous ether placed at 0 C. there are successively added 49 g of 1-ethyl-3-(3?-dimethylaminopropyl)-carbodiimide (286 mmol) in portions and 12 mL of formic acid (312 mmol). The batch is stirred at ambient temperature for 2 hours. There is then added a mixture of 32 g of 1-tert-butyl 3-methyl 1,3-piperazinedicarboxylate (130 mmol) and 18 mL of triethylamine (130 mmol) dissolved in 520 mL of CH2Cl2. The batch is stirred overnight at ambient temperature. The reaction mixture is hydrolysed with 1N aqueous HCl solution and extracted with CH2Cl2. The organic phases are then combined and then washed with saturated aqueous NaHCO3 solution and then with saturated aqueous NaCl solution until neutral. After drying over MgSO4, filtering and concentrating to dryness, the product is isolated by chromatography over silica gel (petroleum ether/AcOEt gradient: 0-30%). The title product is obtained in the form of an oil. (0086) IR: nu: C?O: 1674-1745 cm-1 (0087) m/z (C12H20N2O5): 272.1 (M+); 295.121 (M+Na)+; 567.253 (2M+Na)+, 129799-08-2

129799-08-2 1-tert-Butyl 3-methyl piperazine-1,3-dicarboxylate 2756819, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; LES LABORATOIRES SERVIER; VERNALS (R&D) LIMITED; Le Tiran, Arnaud; Le Diguarher, Thierry; STARCK, Jerome-Benoit; Henlin, Jean-Michel; De Nanteuil, Guillaume; GENESTE, Olivier; Davidson, James Edward Paul; Murray, James Brooke; Chen, I-Jen; (36 pag.)US2016/176848; (2016); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

78818-15-2, Benzyl 3-oxopiperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

78818-15-2, A mixture of 1 ,1-dimethylethyl 4-[(4-iodophenyl)oxy]-1-piperidinecarboxylate (D1 ) (10.9 g), 4-benzyloxycarbonylpiperazin-2-one (commercially available for example from Fluorochem) (7.6 g), tripotassium phosphate (6.79 g), Lambda/./V-dimethylethylenediamine (0.29 ml) and copper (I) iodide (257 mg) in dioxane (200 ml) was heated under nitrogen to 100 0C for 24 h. The mixture was allowed to cool to room temperature and partitioned between water and EtOAc. The aqueous solution was extracted with more EtOAc and the combined organic solutions were washed with brine, dried and concentrated. The residue was dissolved in DCM and purified by chromatography on Biotage (400 g) eluting with EtOAc-cyclohexane (2:3 to 1 :1 ) to give the title compound (7.36 g) LCMS RT = 3.45 min.

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

Reference：
Patent; GLAXO GROUP LIMITED; WO2007/9741; (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.103-76-4,N-(2-Hydroxyethyl)piperazine,as a common compound, the synthetic route is as follows.

2-(4-Methylpiperazin-1-yl)ethyl 4-nitrophenyl carbonate To a stirred solution of 1-(2-hydroxyethyl)piperazine (26.0 g, 0.2 mol) in DMF (200 mL) was added formic acid (752 mL, 0.2 mol) and formaldehyde (16.2 g, 0.2 mol, 37percent solution in water) The reaction mixture was cautiously heated at 100° C. for 2 hours then stirred overnight at room temperature. The solvent was removed in vacuo. This procedure was repeated 3 further times to give ~100 g of product. The crude products were combined and distilled under vacuum to give, at 74° C., 2-(4-methylpiperazin-1-yl)ethanol (51 g, 44percent) as a colourless liquid. Analytical LCMS: (System C, RT=0.70 min), ES+: 145.1 [MH]+.

103-76-4, 103-76-4 N-(2-Hydroxyethyl)piperazine 7677, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; Biovitrum AB; US2009/281087; (2009); 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.655225-01-7,tert-Butyl 4-(2-bromoethyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

655225-01-7, Preparation 7.3N-Methyl-N-[2-(piperazin-1 -yl)ethyl]acetamide ditrifluoroacetate. 0.341 g of 60percent NaH in oil is added to a solution of 0.748 g of N- methylacetamide in 80 ml of THF and stirred for 10 minutes at RT. Then 2 g of fe/f-butyl 4-(2-bromoethyl)piperazinecarboxylate is added and stirred for 16 hours at RT. Water is added to the reaction mixture, it is decanted and the organic solvent is evaporated under vacuum. The residue is dissolved in DCM, filtered through a Chem Elut.(R). cartridge, eluting with DCM and the solvents are evaporated under vacuum. The residue is purified by preparative HPLC and a white solid is obtained. The solid is dissolved in 5 ml of DCM, 1 .2 ml of TFA is added and it is stirred for 16 hours at RT. The reaction mixture is diluted by adding 100 ml of toluene and the solvents are concentrated under vacuum.1 .5 g of the expected compound is obtained.

The synthetic route of 655225-01-7 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; SANOFI; BADORC, Alain; BOLDRON, Christophe; DELESQUE, Nathalie; FOSSEY, Valerie; LASSALLE, Gilbert; YVON, Xavier; WO2012/146318; (2012); 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.57184-25-5,1-(Cyclopropylmethyl)piperazine,as a common compound, the synthetic route is as follows.

4-Cyclopropylmethyl-piperazine-1-carboxylic acid 4-(4-trifluoromethyl-phenoxy)-phenyl Ester The hydrochloride of the title compound was prepared from 4-(4-trifluoromethyl-phenoxy)-phenyl chloroformate and 1-cyclopropylmethyl-piperazine, yield 43%. White crystals, m.p. 238-2390C; IR (KBr): nu 1725 (C=O) cm-1.

57184-25-5, As the paragraph descriping shows that 57184-25-5 is playing an increasingly important role.

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

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.

A Pyrex yessel was charged with magnetic stirring bar. (2.0 g. 11.42 mmol) of 2-methoxy-4-(oxiran-2-yl) benzonitrile, (3.70 g, 17.12 mmol) of tert-butyl (3R)-3-(hydroxymethyl)piperazine- 1 -carboxylate, and 6 m of EtOH. Then it was introduced in the microwaye reactor and irradiated at 150 C for 3 h. The mixture was cooled to room temperature and the solyent was eyaporated and the resulting residue was purified by column chromatography (silica gel, 1- 20% dichloromethane/MeOH) which afforded the product as a mixture of twodiastereomers (1:1) LCIMS: (IE, miz) [(M + 1) – t-Bu]± = 336.41

278788-66-2, As the paragraph descriping shows that 278788-66-2 is playing an increasingly important role.

Reference：
Patent; MERCK SHARP & DOHME CORP.; PASTERNAK, Alexander; DE JESUS, Reynalda, Keh; DING, Fa-xiang; DONG, Shuzhi; FRIE, Jessica; GU, Xin; JIANG, Jinlong; SHAHRIPOUR, Aurash; PIO, Barbara; TANG, Haifeng; WALSH, Shawn; WO2014/126944; (2014); A2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics