Heterocyclic Building Blocks-piperazine

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.74879-18-8,(S)-(+)-2-Methylpiperazine,as a common compound, the synthetic route is as follows.

Example 15 A 2-liter four-neck flask with a thermometer, condenser and stirrer was charged with 200.4 g (= 2.00 moles) of racemic 2-methylpiperazine, 280.0 g of water and 96.0 g of methanol for perfect dissolution. Then, 300.4 g of 50 wt% D-tartaric acid aqueous solution (150.2 g = 1.000 mole of D-tartaric acid) was added at 40 to 45C, and the temperature was further raised up to 72C, being followed by addition of 120.2 g (= 2.00 moles) of acetic acid and aging at the temperature for 2 hours. The solvent composition was water/methanol = 81.8/18.2 (ratio by weight), and the amount of the solvent based on the racemic 2-methylpiperazine was 2.63 times by weight. Then, cooling was carried out down to 25C, taking 12 hours, and precipitated crystals were collected by filtration. The obtained crystals were dried in vacuum, to obtain 214.8 g (= 0.858 mole) of a diastereomer salt. The optical purity of the salt was 93.9%ee, and the yield of the S-isomer in the obtained salt based on the amount of the S-isomer in the supplied (+/-)-2-methylpiperazine was 83.2%. Subsequently, a 1-liter flask was charged with 380 g of water, and the obtained 214.8 g of crystals {pure (S)-2-methylpiperazine content = 83.4 g} were added. Perfect dissolution was achieved at 80 to 85C, and cooling was carried out down to 15C, taking 12 hours. Precipitated crystals were collected by filtration and dried in vacuum to obtain 187.2 g of a salt. Its optical purity was 99.4%ee, and the yield of the S-isomer in the obtained salt based on the amount of (S)-2-methylpiperazine in the supplied crystals was 89.8%. A 500 ml four-neck flask with a thermometer, condenser and stirrer was charged with 150 g of water, and 185.0 g of (S)-2-methylpiperazine D-tartaric acid salt (= 0.739 mole, optical purity of 2-methylpiperazine = 99.4%ee) obtained before and 69.1 g (= 0.863 mole) of 95% pure calcium hydroxide were added. The slurry was heated up to 70 to 80C, and stirred for 3 hours, then being cooled to room temperature. Subsequently, the non-dissolved salt was filtered away, to obtain the mother liquor. The mother liquor was GC-analyzed, and as a result, it was found that 68.7 g (= 0.686 mole) of optically active 2-methylpiperazine existed in the mother liquor (yield 92.8%). Furthermore, as a result of HPLC analysis, the optical purity of (S)-2-methylpiperazine was 99.4%ee. Then, water was distilled away till about 50 wt% was reached, being followed by addition of 1-butanol, and azeotropic dehydration was carried out till the water content of the system became less than 1 wt%. In a 1-liter four-neck flask, 50.0 g of the (S)-2-methylpiperazine (= 0.499 mole, optical purity 99.4%ee) obtained before was placed, and 440 g of 1-butanol was added for dissolution. The solution was cooled down to 0C, and 92.5 g (= 0.534 mole) of benzyl chlorocarbonate was added dropwise with the liquid temperature kept in a range from 0 to 8C. Then, stirring was carried out at 0C for 2 hours, and 300 g of 1-butanol was distilled away under reduced pressure, being followed by addition of 300 g of water. Subsequently 35% hydrochloric acid water was used to adjust the pH to 1.0, and 220 g of toluene was added, being followed by stirring for 30 minutes. The upper layer was then removed, and the same amount of toluene was added again. The same operation was repeated to carry out washing operation. Subsequently 48% sodium hydroxide aqueous solution was used to adjust the pH of the reaction solution to 12.1. In this case, white turbidity occurred due to liberated 1-benzyloxycarbonyl-3-methylpiperazine. To the white turbid solution, 400 g of toluene was added, and stirring water carried out for 30 minutes. The lower layer was then removed, and the upper layer was concentrated under reduced pressure at 60 to 70C in temperature. Subsequently toluene was distilled away to obtain 88.5 g of a concentrate. Eighty five point .zero grams of the obtained 1-benzyoxycarbonyl-3-methylpiperazine was fed to a thin film distiller (heating surface area 0.02 m2) using a liquid feed pump at 0.6 liter/h. The temperature of the heating medium was 150C, and a low-boiling component was cut at a vacuum degree of 360 Pa, to obtain 82.8 g of a liquid remaining in the distiller. The liquid remaining in the distiller was again fed to the same thin film distiller at 0.6 liter/h using a liquid feed pump. The temperature of the heating medium was 220C, and product distillation was carried out at 87 to 116 Pa in vacuum degree, to obtain 76.1 g of a distillate. The obtained compound was analyzed. As a result, the intended 1-benzyloxycarbonyl-3-methylpiperazine accounted for 99.4 liquid chromatography area %. The impurities showed 0.25 liquid chromatography area % for benzyl alcohol, 0.03 liquid chromatography area % for 1-benzyl-4-benzyloxycarbonyl-2-methylpiperazine, 0.02 liquid chromatography area % for 1-benzyl-2-methylpiperazine and no detection for 1,4-dibenzyloxycarbonyl-2-methylpiperazine (and 0.08 area % for sol…, 74879-18-8

As the paragraph descriping shows that 74879-18-8 is playing an increasingly important role.

Reference£º
Patent; Toray Fine Chemicals Co., Ltd.; EP1548010; (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.475272-54-9,(S)-1-Boc-3-Isopropylpiperazine,as a common compound, the synthetic route is as follows.

2-Amino-4,6-dichloropyrimidine-5-carbaldehyde (2.4 g, 13 mmol) and tert-butyl (35)-3-isopropylpiperazine-l -carboxylate (2.9 g, 13 mmol) in 1,4-dioxane (50 mL) were treated with DIPEA (3.3 g, 5 mL, 25 mmol) and heated at 90C for 6 h. The reaction mixture was cooled and concentrated in vacuo, then partitioned between DCM and water. The organic layers were phase separated and concentrated. The resulting golden foam was taken up in THF (100 mL) with triethylamine (2.7 g, 4 mL, 27 mmol) and methylhydrazine (0.64 g, 0.73 mL, 14 mmol), then stirred for 72 h at room temperature. The reaction mixture was concentrated in vacuo and partitioned between DCM and water, then phase separated. The organic layers were further concentrated in vacuo. The residual foam was taken up in DCM (100 mL), then 4N HC1 in 1,4-dioxane (20 mL) was added and the mixture was stirred overnight. The resultant solution was concentrated in vacuo and triturated with diethyl ether to give the title compound (3.8 g, 95%) as a sticky foam that was >95% pure by LCMS. LCMS (ES+) [M+H]+ 276.2, RT 0.72 minutes (method 2).

475272-54-9, 475272-54-9 (S)-1-Boc-3-Isopropylpiperazine 24820348, apiperazines compound, is more and more widely used in various fields.

Reference£º
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;,
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.325145-35-5,(S)-tert-Butyl 2-ethylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

The product from example 69 part d) (1 g), the product from example 13 part b) (1.263 s g) and MgSO4 (xs) were stirred in THF (50 ml) for 16 h. Sodium triacetoxy borohydride (3.96 g) was added and the reaction stirred for 16 h. The reaction was quenched with water and extracted with ethyl acetate. The organic layer was dried (Na2SO4) and concentrated in vacuo. It was purified by chromatography (silica, (20percent EtOAc/isohexane as eluent)), to give the sub-titled compound as a colourless oil (2.03 g). o MS: APCI (+ve): 469 (M+l), 325145-35-5

The synthetic route of 325145-35-5 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2006/56752; (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.57184-23-3,1-(Cyclohexylmethyl)piperazine,as a common compound, the synthetic route is as follows.

4-Cyclohexylmethyl-piperazine-1-carboxylic Acid 4-(3-chloro-5-trifluoromethyl-pyridin-2-yloxy)-phenyl Ester The hydrochloride of the title compound was prepared from 4-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-phenyl chloroformate and 1-cyclohexylmethyl-piperazine, yield 76%. White crystals, m.p. 265-266 C.; IR (KBr): nu 1732 (C=O) cm-1., 57184-23-3

The synthetic route of 57184-23-3 has been constantly updated, and we look forward to future research findings.

Reference£º
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.109-07-9,2-Methylpiperazine,as a common compound, the synthetic route is as follows.

To a stirred solution of 2- methyl piperazine (l0g, lOOmmol, leq) in ethanol (200mL) was added DIPEA (43.5mL, 250mmol, and the reaction mixture stirred for 10 min.. To this Boc anhydride (21.8mL, lOOmmol, leq) was added at 0¡ãC and the resulting reaction mixture was stirred at room temperature overnight. The progress of reaction was monitored by TLC, which indicated formation of nonpolar spot. The reaction mixture was concentrated and dissolved in DCM (200mL) then washed with water (2 x 80mL) followed by brine solution. The combined organic layer was dried over Na2SC>4 and concentrated under reduced pressure to afford crude tert-butyl (S)-3-methylpiperazine-1-carboxylate (20g, crude yield 100percent) as a yellow liquid. TLC: MeOH : DCM (0.5: 9.5); R,= 0.3., 109-07-9

The synthetic route of 109-07-9 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; ONTARIO INSTITUTE FOR CANCER RESEARCH (OICR); AL-AWAR, Rima; ZEPEDA-VELAZQUEZ, Carlos Armando; PODA, Gennady; ISAAC, Methvin; UEHLING, David; WILSON, Brian; JOSEPH, Babu; LIU, Yong; SUBRAMANIAN, Pandiaraju; MAMAI, Ahmed; PRAKESCH, Michael; STILLE, Julia Kathleen; (1053 pag.)WO2017/147700; (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.2762-32-5,Piperazine-2-carboxylic acid,as a common compound, the synthetic route is as follows.

2-Piperazinecarboxylic acid and 2-chloro-1,3-pyrimidine were stirred with triethylamine and MeOH. After stirring overnight at reflux, the mixture was filtered and concentrated in vacuo to give the desired compound which was used directly in Step B (MH+=209)., 2762-32-5

The synthetic route of 2762-32-5 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; Schering Corporation; US2004/106794; (2004); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

113028-17-4, Ethyl 6-fluoro-1-methyl-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-[1,3]thiazeto[3,2-a]quinoline-3-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,113028-17-4

Example 10: Preparation of prulifloxacin hydrochloride; Method A: To the mixture of dimethylformamide (1.5 It) and 6-fluoro-l-methyl-4-oxo-7-(l- piperazinyl)-lH,4H-[l,3]thiazeto[3,2-a]quinoline-3-carboxylic acid (0.3kg), 4-bromomethyl-5- methyl- 1, 3 -dioxolen-2-one, obtained above was added and cooled to 0-50C. Triethylamine (0.87kg) in dimethylformamide (0.3 It) was added slowly in 1-2 hours. After completion of the reaction (monitored by TLC), dichloromethane (3.0 It) and water (1.5 It) were added to the reaction mixture. The layers were separated and aqueous layer was extracted twice with dichloromethane (1.5 It). All organic layers were combined, dried over sodium sulfate followed by distillation. Methanolic hydrochloride (20-25 % w/w, 0.24 It) was added to organic layer at 0- 5C and stirred. The solid, thus precipitated out was filtered, washed with dichloromethane and dried to obtain 0.36kg of the title compound having purity 92.73 % by HPLC. Example 11: Purification of prulifloxacin hydrochlorideDimethylformamide (1.34 It) was added to prulifloxacin hydrochloride (67g) and reaction mass was heated to 110-112C for 1 hour. The reaction mixture was cooled to 25-300C and stirred for 2 hours, filtered, washed with N,iV-dimethylforamide. The product was slurry washed with isopropanol (0.670 It) and dried to obtain 48.8g of title compound having purity 99.30 % by HPLC.

113028-17-4 Ethyl 6-fluoro-1-methyl-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-[1,3]thiazeto[3,2-a]quinoline-3-carboxylate 10249018, apiperazines compound, is more and more widely used in various fields.

Reference£º
Patent; IND-SWIFT LABORATORIES LIMITED; WO2009/93268; (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.548762-66-9,(2S,5R)-tert-Butyl 2,5-dimethylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

548762-66-9, To a stirred solution of tert-butyl (2S,5R)-2,5-dimethylpiperazine-1-carboxylate (0.35 g, 1.63 mmol) in acetonitrile (8 mL) were added DIPEA (0.9 mL, 4.9 mmol) and methyl 2-bromo-2-(5-(trifluoromethyl)pyridin-2-yl)acetate (0.54 g, 1.79 mmol) at room temperature. The reaction mixture was heated at 85 C for 16 h. The reaction mixture was cooled to room temperature, concentrated under reduced pressure to obtain the crude product, which was purified by silica gel chromatography (24 g; using 6 % -10 % ethyl acetate/ petroleum ether) to obtain tert-butyl (2S,5R)-4-(2-methoxy-2-oxo-1-(5- (trifluoromethyl)pyridin-2-yl)ethyl)-2,5-dimethylpiperazine-1-carboxylate (0.52 g, 74 % yield). LCMS: m/z = 432.2 (M+H); retention time 2.19 min [LCMS method: Column: Waters Acquity UPLC BEH C18 (2.1 x 50 mm), 1.7 mm; Mobile phase A: 0.1% TFA in water; Mobile phase B: 0.1 % TFA in acetonitrile; Gradient = 20-90 % B over 1.1 minute, then a 0.6 minute hold at 90 % B; Temperature: 50 C; Flow rate: 0.7 mL/min; Detection: UV at 220 nm].

The synthetic route of 548762-66-9 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; BRISTOL-MYERS SQUIBB COMPANY; VELAPARTHI, Upender; CHUPAK, Louis S.; DARNE, Chetan Padmakar; DING, Min; GENTLES, Robert G.; HUANG, Yazhong; KAMBLE, Manjunatha Narayana Rao; MARTIN, Scott W.; MANNOORI, Raju; MCDONALD, Ivar M.; OLSON, Richard E.; RAHAMAN, Hasibur; JALAGAM, Prasada Rao; ROY, Saumya; TONUKUNURU, Gopikishan; VELAIAH, Sivasudar; WARRIER, Jayakumar Sankara; ZHENG, Xiaofan; TOKARSKI, John S.; DASGUPTA, Bireshwar; REDDY, Kotha Rathnakar; RAJA, Thiruvenkadam; (0 pag.)WO2020/6018; (2020); 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.692058-21-2,1-Boc-4-(2,2,2-trifluoroethyl)piperazine,as a common compound, the synthetic route is as follows.

692058-21-2, tert-Butyl-l-piperazinecarboxylate (1.00 g, 5.37 mmol) and pyridine (0.868 mL, 10.7 mmol) were combined in methylene chloride (27 mL) and cooled to 0 C. Trifluoroacetic anhydride (0.910 mL, 6.44 mmol) was then added and the reaction mixture was allowed to warm to ambient temperature and stirred 1 h. The reaction mixture was then diluted with ethyl acetate (150 mL) and washed with aqueous potassium hydrogen sulfate (2 x 50 mL), saturated aqueous sodium bicarbonate (50 mL) and brine (50 mL), then dried over sodium sulfate and evaporated to yield tert-butyl 4-(2,2,2-trifluoroacetyl)piperazine-l-carboxylate (1.50 g, 99%) as an oil which solidified over time. tert-Butyl 4-(2,2,2-trifluoroacetyl)piperazine-1-carboxylate (0.908 g, 3.22 mmol) was added to a solution of borane-tetrahydrofuran complex (8 mmol) in tetrahydrofuran (24 mL) and the reaction mixture was heated at reflux for 2 h. After cooling, 2 N hydrochloric acid (4 mL) was carefully added and the reaction mixture was stirred until gas evolution ceased and then diluted with ethyl acetate (200 mL). Aqueous sodium hydroxide (0.2 M, 75 mL) was then added and the phases were separated. The organic layer was dried over sodium sulfate and evaporated. The residue was purified by column chromatography (eluting with 20% ethyl acetate in hexanes) to give tert-butyl 4-(2,2,2-trifluoroethyl)piperazine-1-carboxylate (0.627 g, 73%) as a white solid. A solution of hydrochloric acid (4.0 M, 10 mL) in dioxane was added to a solution of tert-butyl 4-(2,2,2-trifluoroethyl)piperazine-l-carboxylate (0.736 g, 2.74 mmol) in dioxane (5 mL). The reaction mixture was stirred until analysis by thin layer chromatography indicated completion of reaction (approx. 3 h). The volatiles were evaporated and the residue was dried under vacuum to yield 1- (2,2,2-trifluoroethyl)piperazine (0.631 g, 95%) as a white solid.

The synthetic route of 692058-21-2 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; F.HOFFMANN-LA ROCHE AG; WO2005/110996; (2005); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

163765-44-4, (R)-1-Boc-3-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

The compound (R) -4-Boc-2- methylpiperazine (528mg, 2.64mmol), glacial acetic acid (190mg, 3.16mmol), 1-ethyl-3- (3- Dimethylaminopropyl) carbodiimide hydrochloride (758mg, 3.95mmol) and N- hydroxy-7-azabenzotriazole(897mg, 6.59mmol) was dissolved In dichloromethane (20 mL), and under conditions of 0 C tothis solution was added dropwise N, N- diisopropylethylamine (1.8mL, 10.54mmol), stirred at roomtemperature Stirred 12h, was added water (10mL ¡Á 2) washing the organic phase was dried over anhydrous Na 2SO 4, the solvent was removed concentrate was separated by column chromatography (leaching Lotion: DCM /MeOH (v / v) = 40/1), to give 580mg colorless oil: Compound N- acetyl-4-tert-butoxycarbonyl -2- (R) – methylPiperazine, yield: 90%., 163765-44-4

The synthetic route of 163765-44-4 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; Guangdong East Sunshine Pharmaceutical Co., Ltd; Zhang, Ying jun; Liu, Bing; Yu, Tian Zhu; Zhang, Xiang Yu; (348 pag.)CN105399698; (2016); A;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics