Heterocyclic Building Blocks-piperazine

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.5464-12-0,1-(2-Hydroxyethyl)-4-methylpiperazine,as a common compound, the synthetic route is as follows.

10.0 g 2-chloro-3 -methyl-4-(4,4, 5,5 -tetramethyl- 1,3 ,2-dioxaborolan-2-yl)phenol(Preparation 5a) (37.2 mmol), 8.7 g 2-(4-methylpiperazin-1-yl)ethanol (60.3 mmol) and15.8 g PPh3 (60.3 mrnol) were dissolved in 100 mL dry toluene and then 27 mL diethylazodicarboxylate (60.3 mmol, 40percent solution in toluene) was added dropwise. The mixturewas stirred at 50°C under argon for 1.5 hours. The volatiles were evaporated under reducedpressure and 100 rnL Et20 was added. The precipitated white crystals were filtered off and washed with Et20. The filtrate was concentrated under reduced pressure and pudfied via flash chromatography using CHC13 and MeOH as eluents. The resulting light brown oil was crystallized from hexanc to give Preparation Sb as an off-white solid.?11 NMR (500 MHz, DMSO-d6): 7.56 (d, 111), 6.99 (d, 1H), 4.15 (t, 2H), 2.72 (t, 2H), 2.51 (s, 311), 2.50 (br s, 4H), 2.29 (br s, 411), 2.13 (s, 311), 1.29 (s, 12H)., 5464-12-0

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; KOTSCHY, Andras; SZLAVIK, Zoltan; CSEKEI, Marton; PACZAL, Attila; SZABO, Zoltan; SIPOS, Szabolcs; RADICS, Gabor; PROSZENYAK, Agnes; BALINT, Balazs; BRUNO, Alain; GENESTE, Olivier; DAVIDSON, James Edward Paul; MURRAY, James Brooke; CHEN, I-Jen; PERRON-SIERRA, Francoise; WO2015/97123; (2015); A1;,
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With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.122323-88-0,Methyl piperazine-2-carboxylate dihydrochloride,as a common compound, the synthetic route is as follows.,122323-88-0

REFERENCE EXAMPLE 2 A solution of 3,4,5-trimethoxybenzoyl chloride (10.9 g) in dichloromethane (100 ml) is added dropwise taking one hour, under ice-cooling while stirring, to a mixture of methyl piperazine-2-carboxylate dihydrochloride (10.24 g), triethylamine (18.7 g) and dichloromethane (200 ml). The reaction mixture is poured into ice-water, followed by extraction with dichloromethane. The organic layer is washed with water, dried and the solvent is distilled off under reduced pressure. Crystals obtained from the residue are recrystallized from ethyl acetate and hexane to afford methyl 4-(3,4,5-trimethoxybenzoyl)piperazine-2-carboxylate (9.6 g) as colorless needles, m.p. 113-114 C.

The synthetic route of 122323-88-0 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Takeda Chemical Industries, Ltd.; US4997836; (1991); A;,
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Piperazines – an overview | ScienceDirect Topics

262368-30-9, N-(4-Aminophenyl)-N-methyl-2-(4-methylpiperazin-1-yl)acetamide is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

A solution of methyl (Z)-3-(chloro(4-(hydroxymethyl)phenyl)methylene)-2-oxoindoline- 5-carboxylate (17 mg, 0.05 mmol), N-(4-aminophenyl)-N-methyl-2-(4-methylpiperazin-1-yl)acetamide (15 mg, 0.06 mmol) and TEA (0.1 muL, 0.10 mmol) in EtOH (0.1 muL) was stirred under refluxed for overnight. The reaction solvent was evaporated under reduced pressure, and the residue was purified by column chromatography with dichloromethane/ethanol (50/1, v/v) to obtain the final compound 100 (15 mg, 52% yield): 1H NMR (500 MHz, DMSO-d6) _ 11.97 (s, 1H), 11.13 (s, 1H), 7.57 (d, J = 8.2 Hz, 1H), 7.51 (d, J = 7.8 Hz, 2H), 7.44 (d, J = 7.8 Hz, 2H), 7.13 (d, J = 8.2 Hz, 2H), 6.93 (d, J = 8.3 Hz, 1H), 6.90 (d, J = 8.2Hz, 2H), 6.51 (s, 1H), 5.49 (bs, 1H), 4.64 (s, 2H), 3.63 (s, 3H), 3.05 (bs, 2H), 2.69 (bs, 2H), 2.18 (bs, 6H), 2.10 (s, 3H); 13C NMR (125 MHz, DMSO-d6) _ 170.4, 168.6, 166.4, 157.2, 145.0, 140.4, 139.8, 130.3, 128.3, 127.8, 127.7, 127.0, 125.5, 124.0, 123.6, 121.3, 119.6, 108.8, 97.6, 62.4, 59.2, 54.6, 52.5, 52.4, 51.6, 51.5, 45.8, 36.7; HRMS (ESI-TOF) m/z calcd for C31H32N6O6 [M + H+] 569.2638 found 570.2713.

262368-30-9, The synthetic route of 262368-30-9 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM; DALBY, Kevin N.; EDUPUGANTI, Ramakrishna; TALIAFERRO, Juliana; LEE, Juhyeon; (0 pag.)WO2018/160967; (2018); A1;,
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74879-18-8, (S)-(+)-2-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

74879-18-8, Intermediate 16 (3S)-3-Meth l-1 -{[4-(trifluoromethyl)phenyl]sulfonyl}piperazine(2S)-2-Methylpiperazine (15 g, 150 mmol) was dissolved in tetrahydrofuran (300 mL) and the solution was cooled down to 0C. Sodium hydroxide (150 mL, 449 mmol) was added, then 4-(trifluoromethyl)benzenesulfonyl chloride (40 g, 164 mmol) (dissolved in 200ml THF) was added dropwise and the resulting mixture was stirred for 1 h. Further 4-(trifluoromethyl)benzenesulfonyl chloride (0.06eq , 2.2g) was added and mixture stirred for 10 min. The mixture was diluted with DCM (500ml) and water (500ml) and stirred for 5 min. The phases were separated, the aqueous layer was extracted with DCM (1000ml) and the organic phases concentrated under reduced pressure. The residue was taken-up with 1 M HCI (500ml) and washed with DCM in order to extracted impurities. The aqueous phase was basified to pH=9 with NaOH 3M, extracted with DCM ( 3x 500ml) and the combined organic phases dried over Na2S04 before the solvent was removed under reduced pressure to give the title compound (30 g).LCMS (low pH) m/z (ES) 309 [M+H]+ 1 H NMR (400 MHz, CDCI3) delta 1 .06 (d, J = 7.2 Hz, 3H), 1.94 (t, J = 10.4 Hz, 1 H), (td, J = 1 1 .2, 4.0 Hz, 1 H), 2.88-3.07 (m, 3H), 3.66 (m, 2H), 7.83 (d, J = 8.4 Hz, 2H), 7.90 (d, J = 8.4 Hz, 2H) ppm

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

Reference：
Patent; CONVERGENCE PHARMACEUTICALS LIMITED; HEER, Jag Paul; CRIDLAND, Andrew Peter; NORTON, David; WO2011/86377; (2011); A1;,
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928025-56-3,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.928025-56-3,(S)-tert-Butyl 3-ethylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

Example 161a (S)-tert-Butyl 3-Ethyl-4-(6-nitropyridin-3-yl)piperazine-1-carboxylate 161a A 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 1,4-dioxane (50 mL), 5-bromo-2-nitropyridine (2.02 g, 10 mmol), (S)-tert-butyl 3-ethylpiperazine-1-carboxylate (2.14 g, 10.0 mmol), Pd2(dba)3 (458 mg, 0.50mmol), XantPhos (576 mg, 1.0 mmol), and cesium carbonate (6.52 g, 20 mmol). After three cycles of vacuum/argon flush, the mixture was heated at 100C overnight. After this time the reaction was cooled to room temperature. It was then filtered and the filtrate was evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 3:1 petroleum ether/ethyl acetate to afford 161a (700 mg, 22%) as a yellow solid. MS: [M+H]+ 336

As the paragraph descriping shows that 928025-56-3 is playing an increasingly important role.

Reference：
Patent; F.Hoffmann-La Roche AG; CRAWFORD, James John; ORTWINE, Daniel Fred; WEI, BinQing; YOUNG, Wendy B.; EP2773638; (2015); B1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

13484-40-7, 1-(2-Methoxyethyl)piperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To a solution of 2-chloro-4-morpholinothieno[3,2-i/]pyrimidine-6- carbaldehyde (150 mg, 0.5 mmol) in 1,2-dichloroethane (2.5 mL) was added l-(2- methoxyethyl) piperazine (110 muL , 0.7 mmol) and AcOH (30 muL, 0.5 mmol). After stirring 10 min at room temperature, Na(OAc)3BH (130 mg, 0.6 mmol) was added and the resulting mixture stirred overnight. The reaction was quenched by the addition of saturated aqueous NaHCO3 and the organic layer was separated. The aqueous layer was extracted with CH2Cl2 and the combined organics were dried over Na2SO4, filtered, and concentrated in vacuo. The resulting crude mixture was coupled using General Procedure A with 5-(4,4,5,5-tetramethyl- l,3,2-dioxaborolan-2-yl)pyrimidin-2-amine to provide 137 after reverse phase HPLC purification (43 mg). MS (Ql) 471 (M)+., 13484-40-7

As the paragraph descriping shows that 13484-40-7 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.109-01-3,1-Methylpiperazine,as a common compound, the synthetic route is as follows.,109-01-3

A mixture of 3-bromopropanol (20 ml), N-methylpiperazine (29 ml), potassium carbonate (83 g) and ethanol (200 ml)was stirred and heated to reflux for 20 hours. The mixture was cooled to ambient temperature and filtered. The filtrate was evaporated and the residue was triturated under diethyl ether. The resultant mixture was filtered and the filtrate was evaporated. The residue was purified by distillation at about 60-70 C. under about 0.2 mm Hg to give 1-(3-hydroxypropyl)-4-methylpiperazine (17 g); NMR Spectrum: (CDCl3) 1.72 (m, 2H), 2.3 (s, 3H), 2.2-2.8 (m, 8H), 2.6 (t, 2H), 3.8 (t, 2H), 5.3 (br s, 1H).

The synthetic route of 109-01-3 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; AstraZeneca AB; US2004/48881; (2004); A1;; ; Patent; Lambert, Christine Marie Paul; Ple, Patrick; US2004/44015; (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.112984-60-8,6-Fluoro-1-methyl-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid,as a common compound, the synthetic route is as follows.

Example 1 Preparation of (S)-(-)-uliflourxacin; 105 g of racemic uliflourxacin was dissolved in 1,500 mL of dimethyl sulfoxide. 27 g of D-tartaric acid was dissolved in 405 mL of dimethyl sulfoxide dropwise while stirring. After stirring at room temperature for 20 hours, the precipitate was filtrated. The collected solid was dried under vacuum to obtain 86 g solid, which was recrystallized in dimethyl sulfoxide to obtain 37 g of levoulifloxacin-D-tartrate, with C49.08%, H5.06%, N9.50%, S7.44% shown by elemental analysis (molecular formula: C16H16FN3O3S·1/2C4H6O6·H2O, calculated values: C48.86%, H4.78, N9.50%, S7.25%). Said salt was added into water to obtain a suspension, and the pH value was adjusted to 7-8 with 2% NaOH aqueous solution while stirring. After precipitation, filtration, and drying, 24.5 g of (S)-uliflourxacin was obtained, having a chemical name (S)-(-)-6-fluoro-1-methyl-4-oxo-(1-piperazinyl)-1H,4H-[1,3]thiazeto [3,2-alpha]quinoline-3-carboxylic acid. Specific rotation [alpha]20D= -133 (c=0.5, 0.1 mol/L methanesulfonic acid); 1H-NMR (DMSO-d6) delta2.11 (3H, d, j=6.2 Hz), 2.87 (4H, m), 3.19 (4H, m), 6.40 (1H, q, j=6.2 Hz), 6.89 (1H, d, j=7.4Hz), 7.79 (1H, d, j=13.9Hz), optical purity e.e. 96%.

112984-60-8, 112984-60-8 6-Fluoro-1-methyl-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid 124225, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; Hainan Hualon Pharmaceutical Co., Ltd.; EP2524922; (2012); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

103-76-4, N-(2-Hydroxyethyl)piperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

An electrically-heated, mechanically stirred 1 liter autoclave was fitted with an vent valve connected in turn to a condenser and receiver assembly, a bottom valve, a thermowell, a pressure gauge, an inlet line for feeding of reagents, and a pressure-relief valve. The receiver was placed on a balance to facilitate continuous determination of the amount of distillate collected in the receiver. The amine starting material, aqueous sodium 2-hydroxyethanesulfonate, and aqueous 50 percent sodium hydroxide were charged to the autoclave. With the isolation valve open, the reaction mixture was rapidly heated with stirring until condensate was detected in the condenser/receiver. The mixture was further heated with continuous removal of water until the targeted amount of distillate had been removed. An analysis of the collected aqueous distillate was performed by UV spectroscopy to determine the amount of amine which co-distilled with the water. The isolation valve was then closed and the reaction mixture further heated to a target temperature in the range of 140-200 C. for 2-17 hours as specified in Examples 1-8. The reaction mixture was then cooled until the pressure dropped to 0 psig (ca. 110 C.) whereupon dilution water was added to dilute the concentrated reaction product. The resulting solution was then cooled to room temperature and drained from the reactor. Analysis of the product mixture was then performed by various chromatographic and spectroscopic procedures as indicated in the specific examples.; Procedure C A magnetically-stirred 70-mL fluoropolymer-lined steel autoclave was fitted with an internal thermocouple capable of determining the temperature of the liquid phase contained in the vessel, a pressure gauge, a pressure-relief valve, and a vent valve. The amine starting material, anhydrous or aqueous sodium 2-hydroxyethanesulfonate, and anhydrous or aqueous sodium hydroxide were charged to the open autoclave, which was then assembled and immersed in an electrically heated oil bath. With the vent valve closed, the stirred reaction mixture was rapidly heated to the reaction temperature and held at that temperature for the times specified in Examples 9, 10, and 13 below. The reaction mixture was then cooled to ambient temperature, the reactor opened, and the reaction product taken up in sufficient water to dissolve all solids., 103-76-4

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

Reference：
Patent; Carroll, Glenn T.; Smith, Gary S.; Stringer, Gary E.; US2006/89509; (2006); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

1001180-21-7, (R)-tert-Butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Step 9: Triethylamine (4.33 ml, 31.1 mmol; degassed with nitrogen 30 minutes prior to use) and formic acid (1.36 ml, 36.1 mmol; degassed with nitrogen 30 minutes prior to use) were added to a solution of (R)-tert-butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H- cyclopenta[d]pyrimidin-4-yl)piperazine-l-carboxylate (9.75 g, 29.3 mmol) in DCM (210 mL; degassed with nitrogen 30 minutes prior to use). The mixture was stirred for 5 minutes, then a Ru catalyst (0.0933 g, 0.147 mmol) was added. The reaction was stirred under positive nitrogen pressure overnight (18 hours). The reaction mixture was concentrated to dryness and dried on high vacuum. The impure material was flashed on Biotage 65M loaded 1 : 1 DCM:ethyl acetate 500 mL flushed, then 1 :4 DCM:ethyl acetate until product (2nd spot), then gradient to neat ethyl acetate, then 25:1 DCM:MeOH eluted rest of product. The fractions were combined and concentrated on a rotary evaporator. The residue was concentrated again from DCM/hexanes to give a mixture of tert-butyl 4-((5R,7R)-7-hydroxy- 5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine- 1 -carboxylate (major) and tert-butyl 4-((5R,7S)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4- yl)piperazine-l -carboxylate (minor) (9.35 g, 95.3% yield) as a beige foam. LC/MS (APCI+) m/z 335 [M+H]+. 1H NMR (CDC13) shows 88% de by integration of carbinol methine., 1001180-21-7

1001180-21-7 (R)-tert-Butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate 59580350, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; GENENTECH, INC.; HOEFLICH, Klaus; MERCHANT, Mark; WO2012/135750; (2012); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics