Category: piperazines

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.122833-04-9,2-Methoxy-4-(4-methylpiperazin-1-yl)aniline,as a common compound, the synthetic route is as follows.

To a solution of (R)-2,5- dichloro-N-((tetrahydrofuran-2-yl)methyl)pyrimidin-4-amine (Lawrence, H. R.; et al. (2015) Development of Novel ACK1/TNK2 Inhibitors Using a Fragment Based Approach. /. Med. Chem. 58 (6), 2746-2763) (0.100 g, 0.403 mmol) and 2-methoxy-4-(4-methylpiperazin-l- yl)aniline (98 mg, 0.443 mmol) in 2-methoxyethanol (2 mL) was added 4 M HC1 in dioxane (0.110 mL, 0.443 mmol). The solution was stirred and heated at 110 C for 18 h. Then, the mixture was concentrated under reduced pressure and partitioned between saturated NaHCCb and CHCb (20 mL each). The aqueous layer was re-extracted with CHCb (20 mL). The organic layers were combined, dried (Na2S04), filtered, and concentrated under reduced pressure. The resulting crude mixture was purified by flash chromatography (S1O2) eluting with DCM in MeOH (0% to 10%) to provide the title compound as a brown oil (79 mg, 54%). HPLC: 95% [tR = 6.8 min, 30% MeOH, 70% water (with 0.1% TFA), 20 min. lH NMR (400 MHz, DMSO-ifc): delta 7.84 (s, 1H), 7.78 (d, / = 8.8 Hz, 1H), 7.45 (s, 1H, disappeared on D20 shake), 7.00 (t, / = 6.0 Hz, 1H, disappeared on D20 shake), 6.59 (d, / = 2.6 Hz, 1H), 6.42 (dd, / = 8.8, 2.6 Hz, 1H), 4.03 (pentet, / = 6.0 Hz, 1H), 3.79 (s, 3H), 3.76-3.69 (m, 1H), 3.62-3.56 (m, 1H), 3.36 (t, / = 6.0 Hz, 2H), 3.10-3.04 (m, 4H), 2.46-2.40 (m, 4H), 2.20 (s, 3H), 1.90-1.71 (m, 3H), 1.60-1.50 (m, 1H). HPLC-MS (ESI+): m/z 433.2 [30%, (M35C1+H)+], 218.2 [40%, (M37C1+2H)2+], 217.2 [100%, (M35C1+2H)2+]. LC-MS (ESI+): 433.2 [100%, (M35C1+H)]. HRMS (ESI+): m/z calcd for C21H29CIN6O2 (M+H)+ 433.2113, found 433.2106., 122833-04-9

The synthetic route of 122833-04-9 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; H. LEE MOFFITT CANCER CENTER & RESEARCH INSTITUTE; MAHAJAN, Nupam P.; MAHAJAN, Kiran N.; LAWRENCE, Nicholas J.; LAWRENCE, Hirshani R.; (85 pag.)WO2017/23899; (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.76003-29-7,1-Boc-3-Oxopiperazine,as a common compound, the synthetic route is as follows.

a) A solution of (2-bromoethoxy)-tert-butyldimethylsilane (4.71 g, 19.7 mmol) in tetrahydrofuran (20 ml) was added dropwise at room temperature to a stirred solution of tert- butyl 3-OXOPIPERAZINE-1-CARBOXYLATE (3.94 g, 19.7 mmol), powdered potassium hydroxide -183- (1.32 g, 23.6 mmol) and tetrabutylammonium bromide (1.27 g, 3.94 mmol) in tetrahydrofuran (30 ml) and the resulting mixture was stirred for 4 hours. The mixture was filtered and then evaporated to leave a colourless viscous oil which was purified by silica gel chromatography eluting with methyl tert-butyl ether as eluent to give tert-butyl 4-(2-{[TERT- butyl (dimethyl) silyl] OXY} ETHYL)-3-OXOPIPERAZINE-1-CARBOXYLATE (3.42 g, 45% yield) as a colourless oil: 1H-NMR (CDC13): 4.08 (s, 2H), 3.80 (t, 2H), 3.61 (m, 2H), 3.50 (m, 4H), 1.46 (s, 9H), 0.87 (s, 9H), 0.05 (s, 6H)., 76003-29-7

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

Reference：
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2004/94410; (2004); 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

A solution of triphenylphosphane (31.7966 mg, 0.121 mmol) in 1 : 1 DCM:THF (0.6 mL) was cooled to 0°C and treated with diisopropyl azodicarboxylate (0.023 mL, 0.121 mmol) and stirred at 0°C for 15 min. The reaction mixture was treated with 6-hydroxy-4-(6-(4- (pyridin-2-yloxy)piperidin-l-yl)pyridin-3-yl)pyrazolo[l,5-a]pyridine-3-carbonitrile(Intermediate P78, 25.0 mg, 0.0606 mmol) in a 1 : 1 DCM:THF (0.6 mL) and 1-(N- hydroxyethyl)-4-methyl piperazine (13.1 mg, 0.0909 mmol). The reaction mixture was allowed to warm to rt and was stirred at this temperature for 30 min. The reaction mixture was concentrated in vacuo, and the resultant crude residue was directly purified by C-18 reverse phase chromatography (5-95percent ACN in water [+ 0.1percent TFA] as the gradient eluent). The fractions containing the desired product were diluted with 4: 1 DCMTPA and washed with saturated NaHC03(aq). The organic extract was dried over anhydrous Na2S04(S), filtered, and concentrated in vacuo to afford the title compound (31.5 mg, 0.0526 mmol, 86.8percent yield). MS (apci) m/z = 539.2 (M+H).

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

Reference：
Patent; ANDREWS, Steven W.; ARONOW, Sean; BLAKE, James F.; BRANDHUBER, Barbara J.; COLLIER, James; COOK, Adam; HAAS, Julia; JIANG, Yutong; KOLAKOWSKI, Gabrielle R.; MCFADDIN, Elizabeth A.; MCKENNEY, Megan L.; MCNULTY, Oren T.; METCALF, Andrew T.; MORENO, David A.; RAMANN, Ginelle A.; TANG, Tony P.; REN, Li; WALLS, Shane M.; (946 pag.)WO2018/71454; (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.55121-99-8,(4-Aminophenyl)(4-methylpiperazin-1-yl)methanone,as a common compound, the synthetic route is as follows.

55121-99-8, Example No. 134Preparation of (4-methylpiperazin-l-yl) (4- ( (5- (thiophen-2-yl) – IH-pyrazolo [4 , 3 -d] pyrimidin-7-yl) amino) phenyl) methanone7-chloro-2- (4-methoxybenzyl) -5- (thiophen-2-yl) -2H- pyrazolo [4 , 3 -d] yrimidine (0.16 mmol) and (4 -aminophenyl) (4- methylpiperazin-l-yl) methanone (0.3 mmol 2 eq. , ) were suspended in MeOH (dry, 3mL) in a microwave vial (2-5mL) , HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3mL) . The reaction mixture was irradiated in a microwave reactor for 5 min at 140C. The reaction mixture was concentrated and purified by semi -preparative HPLC-MS and freeze dried from water/t-BuOH 4/1. exact mass: 419.1830 g/molHPLC-MS: analytical method Crt: 1.97 min – found mass: 420 (m/z+H)

55121-99-8 (4-Aminophenyl)(4-methylpiperazin-1-yl)methanone 231408, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; ORIGENIS GMBH; ALMSTETTER, Michael; THORMANN, Michael; TREML, Andreas; TRAUBE, Nadine; WO2012/143144; (2012); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

132710-90-8, 1-Boc-4-(3-hydroxypropyl)piperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Sodium hydride (12.5 mg, 0.3141 mmol) was added to a solution of tert-butyl 4-(3- hydroxypropyl)piperazine-1-carboxylate (154-1) (76.7 mg, 0.3141 mmol) in DMF (2.09 mL ) at 0 C. The bath was removed and the reaction stirred for 30 min. 6-(4-chlorophenyl)-8-(1-(3- chloropropyl)-1H-pyrazol-4-yl)-1-methylspiro[benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine-4,1′- cyclopropane] (89-1) (0.1 g, 0.2094 mmol) was added, the reaction stirred for 16 hours and concentrated. The product was purified by column chromatography (silica, 0-15% MeOH in DCM) to give tert-butyl 4-(3-(3-(4-(6-(4-chlorophenyl)-1- methylspiro[benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine-4,1′-cyclopropan]-8-yl)-1H-pyrazol-1- yl)propoxy)propyl)piperazine-1-carboxylate (154-2) (22.0 mg, 15.3 %) LC/MS (ES+): m/z 685.3 [M + H]+

132710-90-8, As the paragraph descriping shows that 132710-90-8 is playing an increasingly important role.

Reference：
Patent; C4 THERAPEUTICS, INC.; PHILLIPS, Andrew, J.; NASVESCHUK, Chris, G.; HENDERSON, James, A.; LIANG, Yanke; FITZGERALD, Mark, E.; MICHAEL, Ryan, E.; (790 pag.)WO2017/197056; (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.13889-98-0,1-Acetylpiperazine,as a common compound, the synthetic route is as follows.

4-Fluorobenzaldehyde15 (619 muL, 5.85 mmol), 1-acetylpiperazine (500 muL, 3.90 mmol) and Na2CO3 (620 mg, 5.85mmol) were dissolved in H2O (25 mL) and the stirred at 100C overnight. After extractionwith DCM, the combined organic layers were concentrated under reduced pressure and silicagel column chromatography (3% MeOH/DCM) yielded 17a (942 mg, 58%). 1H NMR (500MHz, DMSO-d6) delta 9.73 (s, 1H), 7.73 (d, J = 8.9 Hz, 2H), 7.04 (d, J = 8.9 Hz, 2H), 3.65-3.54 (m,4H), 3.50-3.44 (m, 2H), 3.42-3.36 (m, 2H), 2.04 (s, 3H); 13C NMR (126 MHz, DMSO-d6) delta190.2, 168.42, 154.3, 131.4, 126.4, 113.2, 46.3, 46.0, 44.9, 40.3, 21.1; HRMS (ESI-MS): Calculatedfor C13H17N2O2 [M+H]+: 233.12845; found: 233.12871.

13889-98-0, 13889-98-0 1-Acetylpiperazine 83795, apiperazines compound, is more and more widely used in various fields.

Reference：
Article; Buehrmann, Mike; Wiedemann, Bianca M.; Mueller, Matthias P.; Hardick, Julia; Ecke, Maria; Rauh, Daniel; PLoS ONE; vol. 12; 9; (2017);,
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

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

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

1235865-77-6, 2-((1H-Pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To a solution of 2-(lH-pyrrolo[2,3-b]pyridine-5-yloxy)-4-(4-((2-4-chlorophenyl)-4,4- dimethylcyclohex-l-enyl)methyl)piperazin-l-yl)benzoic acid (100 g) in MDC (1500 ml) were added 3-nitro-4-((tetrahydro-2H-pyran-4yl)methylmaino)benzenesulfonamide (71.78 g),DMAP(6.4l g) and EDCI. HC1 (61.16 g) at room temperature and stirred till completion of reaction. After completion of reaction, water was added to the reaction mixture, stirred for 30 minutes and filtered at room temperature. The filtrate was stirred for 30 mins at room temperature and layers were separated. The organic layer (MDC) was distilled atmospherically below at 55 C to obtain residue (diamide content 5%). To residue methanol (1000 inL) was added and temperature was raised to 50-70C and solvent (100 mL) was distilled. To the reaction mass, sodium Hydroxide (10.50 g) solution in methanol was added at 55-60C and stirred for 2 hrs. Reaction mixture was cooled to 40-45C, stirred for 45 mins and filtered. Wet cake was washed with methanol (200 ml). Obtained compound was added to dimethylformamide (300 mL), heated at 50-60C and stirred for 30-50 mins to get clear solution. Methanol (300 mL) was added to the solution at 50-60C and stirred for 30-50 mins. Reaction mixture was cooled to 25- 35C and stirred for 8hrs.The reaction mixture was filtered and solid was washed with mixture of DML: Methanol (1 :3) (100 mL). Wet cake was dried at 25-35C for 1 hr in VTD to obtain sodium salt of Venetoclax (Form AL2 of Venetoclax) 80-90 g. (>53% yield) (diamide content > 0.3% ).1H NMR (300 MHz, Dimethyl sulfoxide d6) 11.53 (br s, 1H), 8.42(br s, 1H), 8.34(t, 1H), 7.95(d, 1H), 7.64(t, 2H), 7.27-7.4l(m, 4H), 6.62-6.78(dd, 2.02), 6.29-6.30(br s, 2H), 3.83-3.88(d, 2H), 3.42(br s, 4H), 3.l9-3.29(m, 6H), 3.0l(br s, 4H), 2.89(s, 1H), 2.74-2.72(m, 3H), 2.20(br s, 6 H), l.95-l.23(m, 9H), 0.92(s, 6H).13C NMR:-l70.89, 156.59, 153.06, 149.85, 146.21, 145.00, 142.54, 135.25, 134.99, 134.45, 133.52, 132.57, 131.26, 130.49, 129.66, 129.61, 128.51, 127.37, 125.48, 123.54, 120.02, 116.22, 113.97, 109.76, 106.55, 100.05, 67.13, 60.27, 52.80, 49.09, 48.31, 47.93, 46.78, 36.25, 35.32, 34.34, 31.24, 30.70, 29.33, 28.37., 1235865-77-6

1235865-77-6 2-((1H-Pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid 66713100, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; ALEMBIC PHARMACEUTICALS LIMITED; TVSK, Vittal; CHUDASAMA, Dinesh; DONTHUKURTHI, Saisuryanarayana; SHAH, Tejas; PATIL, Chetan; VELISOJU, Mahendar; SIRIPRAGADA, Mahender Rao; (28 pag.)WO2019/150253; (2019); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics