Month: June 2021

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.142-64-3,Piperazine Dihydrochloride,as a common compound, the synthetic route is as follows.

100 g (1.2 mol) of anhydrous piperazine and 240 g (1.5 mol) of piperazine dihydrochloride were heated to 120 C, and 150 g (1.2 mol) of 2-(2-chloroethoxy)ethanol was added dropwise. After the completion of heating and stirring, the temperature was raised to 136-140 C for 1 hour, and TLC showed that the reaction was completed and then the heating was stopped. When the temperature dropped to 80 degrees Celsius, 500ml of 95% ethanol was added, cooled in the refrigerator overnight, and the piperazine dihydrochloride was recovered by filtration the next day. The filter cake was washed thoroughly with a small amount of ethanol, the filtrate was combined, and 200 g of 30% sodium hydroxide solution was added, alkalized, and the insoluble inorganic salt was filtered off, and concentrated to remove the solvent. The residue was extracted with ethyl acetate, dry hydrogen chloride gas was passed, filtered and dried to give a white solid 1-[2-(2-hydroxyethoxy)ethyl]piperazine hydrochloride. The solid content was already above 98%. After recrystallization from a 90% aqueous solution of ethanol, 207 g of white crystals can be obtained, the yield was 70%, and the content can be more than 99.5%., 142-64-3

The synthetic route of 142-64-3 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Wuxi Qianhao Bio-pharmaceutical Co., Ltd.; Peng Haiyan; (4 pag.)CN109400549; (2019); A;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

31166-44-6, 1-Cbz-Piperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

(0937) [00331] Into a 100-mL round-bottom flask, purged and maintained under an inert atmosphere of nitrogen, was added fe/t~buty (4~bromophenethyl)carbarnate (4.00 g, 13.3 mmol) dissolved in anhydrous toluene (50-mL). To the resulting solution was added benzyl piperazine-1- carboxylate (3.53 g, 16.0 mmol), Pd(OAc)2 (0.300 g, 1.34 mmol), XPhos (1.28 g, 2.69 mmol), and CS2CO3 (13.1 g, 40.0 mmol). The reaction mixture was stirred overnight at 105 °C in an oil bath and then cooled to RT and quenched with H2O (200 mL). The resulting mixture was extracted with ethyl acetate (2 x 50 mL). The combined organic layers were washed with brine (1 x 200 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The resulting crude product was purified by FCC eluting with ethyl acetate/petroleum ether (PE/EA=3: 1) to afford benzyl 4-(4-(2-((feri-butoxycarbonyl)amino)ethyl)phenyl) piperazine-1- carboxylate as a yellow solid (5 g, 85percent), LCMS (ESI, m/z): 440 [M+H]+., 31166-44-6

31166-44-6 1-Cbz-Piperazine 643495, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; FORMA THERAPEUTICS, INC.; GUERIN, David Joseph; BAIR, Kenneth W.; CARAVELLA, Justin A.; IOANNIDIS, Stephanos; LANCIA JR., David R.; LI, Hongbin; MISCHKE, Steven; NG, Pui Yee; RICHARD, David; SCHILLER, Shawn E. R.; SHELEKHIN, Tatiana; WANG, Zhongguo; (365 pag.)WO2017/139778; (2017); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

13754-38-6, 1-Benzoylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

General procedure: A mixture of compounds 11 (2.74 g, 10 mmol), amine 12(11 mmol), and K2CO3 (1.66 g, 12 mmol) in CH2Cl2 (10 ml) wereheated at 40 C for 0.5 h. The progress of the reaction was monitoredby TLC, after completion of the reaction, the reaction mixturewas extracted with three portions of CH2Cl2. The orange extractswere washed with brine until neutrality, then dried over anhydrousNa2SO4 and concentrated in vacuo. Then the residue waspurified by a silica-gel column chromatography (PE/EtOAc 3:1) togive the desired compounds.

13754-38-6, As the paragraph descriping shows that 13754-38-6 is playing an increasingly important role.

Reference：
Article; Wang, Jin; Xia, Fei; Jin, Wen-Bin; Guan, Jin-Yan; Zhao, Hang; Bioorganic Chemistry; vol. 68; (2016); p. 214 – 218;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

109-01-3, 1-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

A/Preparation of N-(2-hydroxyethyl)-N’-methylpiperazine: N-methylpiperazine (10 g; 100 mmol) and 2-chloroethanol (8.05 g; 100 mmol) are stirred at 100° C. for 4 h. The highly viscous reaction medium is supplemented with 250 ml of acetone and the resulting suspension is neutralized with 15 ml of triethylamine. After filtration of the triethylamine hydrochloride, the solvent is evaporated under reduced pressure. The desired compound is obtained after purification by chromatography on an alumina column (Merck.(R).; Aluminum Oxide 90; 63-200 mum, eluent: ethyl acetate) in the form of a colorless oil. Yield: 75percent

109-01-3, As the paragraph descriping shows that 109-01-3 is playing an increasingly important role.

Reference：
Patent; Oxis Isle of Man, Limited; US6056965; (2000); A;,
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.54699-92-2,4-Methyl-1-piperazineacetic acid,as a common compound, the synthetic route is as follows.

54699-92-2, Example 13; General Method For The Preparation Of Active Esters Of N-Substituted Piperazine Acetic Acid From Trifluoroacetate Esters; A solution of the trifluoroacetate in THF (0.58 M, 1.2 equiv) was added to a solid sample of N-methyl piperazine acetic acid and mixed in a vortex or shaker until a homogeneous solution was obtained. The reaction of the carboxylic acid with the trifluoroacetate ester was generally complete within 30 min for all cases except N-hydroypyrrolidinone (NHP, 18 h). The progress of conversion to the active ester was monitored by ES-MS. The amount of product and any starting material (N-MPA) could be determined by direct infusion of a sample of the reaction (in ethanol) into the ES-MS. In some cases the active ester product was precipitated as dihydrochloride salt by the addition of a solution by addition of HCl solution in dioxane (4 M, 50% volume of the reaction) followed by washing with THF, ethyl acetate and hexanes. In other cases the product was isolated from the reaction as the mono TFA salt. Addition of TFA could be performed if the bis-TFA salt was desired. Dhbt ester, Calculated MH+ = 304.14 Found = 304.20 NHP ester, Calculated MH+ = 242.15 Found = 242.20 4-NP ester, Calculated MH+ = 280.13 Found = 280.20 1H NMR (400 MHz, CDCl3) d 8.20 (d, 2H, J=9.2 Hz, aromatic protons), 7.25 (d, 2H, J=9.2 Hz, aromatic protons), 3.69-3.40 (broad, 2H, ring protons), 3.57 (s, 2H, -CH-CO-), 3.15-2.90 (broad, 6H, ring protons), 2.78 (s, 3H, -CH3). Pfp ester, Calculated MH+ = 325.10 Found = 325.10 Pcp ester, Calculated MH+ = 404.95 Found = 405.90 3-NP ester, Calculated MH+ = 280.13 Found = 280.20 NHS ester, Calculated MH+ = 256.13 Found = 256.10

54699-92-2 4-Methyl-1-piperazineacetic acid 2762732, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; Applera Corporation.; US2005/148773; (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.34770-60-0,4-Methylpiperazin-2-one,as a common compound, the synthetic route is as follows.

General procedure: 6.1.15. General procedure IV, for preparation of 14a-f A mixture of aryl bromide (1.0 mmol), 4-methylpiperazin-2-one (for compounds 15-17)/morpholin-3-one (for compounds 18-20) (2.0 mmol), N,N0-dimethylethylene diamine (0.1 mmol), K2CO3 (2.0 mmol) and CuI (0.05 mmol) in anhydrous toluene was heated to reflux with stirring for 6 h. Then the reaction mixture was cooled to room temperature, poured into water, stirred vigorously and extracted thrice with ethyl acetate, dried over anhydrous Na2SO4, concentrated under reduced pressure and purified by flash chromatography to afford compounds 14a-f in 54-68% yields. 6.1.17 4-Methyl-1-(5-vinylpyridin-2-yl)piperazin-2-one (14b) A mixture of 2-bromo-5-vinylpyridine 3b (0.15 g, 0.81 mmol), 4-methylpiperazin-2-one (0.18 g, 1.63 mmol), N,N’-dimethylethylene diamine (0.007 g, 0.08 mmol), K2CO3 (0.22 g, 1.63 mmol) and CuI (0.007 g, 0.04 mmol) in anhydrous toluene was heated to reflux and the reaction was continued as described in general procedure IV to afford 14b (0.11 g) in 62.8% yield. 1H NMR (400 MHz, CDCl3): delta 8.40 (d, J = 2.3 Hz, 1H), 8.12 (dd, J = 8.6, 1.0 Hz, 1H), 7.80 (dd, J = 8.7, 2.4 Hz, 1H), 6.72 (dd, J = 17.7, 11.0 Hz, 1H), 5.81 (dd, J = 17.7, 0.7 Hz, 1H), 5.38 (dd, J = 11.0, 0.8 Hz, 1H), 3.66-3.76 (m, 2H), 3.28 (s, 2H), 2.76-2.82 (m, 2H), 2.41 (s, 3H); LC-MS: 218 (M++1).

34770-60-0, The synthetic route of 34770-60-0 has been constantly updated, and we look forward to future research findings.

Reference：
Article; Rakesh; Bruhn, David; Maddox, Marcus; Lee, Robin B.; Yang, Lei; Lee, Richard E.; Madhura, Dora B.; Trivedi, Ashit; Meibohm, Bernd; Scherman, Michael S.; Gilliland, Janet C.; Gruppo, Veronica; McNeil, Michael R.; Lenaerts, Anne J.; Bioorganic and medicinal chemistry; vol. 20; 20; (2012); p. 6063 – 6072,10;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

55121-99-8,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.

Example 6:2-methyl-N5-(4-(4-methylpiperazine- 1 -carbonyl)phenyl)- 1 -phenyl-6,7-dihydro- 1 H- pyrrolo [3 ,2-c]pyridine-3 , 5 (4H)-dicarboxamideA solution of (4-aminophenyl)(4-methylpiperazin-l-yl)methanone (0.037 g) and triethylamine (0.012 mL) in dichloromethane (1.5 mL) was added over 45 minutes to a -78 C solution of triphosgene (0.017 g) in dichloromethane (1 mL). The reaction was stirred for 45 minutes more at -78 C to obtain a carbamic chloride solution. The compound prepared in Example 5 (0.042 g) was suspended in dichloromethane (1 mL) and treated with triethylamine (0.050 mL). The mixture was vigorously stirred for five minutes and was then added dropwise to the carbamic chloride solution aforementioned at -78 C. The reaction was warmed to room temperature, stirred for 1.5 hours and then diluted with ethyl acetate and water. The layers were separated and the aqueous phase was extracted with ethyl acetate three times. The combined organics were dried over anhydrous magnesium sulfate and concentrated. The residue was purified by column chromatography on silica gel (methanol: dichloromethane: triethylamine = 1 :19: 0.04) to obtain the title compound (0.029 g) having the following physical data. 1H NMR (CDCl3): delta 7.56-7.40 (m, 5H), 7.33 (d, J = 8.5 Hz, 2H), 7.18 (d, J = 6.9 Hz,2H), 7.12 (s, IH), 5.62 (s, 2H), 4.78 (s, 2H), 3.88-3.37 (m, 6H), 2.73-2.56 (m, IH),2.53-2.24 (m, 1 IH);Mass data (ESI, Pos.): m/z 501 (M + H)+.

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

Reference：
Patent; ARRAY BIOPHARMA, INC.; WO2008/134354; (2008); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5317-33-9, 3-(4-Methylpiperazin-1-yl)propan-1-ol is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

5317-33-9, 1.5 324.34 mg of 3-(3-aminobenzyl)-5-methoxy-2-benzoxazolinone are suspended in 5 ml of dichloromethane in a reaction vial fitted with a magnetic stirrer, 252.03 mul of triethylamine are added, 145.35 mg of bis-(trichloromethyl) carbonate (triphosgene) are carefully added with cooling and stirring, and the mixture is stirred at RT for 10 minutes. 208.88 mg of 3-(4-methyl-1-piperazinyl)-1-propanol are then added, and the mixture is stirred at RT for 24 h in a tightly sealed reaction vial in a multiple synthesiser. The reaction mixture is diluted with dichloromethane, washed with water, dried and filtered, and the solvent is removed. The residue is adsorbed onto silica gel and chromatographed over a flash column on a FlashMaster with 20 g of LiChroprep 60 (25-40 mum) and dichloromethane+0-50% of methanol. The residue is dissolved in methanol, ethereal hydrochloric acid is added, the salt is precipitated using ether, and the supernatant solution is poured off. The salt is crystallised using methanol/ether, filtered off with suction, washed with ether and dried; m.p. 120, decomposition from 150;ESI: 455 (M+H); HPLC: Rt=4.00 (method A);yield: 383 mg (61%) of ?A1?.

As the paragraph descriping shows that 5317-33-9 is playing an increasingly important role.

Reference：
Patent; MERCK PATENT GESELLSCHAFT MIT BESCHRANKTER HAFTUNG; US2010/280030; (2010); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

21655-48-1, cis-2,6-Dimethylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Reference Example 38; 2-Chloro-6-(alpha5-3,5-dimethyI-piperazin-l-yImethyl)-4-morphoIin-4-yl-thieno[3,2- d]pyrimidipite; To a solution of 6-bromomethyl-2-chloro-4-morpholin-4-yl-thieno[3,2- djpyrimidine (150 mg, 0.43 mmol) in DMF (4 mL) were added (cz>)-2,6-dimethyl- piperazine (74 mg, 0.648 mmol) and potassium carbonate (117 mg, 0.847 mmol). The resulting mixture was stirred at RT for 17 h, then concentrated in vacuo. The resulting residue was triturated with water to give the title compound as an off-white solid (127 mg, 77 percent). [M + H]+ 382.3, 21655-48-1

21655-48-1 cis-2,6-Dimethylpiperazine 6950261, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; PIRAMED LIMITED; WO2007/122410; (2007); A1;,
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