Heterocyclic Building Blocks-piperazine

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.262368-30-9,N-(4-Aminophenyl)-N-methyl-2-(4-methylpiperazin-1-yl)acetamide,as a common compound, the synthetic route is as follows.

262368-30-9, A 500ml reaction flask was charged 30g of compound V, 22.5g compound of the VI, ethanol 300ml, sodium bicarbonate and 15g, the reaction was heated to reflux for 2 hours, the reaction mixture was added to 600ml of water, there are large amount of solid precipitated, was filtered, the cake washed with 100ml washed once with methanol, a yellow solid 41.9g nintedanib (I) .Yield 92.7%.

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

Reference：
Patent; Hangzhou Simbos Pharm Co., Ltd; Li, Yong; Hu, wei; Du, Huanda; Wang, wanqing; Liu, YanHua; (8 pag.)CN105461609; (2016); 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.548762-66-9,(2S,5R)-tert-Butyl 2,5-dimethylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

To a solution of 4-fluorobenzoic acid (0.98 g, 7 mmol) in DMF (10 mL) were added TEA (1.95 mL, 14.0 mmol), BOP (2.06 g, 4.67 mmol) and tert-butyl (2S,5R)-2,5- dimethylpiperazine-1-carboxylate (1.0 g, 4.67 mmol). The reaction mixture was stirred at room temperature for 4 h. The solvent was removed under reduced pressure and the crude compound was purified by flash chromatography (12 g column silica, eluted with 25-40% ethyl acetate/ Pet ether) to obtain tert-butyl (2S,5R)-4-(4-fluorobenzoyl)-2,5- dimethylpiperazine-1-carboxylate (1.1 g, 70.1 % yield) as an off white solid; LCMS: m/z, 337.2 (M+H); rt 1.95 min. LCMS Method Column Name: AQUITY UPLC BEH C18(3.0 x 50 mm) 1.7 ^m Buffer: 10 mM ammonium acetate Mobile phase A:Buffer acetonitrile (95:5) Mobile phase B: Buffer: acetonitrile (5:95) Method:%B: 0 min-20:2 min -100:2.2 min-100 Flow: 0.7 mL/min

548762-66-9, 548762-66-9 (2S,5R)-tert-Butyl 2,5-dimethylpiperazine-1-carboxylate 11745988, apiperazines compound, is more and more widely used in various fields.

Reference：
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

5747-48-8, 11-(Piperazin-1-yl)dibenzo[b,f][1,4]thiazepine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Example 8 1-piperazinyldibenzo[b,f][1,4]thiazepine A 1 liter round bottom flask equipped with stirring rod, thermo pocket, water condenser was charged with solution of 11-chlorodibenzo[b,f][1,4]thiazepine in toluene [52 gm (0.22 moles)], and the mixture was stirred for 15 min 45-50 C. To the resulting solution was added piperazine 73.0 (0.84 moles) at 45-50 C. The reaction mixture was heated to 70-80 C. The reaction mixture was maintained at 70 C. to 80 C. for 120-180 min. The reaction mixture was analyzed by HPLC (to check for absence of compound of formula III) and was cooled to 20 C. to 25 C. The reaction mixture was added 250 cc DM water and was stirred for 30 min. at 25-30 C. The layers were separated and the organic layer washed with 250 cc DM water. The organic phase was distilled off under vacuum below 70 C. Traces of toluene were removed by adding n-butanol. To the resultant oily mass was added 150 cc n-butanol. The mixture was stirred for 24 hrs and chilled to 0-5 C. The reaction mass was filtered with the filtrate (mother liquor) containing 11-piperazinyldibenzo[b,f][1,4]thiazepine. Purity of 11-piperazinyldibenzo[b,f][1,4]thiazepine in toluene was more than 98.0% (area % by HPLC).

5747-48-8, As the paragraph descriping shows that 5747-48-8 is playing an increasingly important role.

Reference：
Patent; Kansal, Vinod Kumar; Ahmad, Suhail; Lal, Kanhaiya; Patil, Bhatu Tumba; US2008/241949; (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.129799-15-1,Methyl 1-Boc-piperazine-2-carboxylate,as a common compound, the synthetic route is as follows.

Example 111a 1-tert-Butyl 2-Methyl 4-benzylpiperazine-1,2-dicarboxylate 111a To a dry 100 ml one necked round bottom flask equipped with a stirring bar was added 1-tert-butyl 2-methyl piperazine-1,2-dicarboxylate (5 g, 20.5 mmol) under N2 (). Anhydrous acetonitrile (60 mL) was added followed by the additions of BnBr (2.7 mL, 22.5 mmol) and triethylamine (8.5 ml, 61.5 mmol). A condenser was then put on to the flask and the reaction mixture was heated at 71 C. for 45 minutes. The reaction mixture was allowed to come to room temperature and concentrated under reduced pressure. It was then diluted with dichloromethane and washed with water and brine. The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The crude compound was purified with flash column (PE: EA=8:1) to yield 4.5 g (66%) of 111a. MS: [M+H]+: 335, 129799-15-1

The synthetic route of 129799-15-1 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; GENENTECH, INC.; Crawford, James John; Young, Wendy B.; US2013/116245; (2013); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

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, Triethylamine (3.7 mL, 27 mmol, 5.0 eq) is added to a solution of 6-chloronicotinic acid ethyl ester (1.0 g, 5.4 mmol, leq), (Patent; NOVARTIS AG; WO2008/110611; (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.196811-66-2,tert-Butyl 4-carbamothioylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

To a stirred solution of tert-butyl 4-carbamothioylpiperazine-1-carboxylate (synthesized according to Example 5, Step 1, 1.31 g, 5.36 mmol) in isopropanol (15 mL), tert-butyl 3-bromo-2,4-dioxopiperidine-1-carboxylate obtained in the first step (1.3 g, 4.46 mmol) was added at rt. The reaction mixture was stirred overnight at 90 C. It was cooleddown to rt and evaporated under reduced pressure. Water (10 mL) was added and the desired product was extracted with diethyl ether (2 x 30 mL), dried over Na2504 and concentrated, affording the title product. Yield: 74% (1.42 g, yellow solid). LCMS:(Method A) 239.0 (M-Boc+H), Rt. 0.70 mm, 48.39% (Max).

196811-66-2, The synthetic route of 196811-66-2 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; ASCENEURON S. A.; QUATTROPANI, Anna; KULKARNI, Santosh, S.; GIRI, Awadut Gajendra; TORONTO, Dawn, V.; CROWE, David, Malcolm; (150 pag.)WO2017/144637; (2017); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

34770-60-0, 4-Methylpiperazin-2-one is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

EXAMPLE 151 EPO Preparation of 4-(4-methyl-2-piperazinon- 1 -yl)piperidin- 1 -yl-2-(2-methoxyphenyl)-2-(4- chlorophenylaminocarbonylamino)-acetamide; A. Preparation of 4-(4-methyl-2-piperazinon-l-yl)piperidine; [0523] To a solution of 2-pirhoerazinone (200 mg, 2.00 nimol) and HCHO (37% aq., 0.200 mL, 2.69 mmol) in MeOH (6 niL) at room temperature, NaBH3CN (162 mg, 2.57 mmol) was added. After being stirred at room temperature overnight, the solution was concentrated in vacuo. The residue was partitioned between 5% aq. NaHCO3 and nBuOH. The nBuOH phase was separated, concentrated in vacuo to give the 4-methyl-2-piperazinone as a semi-solid (118 mg). MS 115.5 (M+H).[0524] A mixture of 4-iodopyridine (218 mg, 1.06 mmol), 4-methyl-2-piperazinone (106 mg, 0.929 mmol), K3PO4 (425 mg, 2.00 mmol) and 1,2-trans-diaminocyclohexane (0.050 mL, 0.41 mmol) in anhydrous dioxane (3.0 mL) was degassed with Ar before being charged with CuI (40 mg, 0.21 mmol). The mixture in a sealed tube was heated at 1100C overnight. The mixture was purified by a prep-TLC using MeOHZCH2Cl2 (10/90) as solvents to give 1- (pyridin-4-yl)-4-methyl-2-piperazinone (42 mg). MS 192.5 (M+H).[0525] A mixture of l-(pyridin-4-yl)-4-methyl-2-piperazinone (12 mg, 0.063 mmol) and PtO2 (49 mg) in HOAc (6.0 mL) was hydrogenated on a Parr shaker under 40 psi for 3 days. The mixture was filtered through celite. The filtrate was concentrated in vacuo. The residue was dissolved in IN HCl (5.0 mL). The solution was then concentrated in vacuo to give the titled compound as hydrochloride salt (12 mg). MS 198.5 (M+H).

34770-60-0, As the paragraph descriping shows that 34770-60-0 is playing an increasingly important role.

Reference：
Patent; PORTOLA PHARMACEUTICALS, INC.; WO2006/63113; (2006); A2;,
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.13754-38-6,1-Benzoylpiperazine,as a common compound, the synthetic route is as follows.

General procedure: A solution of 2-chloroalkyl/aryl substitutedwith or without N-substitution as well as with or without 5 and/or 6-substituted benzimidazole derivative (1.75g,0.01051mol) and 1-[(4-phenyl)carbonyl]piperazine (3g,0.0105mol) in N, N dimethylformamide was taken in a RBF.K2CO3(2gm,) was added to the reaction mixture. The reaction mixture was stirred for 8h at 80C on a magnetic stirrer (heat + stirring). The progress of the reaction was monitored by thin layer chromatography (TLC).Upon completion of the reaction, water was added to the reaction mixture and the product extracted by shaking the reaction mixture with dichloromethane in a separating funnel.The dichloromethane layer was washed successively with water and brine, dried over anhydrous sodium sulfate. Evaporation of the solvent gave theproduct. 11a-l Recrystallized with various solvent like chloroform, ethanol, methanol.

13754-38-6, 13754-38-6 1-Benzoylpiperazine 762654, apiperazines compound, is more and more widely used in various fields.

Reference：
Article; Kankate, Rani S.; Gide, Parag S.; Belsare, Deepak P.; Oriental Journal of Chemistry; vol. 30; 4; (2014); p. 1855 – 1863;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5308-25-8, 1-Ethylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Into a solution of l-Methyl-4-nitro-2-trifluoromethyl-benzene (1; 15 g, 73 mmol, 1.0 eq.) in carbon tetrachloride (250 ml) are added NBS (13 g, 98 ml, 73 mmol, 1.0 eq.) and AIBN (1.19 g, 7.3 mmol, 0.1 eq.) as an initiator. The reaction is refiuxed overnight and then partitioned with water. The organic layer is separated and the aqueous layer is extracted with dichloromethane. The combined organic extracts are washed with water, dried over EPO Na2SO4, filtered and concentrated to afford the solids. The solids are dissolved in dichloromethane (300 ml). The clear solution is treated with DIEA (12.55 ml, 73 mmol, 1.0 eq.) and N-Ethylpiperazine (8.25 g, 73 mmol, 1.0 eq.). The reaction mixture is stirred at room temperature for 30 minutes (until the completion of reaction as per LCMS). The reaction mixture is washed with water, dried over Na2SO4, filtered and concentrated to afford the crude product. The crude product is purified by flash column chromatography using 1 :1 v/v hexanes: ethyl acetate as solvent to afford title compound 2 as a solid., 5308-25-8

5308-25-8 1-Ethylpiperazine 79196, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; IRM, LLC; WO2006/124462; (2006); A2;,
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

1-(2-Chloroethyl)-4-methylpiperazine (58b) was prepared by refluxing 2-(4- methylpiperazin-1-yl)ethanol (58a) (1.1 g, 7.33 mmol) with thionyl chloride (10 mL). The reaction mixture was cooled to 20 °C, and poured into ice/water. The aqueous solution was then treated with 6-bromo-4-hydroxy-2-methyl-9H-xanthen-9-one (28b) (260 mg, 0.85 mmol), tetrabutylammonium bromide (100 mg), KOH (1.12 g, 20 mmol), and CH2C12 (50mL), and the mixture was stirred for 3 days. The CH2C12 layer was separated, and the aqueous layer was further extracted with CH2C12. The combined CH2C12 extracts were dried (Na2SO4) and the solvent was removed. Chromatography on neutral alumina eluting with 0-20percent hexanes/EtOAc followed by 0-1percent CH2C12/MeOH gave crude material which was re-columned in Si02 eluting with 20percent hexanes/EtOAc to remove impurities, then with0-4percent CH2C12/MeOH to elute 6-bromo-2-methyl-4-(2-(4-methylpiperazin- 1 -yl)ethoxy)-9H- xanthen-9-one (58c): MS (APCI) m/z: 431 and 433 (M+H). This was used directly without further purification., 5464-12-0

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

Reference：
Patent; AUCKLAND UNISERVICES LIMITED; MARSHALL, Andrew James; BUCHANAN, Christina Maree; REWCASTLE, Gordon William; LU, Guo-Liang; FLANAGAN, Jack Urquhart; BONNET, Muriel; SHEPHERD, Peter Robin; JAMIESON, Stephen Michael Frazer; GAMAGE, Swarnalatha Akuratiya; DENNY, William Alexander; (213 pag.)WO2018/83635; (2018); A2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics