Heterocyclic Building Blocks-piperazine

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.30459-17-7,1-(4-Trifluoromethylphenyl)piperazine,as a common compound, the synthetic route is as follows.

Acetic acid (33 ??_, 0.59 mmol), HOBt (87 mg, 0.65 mmol), TBTU (208 mg, 0.65 mmol), anhydrous triethylamine (131 ??_, 0.94 mmol) and anhydrous DMF (2 mL) were placed in an oven-dried Schlenk tube under a nitrogen atmosphere. The resulting solution was stirred at room temperature for 15 minutes. A second Schlenk tube was prepared containing 1-(4-(trifluoromethyl)phenyl)piperazine (150 mg, 0.65 mmol) and anhydrous DMF (1 mL) under a nitrogen atmosphere. The resulting solution was stirred until complete dissolution of the piperazine had occurred. The piperazine solution was then transferred, via a cannula, to the first Schlenk tube containing the carboxylic acid. The resulting solution was stirred under nitrogen and monitored by TLC. After 24 hours, the DMF was removed under reduced pressure and the resulting oil was acidified using a 0.1 M HCI solution. The aqueous mixture was extracted with DCM (20 mL, followed by 4 x 10 mL) and the organic layer washed with a saturated sodium bicarbonate solution (3 x 20 mL) and brine (3 x 20 mL). The organic layer was dried over magnesium sulphate and the solvent removed in vacuo. The residue was purified using flash chromatography (4:1 , EtOAc:n-hexane) to obtain the desired product in a 57% yield. H NMR (300 MHz, CDCI3) ? 7.49 (d, J = 8.7 Hz, 2H), 6.91 (d, J = 8.7 Hz, 2H), 3.79-3.76 (m, 2H), 3.65-3.61 (m, 2H), 3.31-3.24 (m, 4H), 2.14 (s, 3H). 3C NMR (75 MHz, CDCI3) 168.0, 151.9, 125.4 (q, J = 3.75 Hz), 1 19.6 (q, J = 33 Hz), 1 18.2 (q, J = 268.5 Hz), 1 15.0, 48.3, 48.0, 45.8, 41.0, 21.3. MS (+ESI) calcd for C13 H15 F3 N2 O m/z: [M + H]+, 273.1209; found 273.1222 [Diff(ppm) = 4.8].

30459-17-7, As the paragraph descriping shows that 30459-17-7 is playing an increasingly important role.

Reference：
Patent; NATIONAL UNIVERSITY OF IRELAND, MAYNOOTH; STEPHENS, John; FINDLAY, John; KINSELLA, Gemma; MARTIN, Darren; DEVINE, Robert; VELASCO-TORRIJOS, Trinidad; WO2013/60860; (2013); A1;,
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13889-98-0, 1-Acetylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,13889-98-0

INTERMEDIATE 10( S)-ter t-Butyl 1 – |~2-(4-acetylpiperazin- 1 -yl)-7-fluoro-8-methylquinolin-3 – yl 1 ethylcarbamateIntermediate 9 (3.0 g, 0.89 mmol) in NMP (15 mL) was treated with 1 -acetyl – piperazine (2.8 g, 22 mmol) and DIPEA (5.7 g, 44 mmol) and heated in a sealed tube at 140C for 72 h. The reaction mixture was cooled to r.t. and diluted with ethyl acetate/ water. The organic phase was washed (water, brine), dried (phase separation cartridge) and evaporated in vacuo. The resulting residue was purified by silica flashchromatography, eluting with 50-60% EtOAc in isohexane, to give the title compound (3.4 g 89%) as a cream solid. deltaEta (CDC13) 7.95 (1H, s), 7.53 (1H, dd, J 8.9, 6.0 Hz), 7.16 (1H, t, J 8.9 Hz), 5.08-5.02 (1H, m), 3.95-3.90 (1H, m), 3.78-3.73 (2H, m), 3.64 (1H, m), 3.61-3.40 (2H, m), 3.19-3.15 (2H, m), 2.59 (3H, d, J2.4 Hz), 2.17 (3H, s), 1.58 (3H, d, J 6.5 Hz), 1.48-1.42 (9H, m).

As the paragraph descriping shows that 13889-98-0 is playing an increasingly important role.

Reference：
Patent; UCB PHARMA S.A.; BUeRLI, Roland; HAUGHAN, Alan, Findlay; MATTEUCCI, Mizio; OWENS, Andrew, Pate; RAPHY, Gilles; SHARPE, Andrew; WO2011/58110; (2011); A1;,
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Piperazines – an overview | ScienceDirect Topics

928025-56-3, (S)-tert-Butyl 3-ethylpiperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Example 111a (S)-tert-Butyl 3-Ethyl-4-(6-nitropyridin-3-yl)piperazine-1-carboxylate 111a 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, 0.50 mmol), 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 100 C. 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 111a (700 mg, 22%) as a yellow solid. MS: [M+H]+ 336, 928025-56-3

928025-56-3 (S)-tert-Butyl 3-ethylpiperazine-1-carboxylate 24820542, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; GENENTECH, INC.; Crawford, James John; Ortwine, Daniel Fred; Wei, BinQing; Young, Wendy B.; US2013/116246; (2013); 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.192130-34-0,tert-Butyl 4-(2-aminoethyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

A mixture of 2- (5-amino-2- (furan-2-yl) -7H-pyrazolo [4, 3-e] [1, 2, 4] triazolo [1, 5-c] pyrimidin-7-yl) -2-phenylpropanoic acid (60 mg, 0.154 mmol) , the product of Step B (35.3 mg, 0.154 mmol) , HATU (70.6 mg, 0.18 mmol) and DIPEA (40 mg, 0.308 mmol) in DMF (3 mL) was stirred overnight. The reaction mixture was poured into H 2O (15 mL) and extracted with EtOAc (10 mL x 3) . The combined organic layers were washed with brine, dried over Na 2SO 4, concentrated and purified by prep-TLC (petroleum ether/EtOAc=1: 2) to give the target compound (34 mg, 36.8%) as a white solid. MS: M/e 601 (M+1) +., 192130-34-0

As the paragraph descriping shows that 192130-34-0 is playing an increasingly important role.

Reference：
Patent; BEIGENE, LTD.; ZHANG, Guoliang; ZHOU, Changyou; (152 pag.)WO2019/196803; (2019); 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.1152367-80-0,(S)-1,3-Dimethylpiperazine,as a common compound, the synthetic route is as follows.

Intermediate 11CSV 2,4-dimethylpiperazi – 1 -carbonyl chlorideTo a solution of triphosgene (1.04 g, 3.5 mmol) in DCM (20 mL) under nitrogen was added pyridine (2.3 g, 28.0 mmol) drop-wise at 0C followed by addition of (S)-l,3- dimethylpiperazine (800 mg, 7.0 mmol) in DCM (30 mL), the reaction mixture was warmed to RT and stirred overnight as monitored by TLC (Rf= 0.9, PE: EtOAc = 1 : 1). The mixture was concentrated to give Intermediate 1 1 (3 g, crude) which was used without purification.

1152367-80-0, As the paragraph descriping shows that 1152367-80-0 is playing an increasingly important role.

Reference：
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; LI, David, Yunzhi; WANG, Jiabing; YANG, Zhenfan; ZENG, Qingbei; ZHANG, Xiaolin; WO2014/135876; (2014); 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

In a sealed tube, 2-(2,8-dimethylimidazo[l,2-b]pyridazin-6-yl)-7-fluoro-pyrido[l,2- a]pyrimidin-4-one (Intermediate 2; 50 mg, 0.162 mmol), and cis-2,6-dimethylpiperazine (74 mg, 0.647 mmol, 4.0 eq.) were stirred in DMSO (1.5 mL) at 110C overnight. The solvent was removed under high vacuum. The residue was taken up in CH2CI2and washed with an aqueous saturated solution of NaHC03. The organic layer was separated and dried over Na2S04and concentrated in vacuo. The crude was purified by column chromatography (S1O2,CH2Cl2/MeOH=95/5 to 90/10) to afford the title product (32 mg, 49%) as a light yellow solid. MS m/z 404.4 [M+H+]., 21655-48-1

As the paragraph descriping shows that 21655-48-1 is playing an increasingly important role.

Reference：
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; MCCARTHY, Kathleen Dorothy; METZGER, Friedrich; RATNI, Hasane; (76 pag.)WO2017/81111; (2017); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

196811-66-2, tert-Butyl 4-carbamothioylpiperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

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 cooled down 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 Na2SO4 and concentrated, affording the title product. Yield: 74% (1.42 g, yellow solid). LCMS: (Method A) 239.0 (M-Boc+H), Rt. 0.70 min, 48.39% (Max)., 196811-66-2

As the paragraph descriping shows that 196811-66-2 is playing an increasingly important role.

Reference：
Patent; ASCENEURON SA; QUATTROPANI, Anna; KULKARNI, Santosh S.; GIRI, Awadut Gajendra; (243 pag.)WO2016/30443; (2016); 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.21655-48-1,cis-2,6-Dimethylpiperazine,as a common compound, the synthetic route is as follows.

Adding 2, 6-lupetazin (11.4g, 100mmol, 1eq) and di-tert-butyl dicarbonate (21.8g, 100mmol, 1eq) into a 250mlflask; and then adding 100ml tetrahydrofuran, reacting under room temperature for 4 hours; and condensing up tetrahydrofuran(i.e., condensing tetrahydrofuran until used up), 21.4g orange-colored oily substance ZTH-1 is obtained, whereinthe yield is 100%., 21655-48-1

As the paragraph descriping shows that 21655-48-1 is playing an increasingly important role.

Reference：
Patent; Suzhou Maidixian Pharmaceutical Inc.; Zhang, Nan; Zhong, Rong; ZHANG, Nan; ZHONG, Rong; EP2589601; (2013); 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.59878-57-8,1-(Cyclopropylcarbonyl)piperazine,as a common compound, the synthetic route is as follows.

59878-57-8, 0.62g to 1.0g of Intermediate VI and cyclopropylmethyl – piperazin-1-yl – methyl ketone was added to a 100mL one-neck flask was added10mLDMF clear solution was stirred, then add 2.05gHBTU, 0.82g triethylamine, room temperature for 5h. After completion of the reaction the reactionIt was poured into water, extracted with ethyl acetate, dried over anhydrous sodium sulfate spin column chromatography to give 1.1g solid.

59878-57-8 1-(Cyclopropylcarbonyl)piperazine 2064235, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; Warwick Nanjing Pharmaceutical Technology Co., Ltd.; Zhang, Xiaoqing; Song, Zhinchun; Bao, Jinyuan; Jiang, Yuwei; (25 pag.)CN105254628; (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.59702-07-7,1-Methylpiperazin-2-one,as a common compound, the synthetic route is as follows.

A mixture of N [5-chloro-7- (3-isopropoxyprop-1-yn-1-yl)-1, 3-benzodioxol-4-yl]-7- (3- chloropropoxy) -6-methoxyquinazolin-4-amine (0.22g, 0. 43mmol), triethylamine (0. 29ml, 2.13mmol), 1-methylpiperazin-2-one (0.24g, 2. 13mmol) in 2-methoxyethanol (3ml) was heated to 80 C for 12 hours and then at 100 C for 7 hours. The solvent was removed under reduced pressure and the residue was partitioned between dichloromethane and water. The organic layer was separated, dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by flash chromatography on silica eluting with a mixture of 2-8 percent methanol in dichloromethane to give the product as an light orange solid (0.129g, 51percent). NMR Spectrum: (DMSOd6) 1. 18 (d, 6H), 1.98 (m, 2H), 2.52 (t, 2H under DMSO), 2.72 (t, 2H), 2.88 (s, 3H), 3.04 (s, 2H), 3.34 (t, 2H under H20), 3.83 (m, 1H), 3.97 (s, 3H), 4.22 (t, 2H), 4.42 (s, 2H), 6.17 (s, 2H), 7.15 (s, 1H), 7.21 (s, 1H), 7.83 (s, 1H), 8.34 (s, 1H), 9.52 (s, 1H). Mass Spectrum: M+H+ 596 and M+ll 594

59702-07-7, As the paragraph descriping shows that 59702-07-7 is playing an increasingly important role.

Reference：
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2004/4732; (2004); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics