Heterocyclic Building Blocks-piperazine

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, 2.0 g, 8.16 mmol) in dioxane (20 mL), TEA (1.7 mL, 10.6 mmol) and 1-bromobutan-2-one (1.2 mL, 10 mmol) were added and stirred at 80 C for 16 h. The completion of the reaction was monitored by TLC. The reaction mixture was quenched with water (10 mL) and extracted with EtOAc (2 x 25 mL). The organic layer was separated, dried over anhydrous Na2SO4, concentrated under vacuum. The resulting product was taken as such for next step. Yield: 86% (2.1 g, pale yellow solid). LCMS: (Method A) 298.0 (M+H), Rt. 2.94 min, 93.1 % (Max)., 196811-66-2

196811-66-2 tert-Butyl 4-carbamothioylpiperazine-1-carboxylate 12093220, apiperazines compound, is more and more widely used in various fields.

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.3022-15-9,Piperazine-2-carboxylic acid dihydrochloride,as a common compound, the synthetic route is as follows.

To an aqueous (100 ml) sodium hydroxide (4.0 g, 100 mmol) solution of piperazine-2-carboxylic acid dihydrochloride (5 g, 24.63 mmol) is added a solution of di-tert-butyl dicarbonate (11.0 g, 50.45 mmol) in dioxan (50 ml) at 0 C. over a period of half an hour. The reaction mixture is stirred at 0 C. for 1 hr. followed by stirring at room temperature (25 C.) for another 2 hrs. Neutralized (pH 6-7) with aqueous 2N HCl, extracted with ethyl acetate. Organic layer washed with brine solution, dried (Na2SO4) and evaporated in vacuo to yield an oil which solidifies on cooling. (Yield 8.02 g, 98.76%)., 3022-15-9

As the paragraph descriping shows that 3022-15-9 is playing an increasingly important role.

Reference：
Patent; TORRENT PHARMACEUTICALS LTD.; US2003/225102; (2003); A1;,
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

5308-25-8, The inside of a 200 mL flask was placed under a nitrogen atmosphere, and 33.5 mL of toluene and 5.91 g (51.77 mmol) of 1-ethylpiperazine were added and stirred. After cooling to 10 C, 5.00 g (17.26 mmol) of 2-chloro-4- (4-fluorophenyl) -5,6,7,8,9,10-hexahydrocyclo octa [b] pyridine and 1.99 g (20.71 mmol) of sodium-tert-butoxide were added. After reducing the pressure at 100 hPa or less and stirring for 2 minutes, the operation of restoring pressure with nitrogen was repeated 5 times. After adding 0.0775 g (0.345 mmol) of palladium (II) acetate and 0.2715 g (1.035 mmol) of triphenylphosphine, the mixture was depressurized at 100 hPa or less, stirred for 2 minutes, and then pressure restoration with nitrogen was performed three times, and the mixture was stirred under 70 C for 7 hours. The reaction solution was cooled to room temperature, 50 mL of water was added little by little, and after stirring for 30 minutes, the precipitate was removed by filtration using phi 40 mm Kiriyama funnel mounted with 2.50 g of Celite, and washed twice with 10 mL of toluene . The obtained filtrate was transferred to a 300 mL separatory funnel and the aqueous layer was removed (pH 13.0). Water (50 mL) was added to the organic layer, shaken vigorously for 2 minutes, allowed to stand for 10 minutes, and the aqueous layer was removed. This washing operation was repeated until the aqueous layer pH was 9 or less, to obtain a blonanserine toluene solution (49.86 g). Blonanserin content: 5.67 g, reaction yield: 89.12%, HPLC purity: 87.70%.

As the paragraph descriping shows that 5308-25-8 is playing an increasingly important role.

Reference：
Patent; DAI NIPPON PRINTING COMPANY LIMITED; YONEYAMA, TAKUYA; ONOZAWA, TAKASHI; (10 pag.)JP2018/127406; (2018); 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.4318-42-7,1-Isopropylpiperazine,as a common compound, the synthetic route is as follows.

A mixture of l-(4-methoxybenzyl)-7-(3-oxoazetidin-l-yl)-l,5-naphthyridin-2(lH)-one (C-7) (5.796 g, 17.3 mmol, 1.0 eq) and 1-isopropylpiperazine (4.432 g, 34.6 mmol, 2.0 eq) in DCM (150 mL) and acetic acid (0.5 mL) was heated at reflux temperature for 3 h, then NaBH(OAc)3 (7.33 g, 34.6 mmol, 2.0 eq) was added in portions and the resulting mixture was kept reflux overnight. The reactant mixture was cooled and diluted with H20 (300 mL) and extracted with DCM (4 x 100 mL). The combined organic layers were washed with brine, dried over Na2S04 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (2-5percent MeOH-DCM) to afford the desired product l-(4-methoxybenzyl)-7-(3-(4-isopropylpiperazin-l- yl)azetidin-l-yl)-l,5-naphthyridin-2(lH)-one (C-8) (5.6 g, 72.3percent yield ) as a pale solid. :H NMR (300 MHz, CDCl3-<3/4) delta: 7.83 (d, J = 7.5 Hz, 1H), 7.78 (s, 1H), 7.15 (d, J = 6.9 Hz, 2H), 6.85 (d, J = 6.6 Hz, 2H), 6.72 (d, J = 7.2 Hz, 1H), 6.37 (s, 1H), 5.40 (s, 2H), 4.02 (m, 2H), 3.78 (m, 5H), 3.67 (m, 1H), 3.51 (m, 1H), 3.42 (m, 1H), 2.97 (m,lH), 2.80 (m, 4H), 2.55 (m, 2H), 1.17 (d, J= 4.8 Hz, 6H); ESI-MS m/z : 448.3 [M+H]+. 4318-42-7, 4318-42-7 1-Isopropylpiperazine 78013, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; INTELLIKINE, INC.; REN, Pingda; LIU, Yi; LI, Liansheng; CHAN, Katrina; WILSON, Troy, Edward; CAMPBELL, Simon, Fraser; WO2011/149937; (2011); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

314741-40-7, (S)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,314741-40-7

6-(Bromoacetyl)-3 ,4-dihydro- H- isochromen-l-one (-1.54 g, -5.72 mmol, presence of a-chloroketone was noted, -10%) and commercially available (5)-4-N-BOC-2-hydroxymethylpiperazine (1.24 g, 5.72 mmol) were added to a round bottom flask and diluted with THF (50 mL). Diisopropylethylamine (1.30 mL, 7.44 mmol) was then introduced and the mixture left stirring for 14 h at RT during which time a considerable amount of solid had formed (presumably HBr salt of DIPEA). The reaction mixture was diluted with EtOAc, then washed with saturated NH4Claq followed by H20. Both aqueous layers were sequentially back extracted once with another portion of EtOAc, the organics were then combined, dried with MgS04, filtered, and concentrated in vacuo. The recovered crude product was subjected to purification by flash chromatography (Biotage, 50%> EtO Ac/Hex) to afford the title compound.

As the paragraph descriping shows that 314741-40-7 is playing an increasingly important role.

Reference：
Patent; MERCK SHARP & DOHME CORP.; PIO, Barbara; PASTERNAK, Alexander; SHAHRIPOUR, Aurash; TANG, Haifeng; WALSH, Shawn; WO2013/90271; (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.31166-44-6,1-Cbz-Piperazine,as a common compound, the synthetic route is as follows.

To a solution of tert-butyl 2,4-dichloro-8- oxo-5,8-dihydropyrido[3,4-d]pyrimidine-7(6H)-carboxylate (0.400 g, 1.26 mmol) in CH2C12 (5.0 mL) was added N,N-Diisopropylethylamine (0.325 g, 2.51 mmol) followed by benzyl 1- piperazinecarboxylate (0.255 mL, 1.32 mmol) and the reaction stirred at ambient temperature for 1.5 h. The reaction mixture was diluted with CH2CI2 (10 mL) and washed with a 0.5M KHSO4 solution (5 mL), followed by a saturated aqueous NaHCCb solution and brine. The organic layer was dried over Na2S04, filtered and concentrated. The crude product was sonicated in 10 mL MTBE and the resulting solid was isolated by vacuum filtration. The solid was dried in vacuo to provide 0.507 g (80%) of the desired product as an off-white solid which was used directly in the next step. ES+APCI MS m/z 502.1 [M+H]+., 31166-44-6

As the paragraph descriping shows that 31166-44-6 is playing an increasingly important role.

Reference：
Patent; MIRATI THERAPEUTICS, INC.; ARRAY BIOPHARMA, INC.; FISCHER, John, P.; FELL, Jay, Bradford; BLAKE, James, F.; HINKLIN, Ronald, Jay; MEJIA, Macedonio, J.; HICKEN, Erik, James; CHICARELLI, Mark, Joseph; GAUDINO, John, J.; VIGERS, Guy, P.A.; BURGESS, Laurence, E.; MARX, Matthew, Arnold; CHRISTENSEN, James, Gail; LEE, Matthew, Randolf; SAVECHENKOV, Pavel; ZECCA, Henry, J.; (529 pag.)WO2017/201161; (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.169447-70-5,(S)-tert-Butyl 2-methylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

To a microwave tube is added 2-bromobiphenyl (1.0 g, 4.16 mmol), (S)-N- l-t-Boc-2- methylpiperazine (868 mg, 4.16 mmol), 2-dicyclohexylphosphino-2′,4′,6′- triisopropylbiphenyl (X-Phos) (198 mg, 0.416 mmol), Pd2(dba)3 (381 mg, 0.461 mmol), sodium tert-butoxide (400 mg, 4.16 mmol) and toluene (5 mL). The mixture is microwaved at 80 C for 60 min. The reaction is filtered through paper to remove solids, diluted with EtOAc (200 mL), and washed with water (200 mL) then brine (50 mL). The combined organics are dried (Na2SO4) and concentrated in vacuo at 45 0C to give the desired ?-Boc-piperazine intermediate as a crude brown gum. This is reacted without further purification., 169447-70-5

As the paragraph descriping shows that 169447-70-5 is playing an increasingly important role.

Reference：
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; KOWALSKI, Jennifer A.; MARSHALL, Daniel Richard; PROKOPOWICZ, Anthony S. III; SCHLYER, Sabine; SIBLEY, Robert; SORCEK, Ronald John; WU, Di; WU, Frank; YOUNG, Erick Richard Roush; WO2010/126811; (2010); 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.122833-04-9,2-Methoxy-4-(4-methylpiperazin-1-yl)aniline,as a common compound, the synthetic route is as follows.

4.1.4.12 (S)-1-(2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)pyridin-4-yl)-N-(4-(trifluoromethoxy)benzyl)piperidine-3-carboxamide (2d) Compound 5d (257?mg, 0.56?mmol) was reacted with 2-methoxy-4-(4-methylpiperazin-1-yl)aniline (137?mg, 0.62?mmol) according to the general procedure B to give compound 2d (177?mg, yield: 53%).

122833-04-9, As the paragraph descriping shows that 122833-04-9 is playing an increasingly important role.

Reference：
Article; Liu, Siming; Jiang, Ying; Yan, Ruohong; Li, Zhonghuang; Wan, Shanhe; Zhang, Tingting; Wu, Xiaoyun; Hou, Ju; Zhu, Zhengguang; Tian, Yuanxin; Zhang, Jiajie; European Journal of Medicinal Chemistry; vol. 179; (2019); p. 358 – 375;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

115761-79-0, 1-(2,4-Difluorophenyl)piperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,115761-79-0

General procedure: To a solution of methyl hydrazinecarbodithioate 1 (0.34 g, 3 mmol) in ethanol (5 mL) was added the appropriate 1-substituted piperazine 2a-m (6 mmol), and the reaction mixture was stirred at reflux until the evolution of methyl mercaptan almost ceased (it took 5-10 h, and methyl mercaptan was detected by the moistened Pb(OAc)2 paper placed at the upper end of the reflux condenser). After cooling to room temperature, the precipitate was collected by filtration, dried in air. The crude product was purified by recrystallization from the appropriate solvent to give compounds 3a-m.

The synthetic route of 115761-79-0 has been constantly updated, and we look forward to future research findings.

Reference：
Article; Lin, Hui-Hui; Wu, Wei-Yao; Cao, Sheng-Li; Liao, Ji; Ma, Li; Gao, Man; Li, Zhong-Feng; Xu, Xingzhi; Bioorganic and Medicinal Chemistry Letters; vol. 23; 11; (2013); p. 3304 – 3307;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

859518-35-7, tert-Butyl 3-cyanopiperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

859518-35-7, A solution of tert-butyl 3-cyanopiperazine-1-carboxylate, prepared as described in the previous step, (10 g, 0.047 mol) and 2-(2-hydroxyethoxy)acetaldehyde (14.8 g) (see: Bodin, A.,Contact Dermatitis, 2001,44:207) in dichloromethane was treated with formic acid (12.7 g), and the reaction mixture was stirred at room temperature overnight. Sodium cyanoborohydride (7.2 g, 0.118mol) was added in portions. The reaction mixture was stirred at room temperature for 3 hours followed by the addition of water and extraction with dichloromethane. The organic layer was w·ashed with brine, dried over sodium sulfate, filtered, and concentrated. The crude product was purified by column chromatography to provide the product. 1H NMR: (CDCl3, 400 MHz): delta (ppm) 4.15 (s, 1H), 3.69-3.63 (m, 4H), 3.58 (d, J=4.4 Hz, 2H), 3.47-3.44 (m, 4H), 2.61 (d, J=5.2 Hz, 2H), 2.51-2.48 (m, 4H), 1.43 (s, 9H).

As the paragraph descriping shows that 859518-35-7 is playing an increasingly important role.

Reference：
Patent; JANSSEN PHARMACEUTICA NV; ORTHO-CLINICAL DIAGNOSTICS, INC; DONAHUE, Matthew Garrett; GONG, Yong; SALTER, Rhys; HRYHORENKO, Eric; DECORY, Thomas R.; REMMERIE, Bart M.; SANKARAN, Banumathi; WO2014/31600; (2014); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics