Heterocyclic Building Blocks-piperazine

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.108-49-6,2,6-Dimethylpiperazine,as a common compound, the synthetic route is as follows.

Step 1 Synthesis of 3,5-Dimethyl-piperazine-1-carboxylic acid tert-butyl ester A solution of BOC-anhydride (374 mg, 1.71 mmol) in chloroform (2 mL) was added dropwise to a stirred solution of 2,5-dimethyl-piperazine (20 g, 266.5 mmol) in chloroform (2 mL) and the resulting mixture was stirred at room temperature for 4 hr. The reaction mixture was then diluted with cold water and extracted with chloroform, dried the organic layer over sodium sulfate and concentrated under reduced pressure to afford 331 mg (88.6percent yield) of 3,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester. LCMS Purity: 91.3percent., 108-49-6

The synthetic route of 108-49-6 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Bischoff, Alexander; Subramanya, Hosahalli; Sundaresan, Kumar; Sammeta, Srinivasa Raju; Vaka, Anil Kumar; US2010/160323; (2010); A1;,
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55112-42-0, 4-Methyl-1-piperazinecarbonyl Chloride Hydrochloride is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,55112-42-0

4-Methyl-l-piperazinecarbonyl chloride hydrochloride (19.9 mg, 0.1 mmol) was added to a solution of 16 (20 mg, 0.05 mmol) and anhydrous pyridine (25 muml, 0.3 mmol) in 3% allyl alcohol in dry methylene chloride (4 ml) and the mixture was stirred for 16 h. Purification of the crude product on silica gel yielded 17 (23.6 mg, 91%). 1NMRDMSOd6) delta 12.03 (s, IH), 8.41 (s, IH), 8.21 (s, IH), 8.01 (d, IH, J=8.4 Hz), 7.88 (d, IH, J=8.4 Hz), 7.82 (dd, IH, J=8.4 Hz), 7.58 (t, IH, J=8.1 Hz), 7.51 (d, IH, J=8.4 Hz)5 7.46 (t, IH, J=7.6 Hz), 7.37 (s, IH), 4.86 (t, IH, J=10.8 Hz), 4.57 (dd, IH, J=10.8 Hz), 4.38 (in, IH), 4.06 (dd, IH, J=I 0.8 Hz), 3.86 (dd, IH, J=I 1 Hz), 3.41 (br, 4H), 3.29 (br, 4H), 2.82 (s, 3H), 2.57 (s, 3H).

55112-42-0 4-Methyl-1-piperazinecarbonyl Chloride Hydrochloride 3016934, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; MEDAREX, INC.; WO2007/51081; (2007); A1;,
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Piperazines – an overview | ScienceDirect Topics

170911-92-9, tert-Butyl 4-(4-aminophenyl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

p-Nitrophenyl chloroformate (4.16 g) and pyridine (2.0 mL) were added to a solution of N-tert-butyloxycarbonyl-N’-(4-aminophenyl)-piperazine (5.54 g) in anhydrous tetrahydrofuran (40 mL) at 0C. The reaction mixture was stirred at 0C for one hour and stirred at room temperature for three hours and diluted with 1N hydrochloric acid, followed by extraction with ethyl acetate. The organic layer was washed with a saturated sodium hydrogen carbonate aqueous solution and saturated brine, dried over sodium sulfate and concentrated. The obtained solid was collected by filtration and dried and 6.42 g (72%) of the title compound was obtained as a pale yellow solid. 1H NMR(400MHz,DMSO-d6):delta(ppm)=8.26(2H, d, J=9.OHz), 7.37(2H, d, J=9.0Hz), 7.34(2H, d, J=9.OHz), 6.97(IH, brs), 6.92(2H, d, J=9.OHz), 3.58(4H, t, J=5.1Hz), 3.10(4H, t, J=5.1Hz), 1.48(9H, s).

170911-92-9, The synthetic route of 170911-92-9 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Sankyo Company, Limited; EP1764360; (2007); A1;,
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259808-67-8, 1-Boc-3,3-Dimethylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To a solution of 27 (1.00 g, 4.6 mmol) in CH2C12 (10 mL) at0C was charged with Et3N (2.30 g, 23 mmol) followed by MsC1 (0.59 mg, 7.0 mmol). The reaction mixture was stirred at room temperature for 2 h. Water (50 mL) was added to the reaction mixture and extracted with CH2C12 (2 x 50 mL). The organic phase was separated, dried over anhydrous Na2504, filtered and concentrated to afford 28 [1.20 g (cmde)j as a solid, whichwas used for the next step without further purification.

259808-67-8, 259808-67-8 1-Boc-3,3-Dimethylpiperazine 22710387, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; IOMET PHARMA LTD.; MERCK SHARP & DOHME CORP.; COWLEY, Phillip, M.; WISE, Alan; BROWN, Thomas, J.; MCGOWAN, Meredeth, A.; ZHOU, Hua; HAN, Yongxin; (223 pag.)WO2017/7700; (2017); A1;,
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Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.5747-48-8,11-(Piperazin-1-yl)dibenzo[b,f][1,4]thiazepine,as a common compound, the synthetic route is as follows.

Compound 12(20.00 gm, 67.71 mmol), Boc protected Phenyl alanine (19.75 gm, 74.46 mmol),TBTU (32.61 gm, 101.57 mmol), DMF (200 mL, 10 Vol) and DIPEA (26.25 gm, 203.13mmol) were taken in a round bottom flask at room temperature under nitrogenatmosphere. The reaction was stirred for 12 hours at the same temperature and then monitored by TLC. After completion of thestarting material the reaction mixture was diluted with water (600 mL) andstirred for 1 hour at room temperature. The solids were filtered and washedwith water (100 mL x 2) and then dried under vacuum at 50 C to yield 30 gof Compound13 (Yield 82%) as an off-white solid. Offwhite solid; m.p. 120-124 C; 1H NMR (400 MHz, DMSO-d6): delta 7.54-7.56(d, 1H, J=8.0 Hz), 7.42-7.47 (m,4Hz), 7.17-7.25 (m, 7H), 6.98-7.00 (d, 1H, J=8.0Hz), 6.88-6.92 (1H, t, J=7.6 Hz),4.58-4.60 (d, 1H, J=7.2 Hz),3.44-3.82 (m, 6H), 3.11-3.19 (bs, 1H), 2.75-2.90 (m, 3H) and 1.30 (s, 9H); Massm/z = 543 (M+H)+., 5747-48-8

Big data shows that 5747-48-8 is playing an increasingly important role.

Reference：
Article; Gudisela, Mura Reddy; Srinivasu; Mulakayala, Chaitanya; Bommu, Praveen; Rao, M.V. Basaveswara; Mulakayala, Naveen; Bioorganic and Medicinal Chemistry Letters; vol. 27; 17; (2017); p. 4140 – 4145;,
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With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.120737-59-9,tert-Butyl 3-methylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

General Procedure: To a 75 mL screw-cap round bottom flask equipped with a stir bar were added l-bromo-2,4-dichlorobenzene (0.72 mL, 5.99 mmol), 3-methyl-piperazine-l-carboxylic acid tert-butyl ester (1.0 g, 4.99 mmol), 2-di-tert-butylphosphino-2′-(N,N- dimethylamine)biphenyl (51.1 mg, 0.15 mmol), tris(dibenzylideneacetone)dipalladium (45.7 rag, 0.05 mmol) and tetrahydrofuran (30 mL). The reaction flask was flushed with nitrogen for 5 minutes and then lithium bis(trimethylsilyl)amide (1 M in tetrahydrofuran, 6.99 mL, 6.99 mmol) was added in one portion. The reaction flask was sealed and the reaction mixture was stirred at room temperature for 72 hours. The reaction mixture was concentrated in vacuo and the residue purified on silica gel using hexanes: acetone = 98:2 to give the desired product as an off-white solid (130 mg, 8 percent). 1H NMR (300 MHz, CDCl3): delta 6.77 (t, IH)5 6.68 (d, 2H)5 4.10 (bs, IH), 3.85 (bss 2H), 3.12 (m, 4H). 1.48 (s, 9H), 1.04 (d, 3H).

120737-59-9, The synthetic route of 120737-59-9 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; ASTRAZENECA AB; NPS PHARMACEUTICALS, INC.; WO2007/87135; (2007); A2;,
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

General procedure: To a stirred solution of 3 (4, 5) (0.10 mmol) in DMSO (10 ml) were added ZH (0.12 mmol) and K2CO3 (27.6 mg 0.20 mmol). After stirring at 80 C for 8 hours, the mixture was cooled to room temperature and poured into water, the precipitation was filtered and dried directly for next step. To a solution of above solid (0.10 mmol) in dry THF (10 ml) was added LiAlH4 (11.4 mg, 0.30 mmol) at 0 C. After stirring at room temperature for 4 h, the mixture was quenched with water and extracted by CH2Cl2 (10 ml). The extraction was dried over anhydrous MgSO4 and filtered. The filtration was concentrated for next step. To a solution of above crude solid (0.12 mmol) in dry CH2Cl2 (10 ml) were added compound 6 (7-11) (0.10 mmol), TEA (22.2mg, 0.22 mmol) and BopCl (30.4 mg, 0.12 mmol). After stirring at room temperature for 12 h, the mixture was washed with brine and dried over anhydrous MgSO4, filtered and concentrated. The residue was purified by silica gel column (CH2Cl2 : MeOH = 100 : 1) to yield compounds 1, 2, A, B, C., 115761-79-0

115761-79-0 1-(2,4-Difluorophenyl)piperazine 2734637, apiperazines compound, is more and more widely used in various fields.

Reference：
Article; Wang, Hongjian; Lv, Kai; Li, Xiaoning; Wang, Bo; Wang, Apeng; Tao, Zeyu; Geng, Yunhe; Wang, Bin; Huang, Menghao; Liu, Mingliang; Guo, Huiyuan; Lu, Yu; Chinese Chemical Letters; vol. 30; 2; (2019); p. 413 – 416;,
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.163765-44-4,(R)-1-Boc-3-Methylpiperazine,as a common compound, the synthetic route is as follows.

To a stirred solution of tert-butyl (3R)-3-methylpiperazine-1-carboxylate (500 mg, 2.5mmol), 6-chloropyridine-3-carbonitrile (415 mg, 3 mmol) in DMSO (10 mL), potassiumcarbonate (690 mg, 5 mmol), Cu (MeCN)4PF6(18 mg, 0.05 mmol) were added at RT. Thereaction mixture was heated at 140 C for 4 h (TLC indicated complete consumption of thestarting materials), brought toRT, diluted with water (30 mL) and extracted with EtOAc (3 x40 mL). The combined organic extracts were washed with water (30 mL), brine (40 mL),dried over Na2S04 and concentrated under reduced pressure to afford the crude compound.The crude material was purified by column chromatography (100-200 mesh silica gel, 7 g,30% EtOAc-hexane) to afford tert-butyl (3R)-4-(5-cyano-2-pyridyl)-3-methyl-piperazine-1-carboxylate (415 mg, 55%) as an off-white solid.1H NMR [300 MHz, CDCh]: J 8.39 (d, J = 2.4 Hz, 1H), 7.62-7.58 (m, 1H), 6.54 (d, J = 9.0Hz, 1H), 4.51 (brs, 1H), 4.13-3.89 (m, 3H), 3.27-3.13 (m, 2H), 3.00 (brs, 1H), 1.45 (s, 9H),1.23-1.16 (m, 3H).LCMS: m/z: 247.46 [M-tBu] +., 163765-44-4

163765-44-4 (R)-1-Boc-3-Methylpiperazine 2756811, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; MITOBRIDGE, INC.; TAKAHASHI, Taisuke; KLUGE, Arthur; LAGU, Bharat; JI, Nan; (162 pag.)WO2018/125961; (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.67455-41-8,4-(Piperazin-1-yl)aniline,as a common compound, the synthetic route is as follows.

Amine (2.5 mmol) was added to the mixture of bis-chloride (1) (0.419 g, 1 mmol) in10 mL of dry pyridine and the whole was mixed at 70 C for 12 h. The mixture was cooled down toroom temperature and the formed precipitate was filtered off and washed with ether. The raw productwas purified through recrystallization from ethanol., 67455-41-8

The synthetic route of 67455-41-8 has been constantly updated, and we look forward to future research findings.

Reference：
Article; Zieba, Andrzej; Latocha, Ma?gorzata; Sochanik, Aleksander; Nycz, Anna; Ku?mierz, Dariusz; Molecules; vol. 21; 11; (2016);,
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.

Racemic 2-piperazinecarboxylic acid dihydrochloride (1) (0.78 g,6 mmol) was dissolved in aqueous sodium hydroxide (0.96 g,40 mmol) solution. Then a solution of di-tert-butyl dicarbonate (3.9 g, 17.9 mmol) in dioxane (25 mL) was added slowly. The reaction mixture was stirred overnight at room temperature. Subsequently,1 M hydrochloric acid was added to the reaction system to adjust the pH of the reaction solution to about 4. It was extracted with ethyl acetate (3 20 mL), and the organic phase was combined and dried over anhydrous sodium sulfate. The mixture was concentrated under vacuum to afford 0.88 g (2.67 mmol, 45% yield) 2 as a white solid and used directly in the next reaction. 1H NMR (500 MHz, DMSO-d6) delta 12.73 (s, 1H), 4.43 (m, 1H), 4.32 (m, 1H), 3.83(m, 1H), 3.66 (m, 1H), 3.05 (m, 2H), 2.78 (m, 1H), 1.38 (s, 18H). 13C NMR (126 MHz, DMSO-d6) delta 171.71, 171.53, 154.91, 154.68, 79.63,79.45, 79.18, 54.39, 53.07, 27.87. ESI-HRMS Calculated forC15H27N2O6 [M+H]+: 331.1869, Found: 331.1872., 3022-15-9

3022-15-9 Piperazine-2-carboxylic acid dihydrochloride 2723757, apiperazines compound, is more and more widely used in various fields.

Reference：
Article; Chen, Hongli; Huang, Rong; Jiang, Biao; Sheng, Yao; Wei, Ding; Yu, Jianghui; European Journal of Medicinal Chemistry; vol. 190; (2020);,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics