Heterocyclic Building Blocks-piperazine

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

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

Reference：
Article; Kankate, Rani S.; Gide, Parag S.; Belsare, Deepak P.; Oriental Journal of Chemistry; vol. 30; 4; (2014); p. 1855 – 1863;,
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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.

The (R) – 1-BOC-3-methyl-piperazine (300 mg, 1 . 5mmol) dissolved in acetonitrile (10 ml) in, adding DIEA (390 mg, 3mmol) and cyclopropyl methyl bromide (235 mg, 1 . 73mmol), 40 C reaction 2d, cessation of the reaction, the reaction liquid concentrated, column chromatography (DCM: the MeOH=40 […] 1) obtaining white semi-solid 320 mg, yield 84.2%., 163765-44-4

The synthetic route of 163765-44-4 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Institute Of Materia Medica Chinese Academy Of Medical Sciences; Xu, Bailing; Chen, Xiaoguang; Yao, Haiping; Ji, Ming; Jin, Jing; Zhou, Jie; Wang, Ke; Zhao, Dalong; (55 pag.)CN105461697; (2016); A;,
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109-07-9, 2-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Example 8 In a 100 ml four-neck flask, 5.04 g (= 0.0503 mole) of racemic 2-methylpiperazine was placed, and 5.37 g of water and 45.13 g of 1-butanol were added for dissolution (water content 10.6 wt%). Furthermore, 3.99 g (= 0.0504 mole) of pyridine was added, being followed by stirring and subsequent cooling down to 0C, and 8.67 g of benzyl chlorocarbonate (= 0.0494 mole, purity by HPLC determination analysis 97.1 wt%, 0.98 molar time) was added dropwise with the liquid temperature kept in a range from 5 to 10C. Then, stirring was carried out at 0C for 2 hours. The reaction solution was analyzed, and as a result, the reaction yield of 1-benzyloxycarbonyl-3-methylpiperazine was 82.5%.

109-07-9, The synthetic route of 109-07-9 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Toray Fine Chemicals Co., Ltd.; EP1548010; (2005); A1;,
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With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.149057-19-2,4-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid,as a common compound, the synthetic route is as follows.

Step A: 4-Benzyl 1-(tert-butyl) 2-carbamoylpiperazine-1,4-dicarboxylate. NH4HCO3 (9 g, 114 mmol) was added to a solution of 4-((benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid (33 g, 91 mmol), Boc2O (25.7 g, 118 mmol), pyridine (4.3 g, 54 mmol), and 1,4-dioxane (462 mL). After 14 hours, the mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (300 mL) and the solution was washed with brine. The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to afford the title compound (36 g). This material was used in the next step without further purification. MS (ESI): mass calcd. for C18H25N3O5, 363.2; m/z found, 386.0 [M+Na]+.

149057-19-2, The synthetic route of 149057-19-2 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Janssen Pharmaceutica NV; Barbay, J. Kent; Chai, Wenying; Hirst, Gavin C.; Kreutter, Kevin D.; Kummer, David A.; McClure, Kelly J.; Nishimura, Rachel T.; Shih, Amy Y.; Venable, Jennifer D.; Venkatesan, Hariharan; Wei, Jianmei; (501 pag.)US2020/55874; (2020); A1;,
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With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.109-07-9,2-Methylpiperazine,as a common compound, the synthetic route is as follows.

Example 24A 3-methyl-1-pyridin-2-ylpiperazine hydrobromide 2-Methylpiperazine (1.0 g, 0.01 mol, racemic mixture) and 2-bromopyridine (10 mL, 0.1 mol) were combined and heated at 120 C. for 16 hours. The reaction mixture was cooled to 23 C. and partitioned between ethyl acetate and water. The layers were separated, and the water layer was concentrated under reduced pressure. The residue was triturated with ethyl acetate, dichloromethane, and methanol to afford 460 mg (26% yield) of the title compound as an off-white solid. 1H NMR (300 MHz, DMSO-d6) delta 1.27 (d, J=6.6 Hz, 3H), 2.90 (dd, J=10.5, 14.1 Hz, 1H), 3.10 (m, 2H), 3.40 (m, 2H), 4.32 (m, 2H), 6.77 (dd, J=4.8, 6.9 Hz, 1H), 6.98 (d, J=8.1 Hz, 1H), 7.64 (m, 1H), 8.15 (m, 1H), 8.63 (bs, 1H), 8.92 (bs, 1H); MS (APCI) m/e 178 (M+H)+.

109-07-9, The synthetic route of 109-07-9 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Cowart, Marlon D.; Bhatia, Pramila A.; Daanen, Jerome F.; Stewart, Andrew O.; Patel, Meena V.; Kolasa, Teodozyj; Brioni, Jorge D.; Rohde, Jeffrey; US2002/169166; (2002); A1;,
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278788-66-2, (R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Tert-butyl (R)-3-(hydroxymethyl)piperazine-1-carboxylate (384 mg, 1.78 mmol) was added to a mixture of 53 7-bromo-4,6-dichloro-3-nitroquinoline (260 mg, 0.81 mmol) and 56 DIPEA (0.316 ml, 1.78 mmol) in NMP (4 ml). The mixture was heated at 75 C. for 2 hours, then allowed to cool to room temperature. The mixture was partitioned between ethyl acetate (100 ml) and water (100 ml). The aqueous layer was extracted with ethyl acetate (100 ml) and the extracts combined with the organic layer. The combined organics were washed sequentially with water (2×100 ml) and saturated brine (50 ml), then dried and evaporated to dryness to give a brown gum. The crude product was purified by flash silica chromatography, elution gradient 20 to 40% 57 EtOAc in 58 heptane. Pure fractions were evaporated to dryness to afford 59 tert-butyl (R)-4-(7-bromo-6-chloro-3-nitroquinolin-4-yl)-3-(hydroxymethyl)piperazine-1-carboxylate (218 mg, 54%) as a yellow solid. 1H NMR (500 MHz, DMSO, 27 C.) 1.43 (9H, s), 3.34-3.53 (5H, m), 3.64 (3H, d), 4.34-4.42 (1H, m), 4.58 (1H, t), 8.38 (1H, d), 8.49 (1H, s), 9.05 (1H, s). m/z: ES+ [M+H]+ 501.

278788-66-2, 278788-66-2 (R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate 24820286, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; ASTRAZENECA AB; Kettle, Jason Grant; Bagal, Sharanjeet; Robb, Graeme Richard; Smith, James Michael; Goldberg, Frederick Woolf; Cassar, Doyle Joseph; Feron, James Lyman; US2019/177338; (2019); A1;,
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With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.120737-78-2,tert-Butyl 2-methylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

A mixture of ethyl 4,6-dimethyl-2-(4-methylpyridin-3-yl)pyrimidine-5-carboxylate (23)(23 mg, 85 mmol) and lithium hydroxide (50 mg, 2.09 mmol) in ethanol (3 mL) was heated at reflux for 3 h. The solvent was removed in vacuo before the residue was purified via reverse phase(C18) HPLC with a gradient elution of H2O/MeOH (100/0% to 10/90%) to afford compound 27 as an orange-brown solid (18 mg, 87%). 1HNMR (D2O, MeOD) d: 8.77 (s, 1H), 8.43 (d, J4.8 Hz, 1H), 7.39 (d,J4.8 Hz, 1H), 2.59 (s, 6H), 2.53 (s, 3H). 13C NMR (D2O, MeOD) d:170.5, 163.2, 162.6, 150.8, 149.8, 149.0, 136.3, 133.8, 127.5, 22.3, 20.4.LRMS (ESI): m/z 244.1 [MH] (100%); (ESI): m/z 242.0 [MH](100%).A solution of 4,6-dimethyl-2-(4-methylpyridin-3-yl)pyrimidine-5-carboxylic acid (27) (40 mg, 0.16 mmol), ()-tert-butyl 2-methylpiperazine-1-carboxylate45 (36 mg, 0.18 mmol), HOBt(24 mg, 0.18 mmol), EDCI (36 mg, 0.18 mmol) and DIPEA (0.08 mL,0.33 mmol) in DCM (10 mL) was stirred at room temperature for 18 h. The reaction mixture was diluted in H2O, extracted with DCM (310 mL), and the combined organic layers concentrated to 3 mL.To the solution was then added 10 drops of TFA before stirring for 3 h. The reaction mixture was then extracted with H2O (33 mL)and the combined aqueous layers freeze dried. The residue was purified via reverse phase (C18) HPLC with a gradient elution ofH2O/MeOH (100/0% to 10/90%), to afford the desired product asa pale yellow solid (4 mg, 7%) as a mixture of conformers. 1H NMR (MeOD) d: 8.44 (br s, 1H), 7.64e7.58 (m, 1H), 7.45 (m, 1H), 7.15e7.07(m, 1H), 4.59 (m, 2H), 3.95 (br s, 2H), 3.63e3.06 (complex, 6H), 2.39(br s, 3H), 1.32 (m, 3H). 13C NMR (MeOD) d: 157.0, 148.9, 147.8,139.2, 129.7, 129.4, 127.4, 127.0, 125.2, 123.4, 123.1, 113.6, 113.3, 52.0,51.9, 47.1, 30.7, 19.9, 17.1, 16.9. HRMS (APCI): m/z calcd forC18H24N5O [MH]: 326.1981, found: 326.1978; (APCI): m/z calcdfor C19H22N4O [MH]: 324.1824, found: 324.1829., 120737-78-2

The synthetic route of 120737-78-2 has been constantly updated, and we look forward to future research findings.

Reference：
Article; Lim, Zelong; Duggan, Peter J.; Wan, Soo San; Lessene, Guillaume; Meyer, Adam G.; Tuck, Kellie L.; Tetrahedron; vol. 72; 9; (2016); p. 1151 – 1160;,
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With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.78551-60-7,tert-Butyl 4-benzyl-3-oxopiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

78551-60-7, To a solution of the product of Step 8 (261 mg, 0.900 mmol) in anhydrous THF(5 ml) in a dry ice-acetone bath was added 2M LDA (0.45 ml) and the mixture wasstirred for 1 h. A solution of the above aldehyde in THF (5 ml) was added and themixture was stirred in the dry ice-acetone bath for 2 h. The reaction was quenchedwith saturated NH4CI (4 ml), diluted with CH2CI2 (50 ml), and washed with water (30ml). The organic layer was extracted with saturated NH4CI and brine, dried (MgSO4),concentrated, and purified by PTLC (5% MeOH/CH2CI2) to give the product (100 mg,48%). MS m/e 699 (M+H)+

78551-60-7 tert-Butyl 4-benzyl-3-oxopiperazine-1-carboxylate 10891590, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; SCHERING CORPORATION; WO2006/14944; (2006); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

694499-26-8,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.694499-26-8,4-((4-Methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline,as a common compound, the synthetic route is as follows.

Unit Operation 3. 1: Drying Reaction Mixture AP25047, AP24592, and 2-methyl tetrahydrofuran (2-Me-THF) are charged to a reactor. The mixture is concentrated at reduced pressure to a target volume. Additional 2-methyl tetrahdyrofuran is added and the distillation repeated. Following another charge of 2-methyl tetrahydrofuran and a distillation cycle, the water content of the mixture is determined in IPC- 1 (KF). If the IPC-1 criterion is met, the process is continued to Unit Operation 3.2. Unit Operation 3.2: Reaction The suspension is maintained with stirring at a target temperature of 13 – 23C range while potassium fe -butoxide (KOfBu) is charged. After a period of not less than 3 hours, the reaction progress is determined by HPLC (IPC-2). If the IPC criterion is met, the process is continued to Unit Operation 3.3. Unit Operation 3.3: Quench and Extractions The reaction mixture is diluted with 2-methyltetrahydrofuran (2-Me-THF), and quenched by the addition of aqueous sodium chloride solution. The organic layer is separated and the aqueous layer is extracted twice with 2-methyl tetrahydrofuran. The combined organic layers are sequentially washed with aqueous sodium chloride and water. The organic layer is then aged at 15 – 30C. Unit Operation 3.4: Concentration / Solvent Exchange After aging (see Unit Operation 3.3), the mixture is passed through a cartridge filter and concentrated under vacuum to a target volume. 1 -Propanol is charged and allowed to stir at elevated temperature to furnish a solution, which is distilled under vacuum to a target volume and then cooled slowly to a temperature range of 20 – 30C. Unit Operation 3.5: Crystallization The product solution in 1 -propanol is aged with stirring at a temperature of 20 – 30C until the presence of solids is visually observed. Acetonitrile is charged to the suspension with stirring and the resulting suspension is aged for an additional 60 – 120 minutes at 20 – 30C with agitation prior to isolation in the next Unit Operation. Unit Operation 3.6: Isolation / Drying The slurry generated in Unit Operation 3.5 is isolated under vacuum in a filter/dryer. The solids are washed twice with a mixture of 1-propanol and acetonitrile. The solids are then dried under vacuum and monitored by IPC-3 (LOD, gravimetric). If the IPC criterion is met, the product is discharged as an off-white to yellow solid and packaged in double polyethylene bags for storage at ambient temperatures.

694499-26-8 4-((4-Methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline 46838908, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; ARIAD PHARMACEUTICALS, INC.; MURRAY, Christopher, K.; ROZAMUS, Leonard, W.; CHABER, John, J.; SHARMA, Pradeep; WO2014/93579; (2014); A2;,
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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.

General procedure: To a mixture of 6a-p (1.0mmol) and K2CO3 in acetone (10mL) was added 6-(bromomethyl)-5-chloro-2-(thiophen-2-yl)-7,8-dihydroquinoline 5 (1mmol) at room temperature under stirring for 12h (monitored by TLC), After completion the reaction mixture was evaporated and extracted with ethylacetate and water, the organic layer was separated dried over anhydrous Na2SO4. and evaporated under vacuum. The resulting crude product was purified by silica gel column chromatography by using EtOAc/hexane as eluent., 59878-57-8

The synthetic route of 59878-57-8 has been constantly updated, and we look forward to future research findings.

Reference：
Article; Marvadi, Sandeep Kumar; Krishna, Vagolu Siva; Sriram, Dharmarajan; Kantevari, Srinivas; European Journal of Medicinal Chemistry; vol. 164; (2019); p. 171 – 178;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics