Heterocyclic Building Blocks-piperazine

694499-26-8, 4-((4-Methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

694499-26-8, General procedure: To a solution of 8a-e (20 mmol) and triethylamine (40 mmol) indichloromethane (20 ml), a solution of 4a-f (1.5 eq) in dichloromethane(10 ml) was added dropwise at room temperature over20 min and stirred overnight. The mixture was washed with saturatedaqueous sodium bicarbonate and brine. After removing thesolvent under reduced pressure, the crude product was purifiedby flash chromatography on silica gel, eluting with dichloromethaneand methanol (10-30%), yielding the title compounds.

As the paragraph descriping shows that 694499-26-8 is playing an increasingly important role.

Reference：
Article; Yao, Dahong; Wang, Jing; Wang, Guan; Jiang, Yingnan; Shang, Lei; Zhao, Yuqian; Huang, Jian; Yang, Shilin; Wang, Jinhui; Yu, Yamei; Bioorganic Chemistry; vol. 68; (2016); p. 112 – 123;,
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.,4318-42-7

Oxalyl chloride (47.7 kg, 375.8 mol) was added to a solution of oxazole-5-carboxylic acid (32.88 kg, 290.8 mol) in isopropyl acetate (144 kg) maintaining the temperature at 52-58 °C. The temperature was increased to 58.5 °C, stirred for 5 h and then cooled to 20 °C. The reaction mixture was added to a solution of l-(isopropyl)piperazine (41 kg, 319.8 mol) and potassium carbonate (118.4kg) in isopropyl acetate (348 kg) and water (103 kg) maintaining the temperature below 25 °C. The reaction was stirred for 15 mins, the temperature was increased to 33 °C and the organic phase washed with water (191 kg), concentrated under reduced pressure to 95 L and cooled to 20 °C. n- Heptane (157 kg) was added and the crystallisation stirred for 2 h, and the product filtered off, washed with n-heptane (157 kg) and dried under vacuum 40 °C to give the title compound (57.14 kg, 88.0percent). (0441) *H NMR (400 MHz, CDC -d) delta ppm 7.94 (s, 1 H), 7.56 (s, 1 H), 3.91-3.73 (m, 4 H), 2.75 (spt., J=6.5 Hz, 1 H), 2.63-2.52 (m, 4 H) and 1.06 (d, J=6.6 Hz, 6 H).

4318-42-7 1-Isopropylpiperazine 78013, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; CAMPOS, Sebastien Andre; PATEL, Vipulkumar Kantibhai; DALTON, Samuel Edward; (74 pag.)WO2018/29126; (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.21655-48-1,cis-2,6-Dimethylpiperazine,as a common compound, the synthetic route is as follows.,21655-48-1

Preparation 5 tert-Butyl (cis)-3,5-dimethyl-1-piperazinecarboxylate STR50 (cis)-3,5-Dimethylpiperazine (5.01 g) was dissolved in dioxan (9 ml) and water (4 ml), di-tert butyldicarbonate (9.59 g) was added and the reaction mixture was stirred at room temperature for 18 hours. The solvent was then removed under reduced pressure and the remaining aqueous solution was basified to pH 9.0 with 2N aqueous sodium hydroxide solution. The product was then extracted twice with ethyl acetate, the combined organic layers were dried over magnesium sulphate and the solvent removed under reduced pressure. The crude product was purified by column chromatography on silica gel eluding with a solvent system of 93:7:1, by volume, dichloromethane:methanol:0.88 aqueous ammonia solution to afford tert-butyl (cis)-3,5-dimethyl-1-piperazinecarboxylate (6.40 g) as a yellow liquid. 1 H-NMR (CDCl3)delta:3.90 (2H, bs), 2.80 (2H, m), 2.30 (2H, m), 1.45 (9H, s), 1.40 (1 H, bs), 1.05 (6H, d). MS:215 (MH+).

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

Reference：
Patent; Pfizer Inc; US6166011; (2000); A;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5308-25-8,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.5308-25-8,1-Ethylpiperazine,as a common compound, the synthetic route is as follows.

To a solution of compound 88 (2 g, 9.8 mmol, 1 eq) in DMSO (10 mL) was added K2CO3 (2.7 g, 19.7 mmol, 2 eq), 1-ethylpiperazine (compound 89, 1.7 g, 14.7 mmol, 1.5 eq) and TBAI (36 mg, 0.098 mmol, 0.01 eq). The reaction mixture was stirred at 120 C for 2 h. After cooling down to rt, the mixture was diluted with water (30 mL), thus formed solid was filtered, rinsed with water (5 mL x 3), and dried to afford the desired product (1.5 g, 65%) as a yellow solid which was used to the next step directly. NMR (300 MHz, CDC ): delta 8.19- 8.14 (m, 2 H), 7.23-7.19 (m, 1 H), 3.53-3.45 (m, 4 H), 2.79-2.65 (m, 4 H), 2.57-2.50 (m, 2 H), 1.19 (t, J= 7.2 Hz, 3 H).

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

Reference：
Patent; BEIJING XUANYI PHARMASCIENCES CO., LTD.; SONG, Yuntao; CHEN, Xiaoqi; (188 pag.)WO2019/35008; (2019); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

694499-26-8, 4-((4-Methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,694499-26-8

3,5-Diiodo-4-methylbenzoic acid (194.0 mg, 0.5 mmol)To the mixture is added SOCl2 (0.73 mL, 10 mmol), and a catalytic amount of DMF is added dropwise,Stir at room temperature for 20 hours. The solution is dried under vacuumIntermediate (3,5-Diiodo-4-methyl-benzoyl chloride)(178.9 mg, 0.44 mmol, 88%, white solid) were obtained.4-[(4-methyl-1-piperidinyl) methyl] -3- (trifluoromethyl) -benzenamine (94.6 mg, 0.35 mmol), N, N-diisopropylethylamine(73 muL, 0.42 mmol), DMAP (1.2 mg, 0.01 mmol) in THF (2.4 mL)Dissolved in water, to which the intermediate (170.7 mg, 0.42 mmol) is added,Stir at room temperature for 2 hours. Add water and extract with ethyl acetate,It concentrated under reduced pressure with an evaporator.The resulting residue is purified by silica gel column chromatography (chloroform: methanol = 10: 1) to give compound 1(180.0 mg, 0.28 mmol, 80%, pale yellow solid) were obtained.

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; Kyoto University; Arkray Corporation; Saji, Hideo; Kimura, Hiroyuki; Matsuda, Hirokazu; Nakanishi, Shuichi; (27 pag.)JP2019/64986; (2019); A;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

122833-04-9, 2-Methoxy-4-(4-methylpiperazin-1-yl)aniline is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

2-Methoxy-4-(4-methylpyridazin-1-yl)phenylamine (2.21 g, 1.0 eq) was added to compound l-1 (3.7 g, 1. Oeq) n-butanol (70 ml) In the solution, the reaction was carried out at 90 C for 2-3 hours. After the reaction was completed by TLC, the mixture was cooled to room temperature, filtered, washed and dried to give a red solid (4.6 g).

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

Reference：
Patent; Chengdu University; Zhao Lifeng; Gou Xiaojun; (47 pag.)CN109384788; (2019); A;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

129779-30-2, (3R,5S)-rel-tert-Butyl 3,5-dimethylpiperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To a solution of /er/-butyl (3/^,5.V)-3,5-dimethylpiperazine- 1 -carboxylate (compound Id, CAS: 129779-30-2, PharmaBlock, Catalog: PB125871, 100 mg, 467 pmol) and K2C03 (129 mg, 933 pmol) in MeCN (5 mL) was added l-bromo-4-(bromo methyl) benzene (compound le, CAS: 589-15-1, Accela ChemBio, Catalog: SY001367, 117 mg, 467 pmol). The resultant mixture was heated to 80 C for 14 hrs, then cooled to room temperature. The reaction mixture was filtered and the filter cake was washed with EA (10 mL). The combined filtrate was concentrated in vacuo and purified by flash chromatography (silica gel, 12 g, 10% to 50% EtOAc in PE). The purified intermediate was dissolved in DCM (2 mL) and TFA (0.5 mL) was added. The reaction mixture was stirred at room temperature for 3 hrs, then concentrated to afford a crude compound If, MS: calc?d 283 and 285 [(M+H)+], measured 283 and 285 [(M+H)+], 129779-30-2

The synthetic route of 129779-30-2 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; DEY, Fabian; QIU, Zongxing; ZHU, Wei; ZOU, Ge; (55 pag.)WO2020/20800; (2020); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

181955-79-3, 1,4-Di-Boc-piperazine-2-carboxylic acid is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

l54-Di(tert-butoxycarbonyl)piperazine-2-carboxylic acid (14.45 g, 43.7 mmol) was dissolved in THF (200 mL), and borane-THF complex (1.0 M solution in THF, 100 mL, 100 mmol) was added slowly. Upon complete addition, the reaction mixture was heated to 50 0C. After 2 h, the reaction mixture was allowed to cool to rt and was slowly quenched by the dropwise addition of MeOH (50 mL). After gas evolution ceased, the reaction mixture was heated to 50 0C for 1 h. Upon cooling to rt, the reaction mixture was concentrated under reduced pressure. The material was dissolved in THF (200 mL) and NaH (60% dispersion in mineral oil, 1.75 g, 43.7 mmol) was added portion wise. The reaction mixture was heated to 50 0C overnight. Upon cooling to rt, the reaction mixture was quenched with H2O (300 mL) and extracted with EtOAc (3 x 400 mL). The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The material was purified by column chromatography (10 to 40% EtOAc in Hexanes gradient) to give 6.31 g (59%) of the desired product as a white solid. Rf = 0.43 in 80% EtOAc in Hexanes. 1.10 g (8%) of di-tert-butyl 2- (hydroxymethyl)piperazine-l,4-dicarboxylate was also isolated. Rf= 0.63 in 80% EtOAc in Hexanes.; Borane-THF complex (1.0 M solution in THF, 200 mL, 200 mmol) was added slowly to a solution of l,4-bis(tert-butoxycarbonyl)piperazine-2-carboxylic acid (30.3 g, 91.7 mmol) in THF (100 mL). Upon complete addition, the reaction mixture was heated to 50 0C for 2 h. Upon cooling to rt, the reaction mixture was carefully quenched by the dropwise addition of MeOH. After gas evolution ceased, the reaction mixture was concentrated under reduced pressure. The material was dissolved in EtOAc (300 mL) and washed with 1 N NaOH (2 x 200 mL) and brine (200 mL). The organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The material was twice dissolved in THF (50 mL) and concentrated under reduced pressure. The material was dissolved in THF (200 mL) and NaH (60% dispersion in mineral oil, 0.366 g, 0.916 mmol) was added portionwise. The reaction mixture was heated to reflux. After 1 h, the reaction mixture was allowed to cool to rt and was concentrated under reduced pressure. The material was dissolved in EtOAc (300 mL), washed with water (2 x 200 mL) and brine (200 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting solid was dissolved in EtOAc (200 mL) with heating, diluted with hexanes (200 mL) and allowed to cool to rt. The white, crystalline solid was collected by filtration after 5 h, washed with hexanes (2 x), and dried under vacuum. This gave 13.29 g (60%) of the product. The filtrate was concentrated under reduced pressure, dissolved in EtOAc (50 mL) with heating, and diluted with hexanes (200 mL). This was allowed to cool to rt and sit over the weekend. The white, crystalline solid was collected by filtration, washed with hexanes (2 x), and dried under vacuum. This gave an additional 4.49 g (20%) of the product. Analytical data: Rf = 0.43 in 80% EtOAc / Hexanes; 1H NMR (400 MHz, CDC13) delta 4.41 (t, J = 8.4 Hz, IH), 4.35-3.98 (br, 2H), 3.92 (dd, J = 5.6 and 8.8 Hz, IH), 3.80-3.72 (m, 2H), 2.98 (dt, J = 3.6 and 12.4 Hz, IH), 2.86-2.70 (br, IH), 2.70-2.55, (br, IH), 1.45 (s, 9H); 13C NMR (100 MHz, CDC13) delta 156.7, 154.2, 81.1, 65.5, 52.9, 47.7 (br), 43.4 (br), 41.1, 28.7. LC-MS: RT = 6.46 min; [M+Na]+ = 264.9. Anal. Calcd for CnH18N2O4: C3 54.53; H, 7.49; N, 11.56. Found: C, 54.38; H, 7.44; N, 1 1.35.

181955-79-3, 181955-79-3 1,4-Di-Boc-piperazine-2-carboxylic acid 11255979, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; CRITICAL THERAPEUTICS, INC.; WO2007/146066; (2007); A2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

70261-82-4,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.70261-82-4,4-(4-Methylpiperazin-1-ylmethyl)phenylamine,as a common compound, the synthetic route is as follows.

EXAMPLE 119: 1 -(4-methoxybenzyl)-3-methyl-N-(4-((4-methylpiperazin- 1 – yl)methyl)phenyl)-lH-pyrazolor3,4-b1pyridin-5-amineA stirred solution of 5-bromo-l-(4-methoxybenzyl)-3-methyl-lH-pyrazolo[3,4-b]pyridine (7) (50 mg, 0.150 mmol) and 4-((4-methylpiperazin-l-yl)methyl)aniline (165) (30 mg, 0.165 mmol, 1.1 eq) in 1,4-dioxane (10 mL) was degassed and purged with N2 for 10 min. tert- uOK (50 mg, 0.451 mmol, 3.0 eq) was added and the reaction mixture was purged and degassed again. To this reaction mixture was added +/-BINAP (1.8 mg, 0.00301 mmol, 0.01 eq) and Pd2(dba)3 (5 mg, 0.0012 mmol, 0.04 eq) and the resulting reaction was heated at 90C for 12 hrs in sealed tube condition. After completion of the reaction the contents were cooled and diluted with CHC13 and filtered through Celite bed. The CHC13 layer was completely distilled off to get the crude product. The crude was passed through 100-200 mesh silica gel, eluting the pure compound 1- (4-methoxybenzyl)-3 -methyl-N-(4-((4-methylpiperazin- 1 -yl)methyl)phenyl)- lH-pyrazolo [3 ,4- b]pyridin-5 -amine 166 obtained with 6% MeOH in CH2C12 as an off-white coloured solid in 30 mg quantity.

The synthetic route of 70261-82-4 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; ARRIEN PHARMAEUTICALS LLC; VANKAYALAPATI, Hariprasad; APPALANENI, Rajendra, P.; REDDY, Y., Venkata Krishna; WO2012/135631; (2012); 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.

Step 1: (S)-tert-butyl-4-(2-cyano-3-fluorophenyl)-2-methylpiperazine-1-carboxylate To a solution of 2,6-difluorobenzonitrile (0.8 g, 5.7 mmol) in DMF (10 mL) was added (S)-tert-butyl 2-methylpiperazine-1-carboxylate (1.14 g, 5.7 mmol) and K2CO3 (2.35 g, 17.1 mmol). The solution was stirred for 17 hrs at 100 C., then concentrated to give the crude. The crude was purified by chromatography (silica, EtOAc/PE=1/10) to afford (S)-tert-butyl-4-(2-cyano-3-fluorophenyl)-2-methylpiperazine-1-carboxylate (0.6 g, 1.88 mmol, 33%) as a white solid. MS (EI+, m/z): 320 [M+H]+.

169447-70-5, The synthetic route of 169447-70-5 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Navitor Pharmaceuticals, Inc.; O’Neill, David John; Saiah, Eddine; Kang, Seong Woo Anthony; Brearley, Andrew; Bentley, Jonathan; (136 pag.)US2019/389843; (2019); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics