Month: July 2021

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.76003-30-0,1-Boc-2-methyl-3-oxopiperazine,as a common compound, the synthetic route is as follows.

76003-30-0, To a heterogeneous mixture of Lawesson’s reagent (2.11 g, 5.06 mmol) in toluene (18 mL) was added the product of Example 1, step a (1.01 g, 4.73 mmol). The mixture was heated at 80 C for 1 h and then concentrated in vacuo. The residue was dissolved in DCM and filter loaded on Si02 column eluting with EtO Ac/Hex to afford the desired product as an orange solid (1.12 g, 100%).

The synthetic route of 76003-30-0 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; JANSSEN PHARMACEUTICA NV; ANDRES GIL, JOSE IGNACIO; LETAVIC, MICHAEL A; RECH, JASON C; RUDOLPH, DALE A; SOYODE-JOHNSON, AKINOLA; CHROVIAN, CHRISTA C; (158 pag.)JP2017/527588; (2017); 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.70261-81-3,1-Methyl-4-(4-nitrobenzyl)piperazine,as a common compound, the synthetic route is as follows.

70261-81-3, To a 0 0C cooled solution of 4-nitrobenzaldehyde in DCM (40 mL) was added Na(OAc)3BH (10.526gm, 49.66 mmol) and the reacton was stirred for lOmin. To the reaction mixture was added N-methylpiperazine (9.93 g, 99.3 mmol) under nitrogen atmosphere and the reaction mixture was continued stirring at room temperature for 4h. The progress of the reaction was monitored by TLC and upon completion of the reaction, the mixture was partitioned between DCM (20 mL) and water (15 mL) and the organic layer was separated, washed with water (2 x 15 mL), dried over sodium sulphate, filtered and the solvent was removed under reduced pressure to give crude residue. Washing with ether gave l-methyl-4-(4-nitrobenzyl)piperazine (4 g). 1H NMR (CDCl3, 200MHz) delta: 8.19 (2H, d, J= 8.4Hz), 7.53 (2H5 d, J= 8.4 Hz)5 3.59 (2H, s), 2.47 (8H, bm), 2.29 (3H5 s); m/e = 236 (M+l). To a solution of l-methyl-4-(4-nitrobenzyl)piperazine (4.0 g) in methanol (100 niL) at room temperature under nitrogen atmosphere was added Raney nickel (1.6gm). The reaction mixture was stirred for 2 hr under hydrogen atmosphere. The progress of the reaction was monitored by TLC and upon completion of the reaction, the mixture was filtered under nitrogen atmosphere and the solvent was removed under reduced pressure to give 4-[(4-methylpiperazin-l-yl)methyl]aniline (3.2 g). 1H NMR (CDCl3, 200MHz) delta: 7.13 (2H, d, J= 8.4 Hz)5 6.61 (2H, d5 J= 8.4 Hz), 3.41 (2H, s), 2.45 (8H, bm), 2.27 (3H, s); m/e = 206 (M+l).To a stirred solution of 4-[(4-methylpiperazin-l-yl)methyl]aniline (3.2 g, 15.57 mmol) in acetic acid: concentrated HCl (32:32 niL) at 10 0C was added NaNO2 (1.30 g,18.78 mmol) in water (16 mL) and stirred for 10 min. Freshly prepared SnCl2^H2O (11.75 g, 51.97 mmol) in concentrated HCl (32 mL) was added at 10 0C. The temperature of the reaction mixture was allowed to rise to room temperature and maintained there for 4hr. After filtering the reaction mixture, the precipitate was washed with water and the solid obtained was dried under reduced pressure to obtain l-(4-hydrazmobenzyl)-4- methylpiperazine (3.4 g). 1HNMR (CD3OD, 200MHz) delta: 7.66 (2H, d, J= 8.4 Hz), 7.13 (2H, d, J= 8.4 Hz), 4.46 (2H, s), 3.72 (8H5 bm), 3.11 (3H5 s);To a solution of l-(4-hydrazinobenzyl)-4-methylpiperazine (3.4 g, 13.25 mmol) in ethanol (50 mL) were added piperidone. HCl (2.51 g, 18.55 mmol). The reaction temperature was raised to 90 0C and continued stirring for 2 hrs. The progress of the reaction was monitored by TLC and upon completion of the reaction the mixture was cooled to rt and HCl gas was bubbled through the reaction mixture at 0 0C. After the reaction mixture was saturated with HCl, the temperature was raised to 90 0C again and continued stirring for 2hrs. The ethanolic HCl was removed under reduced pressure and the pH of the reaction mixture was adjusted to 12.0 with 10% NaOH solution. The mixture was partitioned between 20% MeOH: DCM and water (35 mL) and the organic layer was separated, dried over Na2SO4 filtered and the solvent was removed under reduced pressure to give crude residue. Washing with ether gave 8-[(4-methylpiperazin-l-yl)methyl]-2,3,4,5- tetrahydro-lNo.-pyrido[4,3-&]indole (1 g). 1HNMR(CD3OD5 200MHz) delta: 7.31 (IH, s), 7.27 (IH, d, J= 8.6 Hz), 7.06 (IH, d, J= 8.6 Hz), 4.01 (2H5 s), 3.60 (2H, s), 3.21 (8H5 bm), 2.86 (4H5 m), 2.28 (3H, s); m/e = 285 (M+l).To a solution of 8-[(4-methylpiperazin-l-yl)methyl]-2,3,4,5-tetrahydro-li- pyrido[4,3-delta]indole(0.5 g,1.76 mmol) in DMF (15 mL) at rt was added Example 7 (0.567 g, 2.64 mmol) and K2CO3 (0.731 g, 5.28 mmol). The reaction temperature was raised to 100 0C and continued stirring for 12hr. The progress of the reaction was monitored by TLC and upon completion of the reaction DMF was removed under reduced pressure. The reaction mixture was partitioned between ethyl acetate (100 mL) and water (80 mL) and the organic layer was separated, dried over sodium sulphate, filtered and the solvent was removed under reduced pressure to give crude residue. Washing with ether gave methyl 2-{8-[(4- methylpiperazin-1 -yl)methyl]-l 53s4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5- carboxylate (0.15 g). 1HNMR (DMSO-D6, 200MHz) delta: 8.84 (2H, s), 7.94 (lH,s), 7.67 (IH, d, J= 8.6 Hz), 7.54 (IH, d, J= 8.6 Hz), 5.01 (2H, s), 3.80-3.01 (1OH, m), 2.87 (3H, s); m/e = 421 (M+l).To a 00C solution of methyl 2-{8-[(4-methylpiperazin~l-yl)methyl]-l,3,4,5- tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxylate (0.1 g) in MeOH: DCM (5:2 mL) was added 50% aqueous hydroxylamine solution (2 mL) and to the mixture was added a solution of NaOH (0.08 g) in water (1 mL). The reaction mixture was stirred at room temperature for lhr and the progress of the reaction was monitored by TLC and upon completion of the reaction the solvent was removed under reduced pressure. The pH of the mixture was adjusted to 7.5 using IN HCl and the obtained solid was filtered and washed with water followed by diethyl ether. After filtering, t…

70261-81-3 1-Methyl-4-(4-nitrobenzyl)piperazine 677795, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; MIKANA THERAPEUTICS, INC.; WO2006/88949; (2006); 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.21091-98-5,(4-Methylpiperazin-1-yl)(4-nitrophenyl)methanone,as a common compound, the synthetic route is as follows.

General procedure: To a stirring solution of compound 4a (1.2g, 4.77mmol) in 70% ethanol (20mL) were added ammonium chloride (1.28g, 23.85mmol) and reduced iron powder (0.8g, 14.31mmol). The reaction was refluxed for 5h. Upon completion, the mixture was filtered while hot and rinsed with ethyl acetate. The solvent was removed in vacuo, and the residue was purified by silica gel column chromatography (PE : EA=1 : 2) to afford compound 5a as an orange solid.

21091-98-5, The synthetic route of 21091-98-5 has been constantly updated, and we look forward to future research findings.

Reference：
Article; Heng, Hao; Wang, Zhijie; Li, Hongmei; Huang, Yatian; Lan, Qingyuan; Guo, Xiaoxing; Zhang, Liang; Zhi, Yanle; Cai, Jiongheng; Qin, Tianren; Xiang, Li; Wang, Shuxian; Chen, Yadong; Lu, Tao; Lu, Shuai; European Journal of Medicinal Chemistry; vol. 176; (2019); p. 248 – 267;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

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

To a solution of tert-butyl (3S)-3-ethylpiperazine-l -carboxylate (0.5 g, 2.3 mmol) and 2-amino-4,6-dichloropyrimidine-5-carbaldehyde (0.45 g) in 1,4-dioxane (8.0 mL) was added DIPEA (1.2 mL, 7.0 mmol). The reaction mixture was heated at 120C overnight in a sealed Wheaton vial, then cooled and stirred at room temperature over the weekend. The solvent was removed in vacuo, and the residue was partitioned between water and DCM. The organic layers were phase separated and concentrated in vacuo to give the title compound (0.85 g, 99%) as a yellow glass. LCMS (ES+) [M+H]+ 370, RT 1.81 minutes (method 2).

As the paragraph descriping shows that 928025-56-3 is playing an increasingly important role.

Reference：
Patent; UCB PHARMA S.A.; KATHOLIEKE UNIVERSITEIT LEUVEN, K.U.LEUVEN R&D; FORD, Daniel James; FRANKLIN, Richard Jeremy; GHAWALKAR, Anant Ramrao; HORSLEY, Helen Tracey; HUANG, Qiuya; REUBERSON, James Thomas; VANDERHOYDONCK, Bart; WO2014/96423; (2014); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

59702-07-7, 1-Methylpiperazin-2-one is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

59702-07-7, This compound was prepared according to the procedure described for the synthesis of Example 187 using methylpiperazin-2-one in place of L-proline-tert-butyl ester. Into a 50-mL round-bottom flask, was placed a solution of (S)-N1-methyl-N1-(2-oxoethyl)-N3-(4-(piperidin-1-yl)-2-(4-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenyl)isophthalamide (100 mg, 0.16 mmol, 1.00 equiv) in ethanol (2 mL). This was followed by the addition of a solution of 1-methylpiperazin-2-one (18 mg, 0.16 mmol, 1.00 equiv) in ethanol (2 mL), two drop of acetic acid. To this was added NaBH3CN (20 mg, 0.32 mmol, 2.00 equiv). The resulting solution was stirred for 2 h at room temperature. The resulting solution was diluted with 50 mL of ethyl acetate. The resulting mixture was washed with 2*20 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product (100 mg) was purified by Prep-HPLC with the following conditions (1No.-Waters 2767-3): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05percent TFA and CH3CN (22percent CH3CN up to 38percent in 6 min); Detector, Waters2545 UvDector 254&270 nm. 70 mg product was obtained. This resulted in 70 mg (61percent) of (S)-N1-methyl-N1-(2-(4-methyl-3-oxopiperazin-1-yl)ethyl)-N3-(4-(piperidin-1-yl)-2-(4-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenyl)isophthalamide as a yellow solid. LC-MS (ES, m/z): 728 [M+H]+ H-NMR (300 MHz, DMSO, ppm): 12.25 (s, 1H), 9.18 (d, J=8.4 Hz, 1H), 8.80 (d, J=5.1 Hz, 1H), 8.29 (d, J=13.8 Hz 2H), 7.99 (t, J=6.9 Hz, 2H), 7.86 (d, J=4.8 Hz, 1H), 7.57-7.67 (m, 3H), 7.10-7.28 (m, 5H), 5.25 (d, J=5.4 Hz, 1H), 3.92-3.85 (m, 4H), 3.30-3.54 (m, 10H), 2.78-2.95 (m, 9H), 1.99 (d, J=3.6 Hz, 2H), 1.72-1.80 (m, 6H), 1.60 (s, 2H).

The synthetic route of 59702-07-7 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Ardelyx, Inc.; Lewis, Jason G.; Jacobs, Jeffrey W.; Reich, Nicholas; Leadbetter, Michael R.; Bell, Noah; Chang, Han-Ting; Chen, Tao; Navre, Marc; Charmot, Dominique; Carreras, Christopher; Labonte, Eric; (323 pag.)US9301951; (2016); B2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

161357-89-7, 1-(Methylsulfonyl)piperazine hydrochloride is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

General procedure: 0.20 mL of 2 N NaOH was added to a solution of 31 (46 mg, 0.10 mmol), prepared in a similar manner as described for 10c, in 2 mL of THF. The resulting medium was refluxed for 5 h. Additional 0.20 mL of 2 N NaOH was added to the reaction solution. Then the reaction was stirred for another 3 h under reflux. After concentration, the remaining residue was acidified to pH 2-3 by adding 1 N HCl and extracted with EA. The organic layer was dried over anhydrous Na2SO4 and concentrated under vacuum to give a crude acid (43 mg). The crude acid was dissolved in 2 mL of DMF and the solution was cooled in an ice bath. To the solution was successively added HATU (0.10 mmol), DIPEA (36 muL, 0.20 mmol) and dimethylamine hydrochloride (10 mg, 0.12 mmol). The resulting medium was stirred at room temperature for 1 h and quenched with 2 mL of saturated NaHCO3. The mixture was extracted with 50 mL of EA. The organic layer was washed with water (2 × 10 mL), brine, dried over anhydrous Na2SO4 and concentrated under vacuum. The crude product was purified by flash column chromatography (0-3% MeOH/EA gradient) to afford compound 10g in 48% yield., 161357-89-7

161357-89-7 1-(Methylsulfonyl)piperazine hydrochloride 16265612, apiperazines compound, is more and more widely used in various fields.

Reference：
Article; Zhang, Dengyou; Zhang, Xiaowei; Ai, Jing; Zhai, Yun; Liang, Zhongjie; Wang, Ying; Chen, Yi; Li, Chunpu; Zhao, Fei; Jiang, Hualiang; Geng, Meiyu; Luo, Cheng; Liu, Hong; Bioorganic and Medicinal Chemistry; vol. 21; 21; (2013); p. 6804 – 6820;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

75336-86-6, (R)-2-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Example 26A (3R)-3-methyl-1-pyridin-2-ylpiperazine (R)-(-)-2-Methylpiperazine (0.50 g, 0.005 mol, Aldrich) and 2-bromopyridine (5 mL, 0.05 mol) were combined and heated at 120° C. for 14 hours. The reaction mixture was allowed to cool to 23° C. and partitioned between a large volume of ethyl acetate and water. The layers were separated, and then additional water was added to the ethyl acetate solution. Drops of 1 N HCl solution were added to the water/ethyl acetate mixture with vigorous mixing. The layers were separated, and the combined aqueous phases were basified to pH ~11 with a solution of saturated sodium bicarbonate and solid sodium carbonate. Sodium chloride was added, and the saturated aqueous solution was extracted with chloroform containing a few drops of isopropyl alcohol (5*). The combined organic extracts were dried over Na2SO4, filtered, and the filtrate concentrated under reduced pressure to afford 0.79 g (89percent yield) of the title compound. 1H NMR (400 MHz, DMSO-d6) delta 1.02 (d, J=6.0 Hz, 3H), 2.27 (dd, J=10, 12 Hz, 1), 2.67 (m, 3H), 2.92 (m, 1H), 4.07 (m, 2H), 6.58 (dd, J=6, 8 Hz, 1H), 6.77 (d, J=8 Hz, 1H), 7.49 (m, 1H), 8.08 (m, 1H); MS (ESI) m/e 178 (M+H)+.

75336-86-6, The synthetic route of 75336-86-6 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Abbott Laboratories; US6960589; (2005); B2;,
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.120737-78-2,tert-Butyl 2-methylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

Preparation of tert-buty 4-(4-(3-(lH-indol-5-yl)-l-tosyl-lH-pyrrolo[2,3-6]pyridin-5- yl)benzyl)-2-methylpiperazi -l-carboxylate[0411] Intermediate 1 (50 mg) was dissolved in anhydrous dichloromethane (3 mL) and treated with 41 mg of tert-butyl 2-methylpiperazine-l-carboxylate. To the resulting solution was added activated 4 A molecular sieves, and the mixture was stirred 2 hrs at room temperature. 33 mg of sodium triacetoxy borohydride was added, and the reaction was stirred overnight, after which it was diluted with dichloromethane, washed with water and brine, and dried over MgS04 to yield the title compound., 120737-78-2

120737-78-2 tert-Butyl 2-methylpiperazine-1-carboxylate 15087784, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; UNIVERSITY OF ROCHESTER; GELBARD, Harris, A.; DEWHURST, Stephen; GOODFELLOW, Val, S.; WIEMANN, Torsten; RAVULA, Satheesh, Babu; LOWETH, Colin, J.; WO2011/149950; (2011); A2;,
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.

Benzyl piperazine-1-carboxylate (1.00 g, 4.54 mmol) and K2CO3 (1.255 g, 9.08 mmol) were dissolved in acetonitrile (12.87 ml) to form a suspension. 1-bromo-2-chloroethane (2.3 ml, 27.24 mmol) was added to the reaction mixture at r.t and the resulting mixture was stirred at this temperature for 96 hours.The reaction mixture was filtered, and the filtrate concentrated under reduced pressure.Purification by column chromatography (ISCO, silica gel column, eluting with 0?100percent EtOAc in hexanes) gave the title compound (0.64 g, yield: 50percent).1H NMR (300 MHz, CHLOROFORM-d) d ppm 7.28-7.43 (m, 5H) 5.15 (s, 2H) 3.48-3.65 (m, 6H) 2.76 (t, 2H) 2.42-2.57 (m, 4H).LCMS: (ESI) m/z 283 [M+H]+.

31166-44-6, The synthetic route of 31166-44-6 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; ASTRAZENECA AB; US2012/35134; (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.1403898-64-5,(2R,5R)-tert-Butyl 5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

A mixture of (2R ,5R)-5-hydroxymethyl-2-methyl-piperazine- 1 -carboxylic acid tert-butyl ester(which may be prepared as described in Preparation 4) (3.48 g, 15.1 mmol), benzaldehyde(1.76 g, 16.6 mmol), sodium triacetoxyborohydride (3.84 g, 18.1 mmol) and 1,2-dichloroethane(30 mL) was stirred at 20 C for 18 h, then partitioned between saturated aqueous NaHCO3(150 mL) and DCM (3 x 50 mL). Combined organic extracts were dried (Na2SO4) thenevaporated in vacuo to give an oil. Chromatography (Si02, 0 – 30% EtOAc in petrol) gave the title compound (4.588 g, 74%) as a colourless solid. MS: [M+H] = 321., 1403898-64-5

As the paragraph descriping shows that 1403898-64-5 is playing an increasingly important role.

Reference：
Patent; ASTEX THERAPEUTICS LIMITED; CHESSARI, Gianni; JOHNSON, Christopher Norbert; HOWARD, Steven; DAY, James Edward Harvey; BUCK, Ildiko Maria; GRIFFITHS-JONES, Charlotte Mary; SAXTY, Gordon; TAMANINI, Emiliano; WILSHER, Nicola Elisabeth; WO2015/92420; (2015); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics