Month: June 2021

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.

General procedure: 4-Nitrobenzyl bromide (46.3mmol) was dissolved in dichloromethane (100mL). The solution was added to the mixture of relative amine (47.0mmol) and triethylamine (70.3mmol) in dichloromethane (20ml). The reaction mixture was stirred at r. t. for 24 h and was extracted with dichloromethane (100ml×3). After removal of the solvent, the residue was crystallized from ethanol, giving yellow powder. Compounds 1 and 2 were used for further reaction without purification. To a suspension of compounds 1-2 (36.2mmol) in 95% ethanol (100ml), 85% NH2NH2·H2O (362mmol), 95% ethanol (100ml) and iron (III) oxide hydroxide (FeO(OH)/C, 2.0g) were added and heated to reflux. When TLC analysis showed complete conversion of the starting material, the reaction mixture was filtrate through Cellit and the filtrate was concentrated in vacuum. The crude product was purified by silica gel colum chromatography (DCM/MeOH) to yield the title compound (3 and 4) as white solid. The mixture of compound 4 (1eq, 18.5mmol), 4-Nitro-1H-pyrazole-3-acid (1.1equiv, 20.4mmol), EDC (1.2equiv, 22.2mmol), HOBT (1.2equiv, 22.2mmol) in DMF (50ml) was stirred for 24h. The ice water (100ml) was added to the reaction mixture. A large amount of yellow solid precipitation (compound 8) was acquired. Compound 8 was used without further purification. Compounds 8 was reduced by the same process as compound 4, and then the resulting compound 12 was purified by column chromatography on silica gel, eluted with the appropriate solvent., 70261-82-4

As the paragraph descriping shows that 70261-82-4 is playing an increasingly important role.

Reference：
Article; Zhi, Yanle; Li, Baoquan; Yao, Chao; Li, Hongmei; Chen, Puzhou; Bao, Jiyin; Qin, Tianren; Wang, Yue; Lu, Tao; Lu, Shuai; European Journal of Medicinal Chemistry; vol. 155; (2018); p. 303 – 315;,
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.150407-69-5,(S)-1-((Benzyloxy)carbonyl)-4-(tert-butoxycarbonyl)piperazine-2-carboxylic acid,as a common compound, the synthetic route is as follows.

(b)[2S]-1-Benzyloxycarbonyl-4-t-butoxycarbonyl-2-methoxycarbonylpiperazine A solution of [2S]-1-benzyloxycarbonyl-4-t-butoxycarbonylpiperazine-2-carboxylic acid [prepared from Example 1(a) by the method of Bigge et al. Tet. Letters 30, 5193 (1989)] (16 g) in methanol (5 ml) and acetonitrile (50 ml) was treated with diisopropylethylamine (5.7 ml) and a 2M solution of trimethylsilyldiazomethane in hexane (26.3 ml) and stirred overnight at room temperature. The reaction mixture was evaporated and chromatographed on silica gel eluding with 0-10% ethyl acetate-hexane to afford the title compound as a colourless oil (9.0 g). MS (+ve ion electrospray) m/z 379 (MH+).

150407-69-5, As the paragraph descriping shows that 150407-69-5 is playing an increasingly important role.

Reference：
Patent; SmithKline Beecham Corporation and SmithKline Beecham p.l.c.; US2003/203917; (2003); A1;,
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.

2-chloro-4 (4-fluorophenyl) -5,6,7,8,9,10-hexahydrocycloocta [b] pyridine (7.4 kg)BINAP (95 g), bis (dibenzylideneacetone) palladium(44 g), sodium tert-butoxide (3.7 kg),Toluene (37 L), ethyl piperazine (8.7 kg) was charged to the reactor.The temperature was raised to T = 75 to 80 C. and maintained at T = 80 to 85 C. for 3 hours.(Note: the reaction is exothermic, typically a complete conversion is achieved after 2 hours at 80 C). The mixture was cooled to 60-65 C.,Water (37 L) was added keeping the temperature at T = 60-65 C.The temperature was adjusted to T = 70-75 C. and the layers were separated. I removed the lower aqueous layer.The organic layer was washed with brine solution (36 L). Reduce the temperature below 25 C,The organic layer was filtered through an activated carbon cartridge.The organic layer was treated with water (22 L) and hydrochloric acid (4.5 L).The layers separated and the organic layer was removed. The aqueous layer (including product) was dissolved in toluene(37 L) and sodium hydroxide (5.2 L).The temperature was adjusted to T = 70-75 C. and the layers were separated. I removed the lower aqueous layer.The solvent was removed by vacuum distillation to a small amount. Acetone (22 L) was added,The mixture was heated to reflux. Dissolution occurred and the mixture was cooled to T = 0 to 5 C. The product was isolated by filtration and washed with cold acetone.The product in the wet state is dried under vacuum at T = 48-53 C. to give a purity99.92% A% HPLC (method 2) of blonanserin was obtained(7.8 kg, molar yield 85%). Blonanserin (7.6 kg) obtained in the above procedure was recrystallized from isopropanol (purpose: blank filtering of blonanserin) (6.7 kg; yield 88%; purity 99.94% A% HPLC (method 2)).

The synthetic route of 5308-25-8 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; LUNDBECK PHARMACEUTICALS ITALY SA; HUBER, FLORIAN ANTON MARTIN; FAVERI, CARLA DE; (25 pag.)JP2018/43989; (2018); A;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5747-48-8, 11-(Piperazin-1-yl)dibenzo[b,f][1,4]thiazepine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

5747-48-8, A solution of but-3-yn-2-one (1 mmol) and PDBTZ (1 mmol), in ethyl acetate (10 mL) is refluxed for two hours. The reaction mixture is washed (water, brine), dried (sodium sulfate), and evaporated. The crude material is purified by flash chromatography to provide the enamine product.

The synthetic route of 5747-48-8 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; ASTRAZENECA AB; WO2008/79847; (2008); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

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 (1.68 g, 7.77 mmol) was added to 113 7-bromo-4,6-dichloro-8-fluoro-3-nitroquinoline (1.2 g, 3.53 mmol), and 56 DIPEA (1.571 ml, 8.83 mmol) in NMP (10 ml) under nitrogen, and the resulting solution was stirred at room temperature for 3 hours. The mixture was partitioned between ethyl acetate and water then the organic layer was washed with water (×2) then brine, dried and evaporated then purified by flash silica chromatography, elution gradient 10 to 40% 57 EtOAc in 58 heptane. Pure fractions were evaporated to dryness to afford 115 tert-butyl (R)-4-(7-bromo-6-chloro-8-fluoro-3-nitroquinolin-4-yl)-3-(hydroxymethyl)piperazine-1-carboxylate (0.96 g, 52%) as a yellow solid. m/z: ES+ [M+H]+ 521., 278788-66-2

The synthetic route of 278788-66-2 has been constantly updated, and we look forward to future research findings.

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;,
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.170911-92-9,tert-Butyl 4-(4-aminophenyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

A stirred mixture of 8-((6-chloro- lH-pyrazolo[3,4-d]pyrimidin-l- yl)sulfonyl)quinoline (0.3 g, 0.00086 mol, 1.0 eq), tert-butyl 4-(4- aminophenyl)piperazine- l-carboxylate (0.95eq), DIPEA (3.0 eq) in w-BuOH (10 mL) in a sealed vial was heated at 110C for 16 h. After TLC showed completion of the starting material, the mixture was cooled to rt, poured into water and extracted with ethyl acetate (2 x 100 mL). The organic layer was dried over Na2S04 and the solvent distilled off to get the crude product. The crude product was purified through Combiflash chromatography (silica gel) using MeOH in DCM as eluent. The desired compound was eluted at 0.8% MeOH in DCM and the concentration of the pure fractions provided tert- butyl 4-(4-((l-(quinolin-8-ylsulfonyl)- lH-pyrazolo[3,4-170911-92-9

170911-92-9 tert-Butyl 4-(4-aminophenyl)piperazine-1-carboxylate 11011301, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; ASANA BIOSCIENCES, LLC; VENKATESAN, Aranapakam M.; SMITH, Roger A.; THOMPSON, Scott K.; LAPING, Nicholas; KULKARNI, Bheemashankar; HALLUR, Gurulingappa; VISWANADHAN, Vellarkad N.; PENDYALA, Muralidhar; KETHIRI, Raghava Reddy; TYAGI, Rajiv; SIVANANDHAN, Dhanalakshmi; BAKTHAVATCHALAM, Rajagopal; WO2015/38417; (2015); 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.694499-26-8,4-((4-Methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline,as a common compound, the synthetic route is as follows.,694499-26-8

Methyl 3-azido-4-methylbenzoate (9.6 g, 0.5 mol) and 4-((4-methylpiperazine-1-substituted) methyl) -3- (Trifluoromethyl) aniline (13.7 g, 0.5 mol) was dissolved in re-distilled tetrahydrofuran (50.0 mL), and a solution of potassium tert-butoxide (16.8 g, 0.15 mol) in re-distilled tetrahydrofuran (50.0 mL) was slowly dropped. After 1 hour of reaction, the temperature was naturally raised to room temperature and the reaction was continued for 8 hours. After the reaction was completed, the solvent was spin-dried, extracted with EtOAc and water, and the organic phase was washed with saturated brine,Anhydrous Na2SO4 was dried, and the red solid obtained by silica gel column chromatography was the target product (13.5 g, yield: 61%).

The synthetic route of 694499-26-8 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Chinese Academy Of Sciences Guangzhou Bio-pharmaceutical And Health Institute; Ding Ke; Li Yupeng; Shen Mengjie; Long Huoyou; Zhang Zhang; Leng Fang; Lu Xiaoyun; (51 pag.)CN103539784; (2016); B;,
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.103-76-4,N-(2-Hydroxyethyl)piperazine,as a common compound, the synthetic route is as follows.

1 mol of N-hydroxyethylpiperazine and25% by mass aqueous solution of ammonium vinyl sulfonate (containing 1.10 mol of ammonium vinyl sulfonate)Was added to a 1000 mL four-necked flask equipped with a reflux tube,The addition reaction is carried out with sufficient stirring;The reaction was carried out at 60 C for 1.5 hours,And then gradually warming boiling reflux,And continue to react for 2.5 hours;then,The reaction was quenched to give a reaction mother liquor containing 4-hydroxyethylpiperazine ethanesulfonate.By high performance liquid chromatography,The yield of ammonium 4-hydroxyethylpiperazine ethanesulfonate was calculated to be 89.4%.A reaction mother liquor containing 0.5 mol HEPES-NH4 was placed in a 500 mL beaker,Under stirring,27.5 g of concentrated sulfuric acid (98 wt%) was slowly added dropwise at room temperature,Then stir,And acidified at 0 C for 1 hour.Into the low temperature thermostat bath, cooling to -15 ,Cooling crystallization for 0.5 hours,Remove the sodium sulfate by filtration.The filtrate was placed in a beaker,Constantly stirring,Slowly add 3.0 g of Ba (OH) 2,Reaction for 1 hour,Remove the remaining sulfate.Adding 5 g of activated carbon decolorization and filtering by filtration to obtain the filtrate,By rotary evaporation to anhydrous,To obtain a solid primary purified product.The solid was washed twice with 500 ml of methanol,500ml ethanol once,And then vacuum drying,Get high purity HEPES.

103-76-4, 103-76-4 N-(2-Hydroxyethyl)piperazine 7677, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; Shandong University of Technology; Cui Hongyou; Wang Jiangang; Zhu Liwei; Liu Ransheng; Yang Yong; Wang Yang; (8 pag.)CN104803949; (2017); B;,
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.59878-57-8,1-(Cyclopropylcarbonyl)piperazine,as a common compound, the synthetic route is as follows.

59878-57-8, To a solution of the above compound (68mg, 0.27mmol) in anhydrous DMF (2mL) under N2 at 0C were added WSC (61mg, 0.32mmol) and HOBt (43mg, 0.32mmol). The resulting mixture was stirred for 30min, then it was added with DIPEA (141mul, 0.81mmol) and 1-(cyclopropylcarbonyl)piperazine (115mul, 0.81mmol). Stirring was continued at room temperature for 20h. The residue was partitioned between water and ethyl acetate and the phases were separated. The organic layer was washed with brine, dried, filtered and evaporated. Purification by flash chromatography (CH2Cl2:MeOH 95:5) afforded 85mg (80%) of the title compound. 1H NMR (CDCl3) delta 10.88 (1H, br s); 8.18-7.95 (3H, m); 7.47 (1H, d, J=8.4Hz); 7.34-7.18 (2H, m); 6.50 (1H, m); 3.97-3.73 (4H, m); 3.88-3.72 (2H, m); 3.54-3.34 (2H, m); 1.75 (1H, m); 1.09-0.94 (2H, m); 0.90-0.64 (2H, m). Anal. Calcd for C22H21FN4O2: C, 67.33; H, 5.39; N, 14.28. Found: C, 69.86; H, 5.34; N, 13.88.

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

Reference：
Article; Cincinelli, Raffaella; Musso, Loana; Merlini, Lucio; Giannini, Giuseppe; Vesci, Loredana; Milazzo, Ferdinando M.; Carenini, Nives; Perego, Paola; Penco, Sergio; Artali, Roberto; Zunino, Franco; Pisano, Claudio; Dallavalle, Sabrina; Bioorganic and Medicinal Chemistry; vol. 22; 3; (2014); p. 1089 – 1103;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

55121-99-8, (4-Aminophenyl)(4-methylpiperazin-1-yl)methanone is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,55121-99-8

Example 164 N-[4-(4-Methylpiperazin-1-ylcarbonyl)phenyl]-(2-chloro-5-nitrophenyl)carboxamide The title compound (0.54 g, yield 89%) was obtained according to the procedure described in Example 2 using 4-(4-methylpiperazin-1-ylcarbonyl)aniline (0.33 g, 1.50 mmol), DMA (5 ml) and 2-chloro-5-nitrobenzoyl chloride (0.40 g, 1.80 mmol). 1H-NMR (400 MHz, DMSO-d6, TMS): delta(ppm) 2.32 (4H, m), 3.34-3.59 (4H, m), 7.42 (2H, d, J=8.6 Hz), 7.77 (2H, d, J=8.6 Hz), 7.91 (1H, d, J=8.8 Hz), 8.35 (1H, dd, J=2.7, 8.8 Hz), 8.49 (1H, d, J=2.7 Hz), 10.89 (1H, s); MS(FAB) m/z: 403 (M+H)+.

The synthetic route of 55121-99-8 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; SANKYO COMPANY, LIMITED; US2003/134859; (2003); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics