Heterocyclic Building Blocks-piperazine

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.21043-40-3,1-Cyclopentylpiperazine,as a common compound, the synthetic route is as follows.

4-Cyclopentyl-piperazine-1-carboxylic Acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl Ester. The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-cyclopentyl-piperazine. White solid, m.p. 294-295 C.; HPLC-MS m/z=436 (M+H), Rt: 2.92 min.; 1H NMR (DMSO-d6): delta 11.15 (br, 1H, NH), 8.60-8.55 (br, 1H, py-H6), 8.29-8.20 (m, 1H, py-H4), 7.32-7.21 (d+br s, 5H, py-H3+C6H4), 4.35-3.98 (br, 2H), 3.72-3.37 (br m, 5H), 3.29-2.97 (br, 2H), 2.12-1.45 (br m, 8H).

21043-40-3, The synthetic route of 21043-40-3 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Ebdrup, Soren; de Jong, Johannes Cornelis; Jacobsen, Poul; Hansen, Holger Claus; Vedso, Per; US2003/166644; (2003); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

1403898-64-5, (2R,5R)-tert-Butyl 5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To a solution of 6-(4-fluorobenzyl)-3,3,4-trimethyl-2,3-dihydro-lH-pyrrolo[3,2-b]pyridin-5(4H)-one (190 mg, 0.66 mmol) in DCM (3.00 mL) and was added triethylamine (0.277 mL, 1.99 mmol) and the reaction was stirred at room temperature under an atmosphere of nitrogen. Chloroacetyl chloride (0.058 mL, 0.730 mmol) was added and the reaction was stirred at room temperature for 30 minutes. The reaction was diluted in 25 mL DCM and washed with 10 mL saturated sodium bicarbonate solution, 10 mL water and 10 mL brine. The organic layer was passed through a biotage phase separator and concentrated under vacuum. The residue was dissolved in 3 mL THF and triethylamine (0.28 mL, 1.99 mmol) and (2R,5R)-tert-butyl 5-(hydroxymethyl)-2-methylpiperazine-l- carboxylate (199 mg, 0.86 mmol, obtained as described in WO 2012/143726) was added. The reaction was stirred at 60C for 18h, then was diluted in 25 mL EtOAc and washed with 2 x 10 mL water and 10 mL brine. The organic layer was passed a through biotage phase separator and concentrated under vacuum to afford the title compound (170 mg, 0.31 mmol, 46 % yield). LCMS Method A RT= 0.84 min, ES+ve 557.

1403898-64-5, 1403898-64-5 (2R,5R)-tert-Butyl 5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate 71003242, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; CASILLAS, Linda N.; HARLING, John David; MIAH, Afjal Hussain; SMITH, Ian Edward David; RACKHAM, Mark David; (204 pag.)WO2017/182418; (2017); A1;,
Piperazine – Wikipedia
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

mCPBA (<77% pure) (5.24 mg, assumed 0.023 mmol) in DCM (0.5 mL) was added to a stirred solution of N- ( 6 - (2,6 -dichlorophenyl ) -2 - (methylthio) -5 -oxo-5 , 6 -dihydropyrido [4 , 3 -d] pyrimidin- 8 - yl) acetamide (8.0 mg, 0.020 mmol) in toluene (1.0 mL) at RT under nitrogen. After 30 min, DIPEA (10.6 muiota, 0.061 mmol) and tert-butyl 4- (4 -aminophenyl ) piperazine-l-carboxylate (6.2 mg, 0.022 mmol) [commercially available] in toluene (0.5 mL) were added, successively, and the temperature was increased to 60 C. After 16 h, the reaction mixture was allowed to cool to RT, and was loaded onto a KP-NH column and purified by flash chromatography (0-100%, EtOAc in cyclohexane) to give the title compound (3.7 mg, 29%) as a yellow solid. LCMS (Method A): RT = 1.39 min, m/z = 624, 626 [M+H]+., 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; ALMAC DISCOVERY LIMITED; O’DOWD, Colin Roderick; ROUNTREE, James Samuel Shane; BURKAMP, Frank; WILKINSON, Andrew John; WO2014/167347; (2014); 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.75336-86-6,(R)-2-Methylpiperazine,as a common compound, the synthetic route is as follows.

General procedure: To a stirred mixture of homopiperazine (0.60 g, 6.00 mmol), 4-fluorobenzaldehyde (0.60 g, 5.00 mmol) in DCM (15 mL) wasadded AcOH (0.08 mL, 0.50 mmol) and the mixture was stirred atroom temperature for 0.5 h. Then sodium triacetoxyborohydride(1.60 g, 7.50 mmol) was added in portions. The reaction was stirredat the same temperature for 6 h. Finally, the mixture was dilutedwith saturated aqueous NaHCO3 (15.00 mL) followed by water(15.00 mL) and extracted with EtOAc (3 15.00 mL). The organiclayer was dried (MgSO4), filtered, and concentrated in vacuo. Theresidue was purified by column chromatography on silica gel (EtOAc/PE 5:1) to afford yellow oil (0.90 g, yield 77percent)., 75336-86-6

As the paragraph descriping shows that 75336-86-6 is playing an increasingly important role.

Reference：
Article; Hu, Suwen; Wang, Zhilong; Hou, Tingjun; Ma, Xiaodong; Li, Jing; Liu, Tao; Xie, Xin; Hu, Yongzhou; Bioorganic and Medicinal Chemistry; vol. 23; 5; (2015); p. 1157 – 1168;,
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.115761-79-0,1-(2,4-Difluorophenyl)piperazine,as a common compound, the synthetic route is as follows.

1- (2, 4-Difluoro-phenyl) -piperazine (3.3 mmol; prepared by reacting piperazine with 1-BROM-2, 4-difluorobenzene according to the procedure described in WO 01/92264) was dissolved in 20 mL of THF and 1.1 eq. OF PROPARGYL bromide was added, followed by [how much?] eq. of anhydrous K2CO3. The reaction mixture was stirred at room temperature for 18 hours. It was then diluted with EtOAc and washed with brine, dried with Na2SO4 and concentrated to afford 1-(2, 4-difluoro-phenyl) -4-prop-2- ynyl-piperazine., 115761-79-0

The synthetic route of 115761-79-0 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; BIOGEN IDEC MA INC.; WO2004/92171; (2004); 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.163765-44-4,(R)-1-Boc-3-Methylpiperazine,as a common compound, the synthetic route is as follows.

General procedure: To a stirred solution of 39 (5.0 g, 13.5 mmol) in DMF (42 mL) were added triethylamine (3.8 mL) and 1-(pyridin-3-ylmethyl)-piperazine (3.2 g, 18.1 mmol) at room temperature under nitrogen. The stirred mixture was heated at 50C for 3 h. The reaction mixture was cooled to room temperature and diluted with water, THF and EtOAc. The organic extract was washed with water, dried over Na2SO4, filtrated and then concentrated. The crude solid was washed with Et2O/EtOAc and filtrated to afford the title compound 40 as a white solid (6.33 g, 12.4 mmol, 91.5%)., 163765-44-4

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

Reference：
Article; Nagao, Satoshi; Yamane, Yoshinobu; Funasaka, Setsuo; Tanaka, Keigo; Miyazaki, Kazuki; Kotake, Yoshihiko; Kamata, Jun-Ichi; Watanabe-Miyano, Saori; Toyama, Osamu; Ozawa, Yoichi; Mizui, Yoshiharu; Okamoto, Kiyoshi; Ito, Daisuke; Bioorganic and Medicinal Chemistry; vol. 22; 19; (2014); p. 5513 – 5529;,
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.21043-40-3,1-Cyclopentylpiperazine,as a common compound, the synthetic route is as follows.

Combine 6- (4-formyl-phenoxy)-nicotinamide (compound of example 332, step 1) (0.303 g, 1.25 mmol) and 1-cyclopentyl piperazine (0.198 g, 1.28 mmol) in methanol (11 ML) and stir. After 15.5 h, add sodium borohydride (0.109 g, 2.88 mmol), and stir at ambient temperature. After 1 h, concentrate the reaction mixture and purify by silica gel chromatography (ethyl ACETATE- 4: 1 ethyl acetate: methanol) to provide 0.172 g (36%) of the title compound as an off white solid: high resolution mass spectrum (electrospray): M . TALC for C22H29N402 381. 2291, found 381.2306 ; 1H NMR (DMSO-D6) : 8.66 (d, 1H, J = 2. 4 HZ), 8. O0 (dd, 1H, J = 2. 9,8. 8 Hz), 7.48-7. 43 (M, 2H), 7.18-7. 13 (m, 2H), 7.04 (d, L H, J = 7.8 Hz), 3.61 (s, 2H), 3.00-2. 25 (m, 9H), 2.01-1. 88 (m, 2H), 1.82-1. 69 (m, 2H), 1.69-1. 56 (m, 2H), 1.53-1. 38 (m, 2H).

21043-40-3, The synthetic route of 21043-40-3 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; ELI LILLY AND COMPANY; WO2004/26305; (2004); 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.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