Month: June 2021

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 15 A 2-liter four-neck flask with a thermometer, condenser and stirrer was charged with 200.4 g (= 2.00 moles) of racemic 2-methylpiperazine, 280.0 g of water and 96.0 g of methanol for perfect dissolution. Then, 300.4 g of 50 wt% D-tartaric acid aqueous solution (150.2 g = 1.000 mole of D-tartaric acid) was added at 40 to 45C, and the temperature was further raised up to 72C, being followed by addition of 120.2 g (= 2.00 moles) of acetic acid and aging at the temperature for 2 hours. The solvent composition was water/methanol = 81.8/18.2 (ratio by weight), and the amount of the solvent based on the racemic 2-methylpiperazine was 2.63 times by weight. Then, cooling was carried out down to 25C, taking 12 hours, and precipitated crystals were collected by filtration. The obtained crystals were dried in vacuum, to obtain 214.8 g (= 0.858 mole) of a diastereomer salt. The optical purity of the salt was 93.9%ee, and the yield of the S-isomer in the obtained salt based on the amount of the S-isomer in the supplied (+/-)-2-methylpiperazine was 83.2%. Subsequently, a 1-liter flask was charged with 380 g of water, and the obtained 214.8 g of crystals {pure (S)-2-methylpiperazine content = 83.4 g} were added. Perfect dissolution was achieved at 80 to 85C, and cooling was carried out down to 15C, taking 12 hours. Precipitated crystals were collected by filtration and dried in vacuum to obtain 187.2 g of a salt. Its optical purity was 99.4%ee, and the yield of the S-isomer in the obtained salt based on the amount of (S)-2-methylpiperazine in the supplied crystals was 89.8%. A 500 ml four-neck flask with a thermometer, condenser and stirrer was charged with 150 g of water, and 185.0 g of (S)-2-methylpiperazine D-tartaric acid salt (= 0.739 mole, optical purity of 2-methylpiperazine = 99.4%ee) obtained before and 69.1 g (= 0.863 mole) of 95% pure calcium hydroxide were added. The slurry was heated up to 70 to 80C, and stirred for 3 hours, then being cooled to room temperature. Subsequently, the non-dissolved salt was filtered away, to obtain the mother liquor. The mother liquor was GC-analyzed, and as a result, it was found that 68.7 g (= 0.686 mole) of optically active 2-methylpiperazine existed in the mother liquor (yield 92.8%). Furthermore, as a result of HPLC analysis, the optical purity of (S)-2-methylpiperazine was 99.4%ee. Then, water was distilled away till about 50 wt% was reached, being followed by addition of 1-butanol, and azeotropic dehydration was carried out till the water content of the system became less than 1 wt%. In a 1-liter four-neck flask, 50.0 g of the (S)-2-methylpiperazine (= 0.499 mole, optical purity 99.4%ee) obtained before was placed, and 440 g of 1-butanol was added for dissolution. The solution was cooled down to 0C, and 92.5 g (= 0.534 mole) of benzyl chlorocarbonate was added dropwise with the liquid temperature kept in a range from 0 to 8C. Then, stirring was carried out at 0C for 2 hours, and 300 g of 1-butanol was distilled away under reduced pressure, being followed by addition of 300 g of water. Subsequently 35% hydrochloric acid water was used to adjust the pH to 1.0, and 220 g of toluene was added, being followed by stirring for 30 minutes. The upper layer was then removed, and the same amount of toluene was added again. The same operation was repeated to carry out washing operation. Subsequently 48% sodium hydroxide aqueous solution was used to adjust the pH of the reaction solution to 12.1. In this case, white turbidity occurred due to liberated 1-benzyloxycarbonyl-3-methylpiperazine. To the white turbid solution, 400 g of toluene was added, and stirring water carried out for 30 minutes. The lower layer was then removed, and the upper layer was concentrated under reduced pressure at 60 to 70C in temperature. Subsequently toluene was distilled away to obtain 88.5 g of a concentrate. Eighty five point .zero grams of the obtained 1-benzyoxycarbonyl-3-methylpiperazine was fed to a thin film distiller (heating surface area 0.02 m2) using a liquid feed pump at 0.6 liter/h. The temperature of the heating medium was 150C, and a low-boiling component was cut at a vacuum degree of 360 Pa, to obtain 82.8 g of a liquid remaining in the distiller. The liquid remaining in the distiller was again fed to the same thin film distiller at 0.6 liter/h using a liquid feed pump. The temperature of the heating medium was 220C, and product distillation was carried out at 87 to 116 Pa in vacuum degree, to obtain 76.1 g of a distillate. The obtained compound was analyzed. As a result, the intended 1-benzyloxycarbonyl-3-methylpiperazine accounted for 99.4 liquid chromatography area %. The impurities showed 0.25 liquid chromatography area % for benzyl alcohol, 0.03 liquid chromatography area % for 1-benzyl-4-benzyloxycarbonyl-2-methylpiperazine, 0.02 liquid chromatography area % for 1-benzyl-2-methylpiperazine and no detection for 1,4-dibenzyloxycarbonyl-2-methylpiperazine (and 0.08 area % for sol…, 109-07-9

109-07-9 2-Methylpiperazine 66057, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; Toray Fine Chemicals Co., Ltd.; EP1548010; (2005); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5308-25-8, 1-Ethylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Methyl 4-fluorobenzoate (4.6 g, 29.7 mmol) was dissolved in DMSO (20 mL), followed by the addition of K2CO3 (12.3 g, 89.1 mmol) and 1-ethylpiperazine (7.6 mL, 59.4 mmol). The mixture was heated to 110 C and stirred for 10 h before being cooled to room temperature and diluted with water (50 mL) and EtOAc (200 mL). The organic phase was washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated. The residue was purified by silica gel column chromatography using CH2Cl2-MeOH (10:1) to get 4a (6.4 g, 89.2%) as a yellow solid. 1H NMR (400 MHz, CDCl3) delta 7.94 (d, J = 9.0 Hz, 1H), 6.89 (d, J = 9.0 Hz, 1H), 3.88 (s, 3H), 3.36-3.39 (m, 4H), 2.60-2.63 (m, 4H), 2.50 (q, J = 7.2 Hz, 2H), 1.15 (t, J = 7.2 Hz, 3H). ESI-MS (m/z): [M + H]+ = 249.0.

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

Reference：
Article; Cui, Jing; Peng, Xia; Gao, Dingding; Dai, Yang; Ai, Jing; Li, Yingxia; Bioorganic and Medicinal Chemistry Letters; vol. 27; 16; (2017); p. 3782 – 3786;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

4318-42-7,4318-42-7, 1-Isopropylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Example lg: Synthesis of l-(4-methoxybenzyl)-7-(3-(4-isopropylpiperazin-l-yl)azetidin-l-yl)- l,5-naphthyridin-2(lH) -one (C-8) [00311] A mixture of l-(4-methoxybenzyl)-7-(3-oxoazetidin-l-yl)-l,5-naphthyridin-2(lH)-one (C-7) (5.796 g, 17.3 mmol, 1.0 eq) and 1 -isopropylpiperazine (4.432 g, 34.6 mmol, 2.0 eq) in DCM (150 mL) and acetic acid (0.5 mL) was heated at reflux temperature for 3 h, then NaBH(OAc)3 (7.33 g, 34.6 mmol, 2.0 eq) was added in portions and the resulting mixture was kept reflux overnight. The reactant mixture was cooled and diluted with H20 (300 mL) and extracted with DCM (4 x 100 mL). The combined organic layers were washed with brine, dried over Na2S04 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (2- 5percent MeOH-DCM) to afford the desired product l-(4-methoxybenzyl)-7-(3-(4-isopropylpiperazin-l- yl)azetidin-l-yl)-l,5-naphthyridin-2(lH)-one (C-8) (5.6 g, 72.3percent yield ) as a pale solid. lR NMR (300 MHz, CDC13- (5) delta: 7.83 (d, J = 7.5 Hz, 1H), 7.78 (s, 1H), 7.15 (d, J = 6.9 Hz, 2H), 6.85 (d, J = 6.6 Hz, 2H), 6.72 (d, J = 7.2 Hz, 1H), 6.37 (s, 1H), 5.40 (s, 2H), 4.02 (m, 2H), 3.78 (m, 5H), 3.67 (m, 1H), 3.51 (m, 1H), 3.42 (m, 1H), 2.97 (m,lH), 2.80 (m, 4H), 2.55 (m, 2H), 1.17 (d, J = 4.8 Hz, 6H); ESI-MS m/z : 448.3 [M+H]+.

As the paragraph descriping shows that 4318-42-7 is playing an increasingly important role.

Reference：
Patent; INTELLIKINE, LLC; REN, Pingda; LI, Liansheng; CHAN, Katrina; WO2013/78441; (2013); 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.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