Heterocyclic Building Blocks-piperazine

109-01-3, 1-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

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.

109-01-3, 109-01-3 1-Methylpiperazine 53167, apiperazines compound, is more and more widely used in various fields.

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
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59878-57-8,59878-57-8, 1-(Cyclopropylcarbonyl)piperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

General procedure: 74 (250 mg, 0.71 mmol) was mixed with acetonitrile (5 mL), diisopropylethylamine (3 mL) and KI (250 mg) and 2,2-dimethyl-1-(piperazin-1-yl)propan-1-one (600 mg) and heated at 80 C for 12 h. On cooling, the mixture was poured into a saturated solution of ammonium chloride (40 mL) and extracted with ethyl acetate (3 x 20 mL). The organic phases were combined, washed with brine (40 mL), dried (magnesium sulfate), filtered and concentrated. The crude residue was purified by Flashmaster II (eluting with 0-50 % ethyl acetate in dichloromethane) to give 1-(4-{[2-fluoro-4-(trifluoromethyl)phenyl](pyridin-3-yl)methyl}piperazin-1-yl)-2,2-dimethylpropan-1-one (14) (52 mg, 17 %) as a yellow oil.

59878-57-8 1-(Cyclopropylcarbonyl)piperazine 2064235, apiperazines compound, is more and more widely used in various fields.

Reference：
Article; Keenan, Martine; Alexander, Paul W.; Diao, Hugo; Best, Wayne M.; Khong, Andrea; Kerfoot, Maria; Thompson, R. C. Andrew; White, Karen L.; Shackleford, David M.; Ryan, Eileen; Gregg, Alison D.; Charman, Susan A.; Von Geldern, Thomas W.; Scandale, Ivan; Chatelain, Eric; Bioorganic and Medicinal Chemistry; vol. 21; 7; (2013); p. 1756 – 1763;,
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.109-01-3,1-Methylpiperazine,as a common compound, the synthetic route is as follows.

Example 1 Preparation of 4-[(4-methyl-1-piperazinyl)methyl]benzoic acid (formula (2)) 350 ml of ethanol was added to 155 g (1.547 mol) of N-methylpiperazine. At room temperature (25 ± 3C), 60 g (0.351 mol) of 4-chloromethylbenzoic acid was added thereto and stirred for 6-7 hours. The reaction was analyzed by HPLC, and then the reaction solution was distilled under reduced pressure to remove ethanol, and 60 ml of 1-butanol was added thereto. The mixture was azeotropically distilled at 70 ± 2C and concentrated to produce a solid. 600 ml of 2-propanol was added thereto and the mixture was stirred at room temperature (25 ± 3C) for 30 minutes, stirred under reflux for 15 minutes, and then stirred at room temperature (25 ± 3C) for 12 hours with slow cooling. The produced precipitate was cooled to 19 ± 3C, stirred for 1 hour and then filtered. The filtrate was washed with 50 ml of cooled 2-propanol and dried in an oven at 60C, thereby obtaining a white compound of formula (2) (60 g, yield: 72%, purity: 95% or higher). HPLC purity: 99.123% (desmethyl impurity: 0.042%, starting material 0.42%).

109-01-3, The synthetic route of 109-01-3 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Bcworld Pharm. Co. Ltd.; EP2530077; (2012); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

112984-60-8, 6-Fluoro-1-methyl-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Synthesis of 7-{4-[l~Chlowmethyi-2-(2-methyl-5-niiro mid zol-l-yl)- ethoxycarbonylmeihyl J-piperazin-1 -yl }-6~fl uoro- 1 ~methyl~4~oxo-4H~2~thia-8b~ aza-cyclobuia[a]naphthalene~3-carboxylic acid (1): To a stirred solution of 6- Fluoro- 1 -methy l-4-oxo-7-piperazin- 1 -y l~4H-2-thia~8b-aza~ cyclobuta[a]naphthalene-3-carboxylic acid, (III) (0.07 Ig, 0.2 mmol) in dimethylformamide (10ml) was added potassium carbonate (0.04g, 0.3 mmol) followed by addition of compound (II) (O.lg, 0.3 mmol) and the reaction mixture was stirred at RT for 3h. The reaction mixture was diluted with ethylacetate, washed two times with water and finally dried over sodium sulphate to obtain the crude mass. The crude was purified by flash column chromatography while eluting with 3-5% methanol/dichloromethane mixture to obtain the pure compound (1), i.e., Compound 90 from Table 1, with 30% isolated yield. H-NMR (400 MHz, DMSO) 6ppm: 2.19 (3H, d, J = 6.4 Hz, CH3), 2.57 (3H, s, CH3), 2.7 (4H, m, 2 x CH2), 3.1-3.3 (2H, s, COCH2), 3.32 (4H, m, 2 x CH2), 3.77-3.90(2H, ddd, Jx = 3.6 Hz, J2 = 12.4 Hz, J3 = 35.2 Hz, CH2C1), 4.40- 4.56 (1H, dd, Ji = 9.6 Hz, J2 = 14 Hz CHN), 4.76 (1H, d, J = 14 Hz, CHN), 5.44 (1H, d , J-5.6Hz CHOCO), 6.0-6.1 1 (1H, q, Jx = 6 Hz, J2 = 12.4 Hz, CHSN), , 6.4 (1H, d, Jx = 6.8 Hz Ar-H), 7.8 (1H, d, J = 14 Hz, Ar-H), 8.04 (1H, s, Ar-H). ESI-MS (m/z): 609 (M+H)+.

112984-60-8, As the paragraph descriping shows that 112984-60-8 is playing an increasingly important role.

Reference：
Patent; VYOME BIOSCIENCES PVT. LTD.; SENGUPTA, Shiladitya; CHAWRAI, Suresh Rameshlal; GHOSH, Shamik; GHOSH, Sumana; JAIN, Nilu; SADHASIVAM, Suresh; BUCHTA, Richard; BHATTACHARYYA, Anamika; WO2015/114666; (2015); A2;,
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With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.5747-48-8,11-(Piperazin-1-yl)dibenzo[b,f][1,4]thiazepine,as a common compound, the synthetic route is as follows.

Example 1: l-(4-Dibenzo[b,f| [l,4]thiazepin-ll-yl-piperazin-l-yl)-2-methyl-propan-l-oneAn ice-bath-cooled solution of 1 l-iperazin-l-yldibenzo[b,f][l,4]thiazepine (“PDBTZ”, 1 mmol) and triethylamine (1.1 mmol) in dichloromethane (5 mL) is treated with 2-methylpropionic acid chloride (1.1 mmol). The mixture is warmed to ambient temperature and stirred for one hour. Water is added and the mixture is extracted with dichloromethane. The organic portion is washed (brine), dried (sodium sulfate), and evaporated. The crude material is purified by flash chromatography to provide the title compound., 5747-48-8

Big data shows that 5747-48-8 is playing an increasingly important role.

Reference：
Patent; ASTRAZENECA AB; WO2008/79838; (2008); A1;,
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Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.76003-29-7,1-Boc-3-Oxopiperazine,as a common compound, the synthetic route is as follows.

76003-29-7, To a solution of the product of Step 7 (10.0 g, 50.0 mmol) in anhydrous DMF(250 ml) in an ice-water bath were added sodium hydride (2.40 g, 60.0 mmol) andbenzyl chloride (6.60 g, 52.5 mmol). The mixture was stirred at RT for 4.5 h. Thereaction was quenched with water (10 ml), diluted with CH2CI2 (500 ml), and washedwith water (2x250ml). The organic layer was extracted with saturated NH4CI (200 ml),dried (MgSO4), concentrated, and purified by column chromatography (gradientMeOH/CH2CI2 0-5%) to give the product (10.7 g, 74%). 1H-NMR (CDCI3): 6=7.2-7.3(m, 5H), 4.57 (s, 2H), 4.10 (s, 2H), 3.53 (m, 2H), 3.19 (m, 2H), 1.41 (s, 9H).

As the paragraph descriping shows that 76003-29-7 is playing an increasingly important role.

Reference：
Patent; SCHERING CORPORATION; WO2006/14944; (2006); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

630125-91-6, 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,630125-91-6

Into a solution of 4-(4-Ethyl-piperazin-1-ylmethyl)-3-trifluoromethyl- phenylamine (3.0 g, 1.04 mmol, 1.0 eq. ) in dichloromethane (5.2 ml) was added diisopropylethyl amine,(2.00 ml, 1.14 mmol, 1.1 eq.). The solution was cooled to 0 C, after which 4-Methyl-3-nitrobenzoylchloride (2.13 g, 1.07 mmol, 1.03 eq. ) was added in portions into the reaction mixture which was further equilibrated for 30 minutes. The reaction mixture was then partitioned between dichloromethane and saturated sodium carbonate solution. The organic layer was separated and the aqueous layer was extracted with dichloromethane. The combined organic extracts were washed with water, brine, dried over Na2S04, filtered and concentrated to afford the desired product (4.58 g, 98%). The desired compound was used in the next step without further purification.

The synthetic route of 630125-91-6 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; IRM LLC; WO2005/123719; (2005); 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.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