Heterocyclic Building Blocks-piperazine

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.57260-71-6,tert-Butyl piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

tert-Butyl 4-(4-formylphenyl)piperazinecarboxylate (Compound 28) 1-(t-Butoxycarbonyl)piperazine (1.86 g, 10 mmol), p-fluorobenzaldehyde 27 (1.24 g, 10 mmol), and K2CO3 (1.74 g, 11 mmol) in dry pyridine (10 mL) are stirred at reflux under a nitrogen atmosphere for 24 h. Most of the solvent is removed under vacuum and the residue is partitioned between EtOAc (150 mL) and water (100 mL). The aqueous layer is washed with EtOAc (2*50 mL) and the combined organic layers are sequentially washed with 3% aq. citric acid (2*100 mL), water (100 mL), brine (100 mL), and dried (MgSO4). The solvent is removed under vacuum and the residue washed with hexanes and dried under vacuum. The product can be used as such, or further purified by silica gel column chromatography (dichloromethane-MeOH gradient)., 57260-71-6

57260-71-6 tert-Butyl piperazine-1-carboxylate 143452, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; Gordeev, Mikhail F.; Patel, Dinesh V.; Barbachyn, Michael R.; Gage, James R.; US2003/13737; (2003); A1;,
Piperazine – Wikipedia
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With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.109384-27-2,1-Methylpiperazin-2-one hydrochloride,as a common compound, the synthetic route is as follows.

Reference Example 46] 1-Methylpiperazin-2-one [Show Image] An aqueous 1 N sodium hydroxide solution was added to a suspension of 1-methylpiperazin-2-one hydrochloride (19.6 g) of Reference Example 21-(3) in dichloromethane, and the resultant mixture was partitioned. Further, sodium chloride was added to the aqueous layer to saturate the layer, and then the aqueous layer was extracted with dichloromethane. The organic layers were combined and dried over anhydrous sodium sulfate. After separation by filtration, the solvent was evaporated under reduced pressure, and the title compound (5.90 g) was obtained as an oily product. ESI-MSm/z: 115(M+H)+., 109384-27-2

109384-27-2 1-Methylpiperazin-2-one hydrochloride 17060766, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; DAIICHI PHARMACEUTICAL CO., LTD.; EP1785418; (2007); 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.5625-67-2,Piperazin-2-one,as a common compound, the synthetic route is as follows.

Step 1tert-butyl 4-benzyl-3-oxopiperazine-1-carboxylateDi-tert-butyl dicarbonate (750 mg, 3.44 mmol) was added to a solution of piperazine-2-one (344 mg, 3.44 mmol) in CH2C12 (13 mL). The solution was stirred at room temperature for 16 hours, then concentrated under vacuum. The residue was dissolved in N,Ndimethylformamide (10 mL) and stirred under nitrogen as sodium hydride (60% dispersion in oil, 0.25 g, 6.25 mmol) was added at room temperature. The mixture was stirred for 30 minutes, then benzyl bromide (0.532 mL, 4.47 mmol) was added. The mixture was stirred under nitrogen for 1 hour, and the reaction was quenched by cautious addition of water (3 mL). Finally, the mixture was diluted with water (50 mL) and stirred at room temperature for 2 hours. The resulting precipitate was collected by filtration and washed with water (40 mL), then dried under vacuum to the titled compound (0.82 g, 82%). ?H NMR (400 MHz, methanol-d4) ppm 1.46 (s, 9H), 3.30 – 3.33 (m, 2H), 3.60 (t, J = 5.2 Hz, 2H), 4.11 (s, 2H), 4.62 (s, 2H), 7.25 – 7.37 (m, 5H); MS (ESI) m/z 291 (M+H)., 5625-67-2

As the paragraph descriping shows that 5625-67-2 is playing an increasingly important role.

Reference：
Patent; ABBVIE INC.; SCANIO, Marc; BUNNELLE, William; KOENIG, John Robert; DRIZIN, Irene; PLIUSHCHEV, Marina; COWART, Marlon; WO2015/112445; (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.169447-70-5,(S)-tert-Butyl 2-methylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

169447-70-5, Step 1: (S)-tert-butyl 4-(4-fluorophenyl)-2-methylpiperazine-1-carboxylate A solution of (S)-tert-butyl 2-methylpiperazine-1-carboxylate (1.2 g, 6 mmol), 1-bromo-4-fluorobenzene (1.26 g, 7.2 mmol), t-BuONa (865 mg, 9 mmol), BINAP (150 mg, 0.24 mmol), Pd2 (dba)3 (110 mg, 0.12 mmol) in dry toluene (40 mL) was stirred under N2 at 80 C. for 16 hrs. The reaction mixture was concentrated and the residue was purified by chromatography (silica, EtOAc/PE=1/10) to afford (S)-tert-butyl-4-(4-fluorophenyl)-2-methylpiperazine-1-carboxylate (1.5 g, 5.1 mmol, 85%) as a yellow oil. ESI-MS (EI+, m/z): 295.1 [M+H]+.

As the paragraph descriping shows that 169447-70-5 is playing an increasingly important role.

Reference：
Patent; Navitor Pharmaceuticals, Inc.; O’Neill, David John; Saiah, Eddine; Kang, Seong Woo Anthony; Brearley, Andrew; Bentley, Jonathan; (136 pag.)US2019/389843; (2019); A1;,
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With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.414910-15-9,tert-Butyl 4-(cyclopropanecarbonyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

To a stirred mixture of compound tert-butyl 4-(cyclopropanecarbonyl)piperazine-1-carboxylate (3.7 g, 14.5 mmol) in methanol (15 mL) was added hydrochloride/methanol (15 mL, 3M)) at 0 C. After the addition, the mixture was allowed to stir at room temperature overnight. The mixture was concentrated to give cyclopropyl(piperazin-1-yl)methanone hydrochloride (2.74 g, yield 100%) as an off-white solid. 1H-NMR (400 MHz, DMSO-d6) delta (ppm): 0.71-0.76 (m, 4H), 1.96-2.03 (m, 1H), 3.04-3.16 (m, 4H), 3.69-4.08 (m, 4H), 9.58 (s, 2H); LC-MS (ESI) m/z: 155(M+1)+

414910-15-9, As the paragraph descriping shows that 414910-15-9 is playing an increasingly important role.

Reference：
Patent; LEAD THERAPEUTICS, INC.; US2010/35883; (2010); 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.278788-66-2,(R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

To a solution of imidazole (15.7 g, 231 mmol) in DCM (100 mL) was added SOCl 2 (8.25 g, 69.4 mmol, 5.03 mL) at 0° C. The reaction mixture was stirred at 15° C. for 1 hour. To the mixture was added tert-butyl (3R)-3-(hydroxymethyl)piperazine-1-carboxylate (5 g, 23.1 mmol) in DCM (100 mL) at -70° C. The reaction mixture was stirred at 15° C. for 12 hour. Upon completion, the reaction mixture was quenched by saturated NH 4Cl (100 mL) and separated, the aqueous layer was extracted with DCM (40 mL). The combined organic layers were washed with brine (20 mL), dried over Na 2SO 4, filtered and concentrated under vacuum to give tert-butyl (3aR)-1-oxo-3a,4,6,7-tetrahydro-3H-oxathiazolo[3,4-a]pyrazine-5-carboxyla- te (5.8 g, 22.1 mmol, 95.6% yield) as a brown solid., 278788-66-2

As the paragraph descriping shows that 278788-66-2 is playing an increasingly important role.

Reference：
Patent; Mirati Therapeutics, Inc.; Array BioPharma Inc.; Blake, James F.; Burgess, Laurence E.; Chicarelli, Mark Joseph; Christensen, James Gail; Cook, Adam; Fell, Jay Bradford; Fischer, John P.; Marx, Matthew Arnold; Mejia, Macedonio J.; Savechenkov, Pavel; Vigers, Guy P.A.; Smith, Christopher Ronald; Rodriguez, Martha E.; US2019/144444; (2019); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

1152367-80-0, (S)-1,3-Dimethylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Into a 40 mL sealed tube were added (3S) -1, 3-dimethylpiperazine (607.89 mg, 5.323 nMol, 1.3 equiv) , 6-fluoropyridine-2-carbonitrile (500 mg, 4.095 nMol, 1 equiv) , K 2CO 3 (1131.89 mg, 8.190 nMol, 2 equiv) and DMF (10 mL) at room temperature. The resulting mixture was stirred for 3 hours at 50. The reaction was quenched by the addition of sat. NaCl (aq. ) (250 mL) at room temperature. The resulting mixture was extracted with EtOAc (2 x 125 mL) . The combined organic layers were washed with sat. NaCl (aq. ) (250 mL) , dried over anhydrous Na 2SO 4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by Prep-TLC (CH 2Cl 2 /MeOH 30: 1) to afford 6- [ (2S) -2, 4-dimethylpiperazin-1-yl] pyridine-2-carbonitrile (280 mg, 31.61%) as a colorless oil. LCMS: m/z (ESI) , [M+H] + = 217.3

1152367-80-0, 1152367-80-0 (S)-1,3-Dimethylpiperazine 13152036, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; DIZAL (JIANGSU) PHARMACEUTICAL CO., LTD.; QI, Changhe; TSUI, Honchung; ZENG, Qingbei; YANG, Zhenfan; ZHANG, Xiaolin; (399 pag.)WO2020/35052; (2020); 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.78551-60-7,tert-Butyl 4-benzyl-3-oxopiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.,78551-60-7

To a solution of oxalyl chloride (214 mg, 1.65 mmol) in CH2CI2 (2.5 ml) in a dryice-acetone bath was added DMSO (356 mg, 4.56 mmol). After 5 min, a solution ofthe product of Step 7 (508 mg, 1.41 mmol) in CH2CI2 (3.5 ml) was added and themixture was stirred for 1 h. Triethylamine (700 nl, 5.02 mmol) was added and themixture was stirred for 15 min. The mixture was warmed to RT and stirred for 15 min.Water (30 ml) and CH2CI2 (40 ml) were added and the aqueous layer was extractedwith CH2CI2 (30 ml). The combined organic layer was washed with brine (50 ml),dried (MgSO/O, and concentrated to give the aldehyde, which was not further purified.To a solution of diisopropylamine (188 mg, 1.86 mmol) in THF (2.5 ml) in a dryice-acetone bath was added 1.6 M butyllithium in hexanes (1.40 ml, 2.24 mmol).After 5 min the mixture was put in an ice-water bath and stirred for 20 min. Thesolution was cooled in the dry ice-acetone bath again and a solution of the product ofPreparative Example 1, Step 5 (460 mg, 1.59 mmol) in THF (4 ml) was added. Themixture was stirred for 1 h. A solution of the above aldehyde in THF (4 ml) wasadded and the mixture was stirred for 1.5 h. The reaction was quenched with water(40 ml) and extracted with ether (50 ml). The aqueous layer was extracted with ether(3×40 ml). The combined organic layer was washed with brine (50 ml), dried(MgSO4), concentrated, and purified by PTLC (40% EtOAc/Hexanes) to give: fraction1 (137 mg, 15%). MS m/e 648 (M+H)+; fraction 2 (148 mg, 16%). MS m/e 648 (M+H)+

78551-60-7 tert-Butyl 4-benzyl-3-oxopiperazine-1-carboxylate 10891590, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; SCHERING CORPORATION; WO2006/14762; (2006); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

262368-30-9, N-(4-Aminophenyl)-N-methyl-2-(4-methylpiperazin-1-yl)acetamide is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

General procedure: To a suspension of methyl (Z)-1-acetyl-3-(ethoxy(phenyl)methylene)-2-oxoindoline-6-carboxylate (6) (500 mg,1.368 mmol) in DMF (3.5 mL) was added N-(4-aminophenyl)-N-methyl-2-(4-methylpiperazin-1-yl)acetamide (14) (395 mg,1.505 mmol, 1.1 equiv.) at RT. After heating the reaction mixture at 80 C for 1 h, it was allowed to cool to RT. Piperidine (297 lL,3.010 mmol, 2.2 equiv.) was then added and stirred for 2 h. Volatiles were removed in vacuo and water was added to the obtained residue and stirred for 15 min. The precipitate was then filtered under suction and cake was washed with water, then with minimum amount of cold methanol, and then ether. The obtained product was purified by column chromatography (neutral Al2O3,0-10% methanol in CH2Cl2) to afford 532 mg (72%) of target molecule 15.

262368-30-9, As the paragraph descriping shows that 262368-30-9 is playing an increasingly important role.

Reference：
Article; Edupuganti, Ramakrishna; Taliaferro, Juliana M.; Wang, Qiantao; Xie, Xuemei; Cho, Eun Jeong; Vidhu, Fnu; Ren, Pengyu; Anslyn, Eric V.; Bartholomeusz, Chandra; Dalby, Kevin N.; Bioorganic and Medicinal Chemistry; vol. 25; 9; (2017); p. 2609 – 2616;,
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.13889-98-0,1-Acetylpiperazine,as a common compound, the synthetic route is as follows.

General procedure: To a solution of substituted piperazines (0.9819mmol) in dry DMF (4mL), triethylamine (0.27mL, 1.9638mmol) and potassium iodide (16.29mg, 0.0981mmol) were added at RT under N2 atmosphere. Compound 2 (0.4g, 0.9819mmol) was added to the above reaction mixture and resultant mixture was heated at 125C. After the reaction was complete, as indicated by TLC, DMF was evaporated in vacuo. The obtained residue was diluted with 20mL of water. The compound was extracted with CH2Cl2 (3×5mL). The organic layers were collected, washed with saturated brine solution, dried over anhydrous MgSO4 and concentrated in vacuo. The resultant crude was purified by column chromatography [CH2Cl2/MeOH (1-10%)] to get the title compounds.

13889-98-0, 13889-98-0 1-Acetylpiperazine 83795, apiperazines compound, is more and more widely used in various fields.

Reference：
Article; Suresh, Narva; Nagesh, Hunsur Nagendra; Renuka, Janupally; Rajput, Vikrant; Sharma, Rashmi; Khan, Inshad Ali; Kondapalli Venkata Gowri, Chandra Sekhar; European Journal of Medicinal Chemistry; vol. 71; (2014); p. 324 – 332;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics