Category: 109384-27-2

Wang, Ning-Yu published the artcileDesign, synthesis and structure-activity relationship study of piperazinone-containing thieno[3,2-d]pyrimidine derivatives as new PI3Kδ inhibitors, Application In Synthesis of 109384-27-2, the main research area is thienopyrimidine piperazinone preparation SAR non Hodgkin lymphoma PI3K antiproliferative; Antiproliferative activity; PI3Kδ; Piperazinone; SAR; Thieno[3,2-d]pyrimidine.

Two classes of piperazinone-containing thieno[3,2-d]pyrimidines were designed and synthesized as new PI3Kδ inhibitors in this study. Detailed SAR study with respect to the piperazinone substituents at the 6-position of thieno[3,2-d]pyrimidine core demonstrated that piperazinone-containing thieno[3,2-d]pyrimidines would be more potent and selective for PI3Kδ than their piperazine counterparts, which led to the discovery of several potent PI3Kδ inhibitors with comparable or better antiproliferative activity against a panel of non-Hodgkin lymphoma (NHL) cell lines as compared with idelalisib. Our study will promote the development of new PI3Kδ inhibitors based on piperazinone-containing thieno[3,2-d]pyrimidine scaffold.

Bioorganic & Medicinal Chemistry Letters published new progress about Antiproliferative agents. 109384-27-2 belongs to class piperazines, name is 1-Methylpiperazin-2-one hydrochloride, and the molecular formula is C5H11ClN2O, Application In Synthesis of 109384-27-2.

Referemce:
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.109384-27-2,1-Methylpiperazin-2-one hydrochloride,as a common compound, the synthetic route is as follows.

To a solution of 4-(3-(4-cyanophenyl)imidazo[l ,2-b]pyridazin-6-yl)benzoic acid (50 mg, 0.147 mmol) in DMF (0.74 mL) were added HATU (84 mg, 0.221 mmol), N-methyl morpholine (65 mu, 0.588 mmol) and l-methyl-2-oxopiperazine hydrochloride (27 mg, 0.177 mmol). The reaction mixture was stirred at room temperature under inert atmosphere for 18 h, then was diluted with water (15 mL) and extracted with EtOAc (3×30 mL). The combined organic layer was dried over Na2S04, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, eluent CHCl3/MeOH 92:8), followed by preparative HPLC (CI 8, eluent ACN, water, formic acid 0.1%) to afford 4-(6-(4- (4-methyl-3 -oxopiperazine- 1 -carbonyl)phenyl)imidazo[ 1 ,2-b]pyridazin-3 -yl)benzonitrile (16 mg, 24%, AUC HPLC 99%) as a yellow solid. 1H NMR (400 MHz, DMSO-i delta 8.52-8.47 (m, 3H), 8.39 (d, J= 9.6 Hz, 1H), 8.23 (d, J= 8.4 Hz, 2H), 8.04-7.97 (m, 3H), 7.67 (d, J = 8.4 Hz, 2H), 4.25-3.95 (m, 2H), 3.95-3.75 (m, lH), 3.75-3.55 (m, 1H), 3.50-3.20 (m, 2H), 2.88 (s, 3H); MS (ESI) m/z 437 [C25H2oN602 + H] +.

109384-27-2, As the paragraph descriping shows that 109384-27-2 is playing an increasingly important role.

Reference：
Patent; AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH; NACRO, Kassoum; DURAISWAMY, Athisayamani, Jeyaraj; CHENNAMANENI, Lohitha, Rao; WO2013/147711; (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.109384-27-2,1-Methylpiperazin-2-one hydrochloride,as a common compound, the synthetic route is as follows.

To a solution of 4-(3-(4-cyanophenyl)imidazo[l ,2-b]pyridazin-6-yl)benzoic acid (50 mg, 0.147 mmol) in DMF (0.74 mL) were added HATU (84 mg, 0.221 mmol), N-methyl morpholine (65 mu, 0.588 mmol) and l-methyl-2-oxopiperazine hydrochloride (27 mg, 0.177 mmol). The reaction mixture was stirred at room temperature under inert atmosphere for 18 h, then was diluted with water (15 mL) and extracted with EtOAc (3×30 mL). The combined organic layer was dried over Na2S04, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, eluent CHCl3/MeOH 92:8), followed by preparative HPLC (CI 8, eluent ACN, water, formic acid 0.1%) to afford 4-(6-(4- (4-methyl-3 -oxopiperazine- 1 -carbonyl)phenyl)imidazo[ 1 ,2-b]pyridazin-3 -yl)benzonitrile (16 mg, 24%, AUC HPLC 99%) as a yellow solid. 1H NMR (400 MHz, DMSO-i delta 8.52-8.47 (m, 3H), 8.39 (d, J= 9.6 Hz, 1H), 8.23 (d, J= 8.4 Hz, 2H), 8.04-7.97 (m, 3H), 7.67 (d, J = 8.4 Hz, 2H), 4.25-3.95 (m, 2H), 3.95-3.75 (m, lH), 3.75-3.55 (m, 1H), 3.50-3.20 (m, 2H), 2.88 (s, 3H); MS (ESI) m/z 437 [C25H2oN602 + H] +.

109384-27-2, As the paragraph descriping shows that 109384-27-2 is playing an increasingly important role.

Reference：
Patent; AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH; NACRO, Kassoum; DURAISWAMY, Athisayamani, Jeyaraj; CHENNAMANENI, Lohitha, Rao; WO2013/147711; (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.109384-27-2,1-Methylpiperazin-2-one hydrochloride,as a common compound, the synthetic route is as follows.

[0348] Methyl-2-piperazinone hydrochloride (1:1) (300 mg, 1.99 mmol) was combined with dichloromethane (20 mL) to give a light yellow suspension. N,N-Diisopropylethylamine (309 mg, 417 mul, 2.39 mmol) was added at 0 C. Subsequently 3-(4-cyanophenyl)-2-oxaziridinecarboxylic acid 1,1-dimethylethyl ester (441 mg, 1.79 mmol) in dichloromethane (10 mL) was added during 35 min at 0 C. and the reaction mixture was stirred for 1 h at 0 C. Afterwards the reaction mixture was concentrated in vacuo and the residue was purified by flash chromatography (silica gel, 20 g, 0% to 100% ethyl acetate in n-heptane) to deliver an oil contaminated with 4-cyano-benzaldehyde. This material was purified by a second chromatography (aminophase 5 g, ethyl acetate/n-heptane 1/1) to give the title compound (67 mg, 15%) as white solid; GC-MS (EI) 229.0 (M)+

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; Grether, Uwe; Hebeisen, Paul; Mohr, Peter; Ricklin, Fabienne; Roever, Stephan; US2013/65876; (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.109384-27-2,1-Methylpiperazin-2-one hydrochloride,as a common compound, the synthetic route is as follows.

[0348] Methyl-2-piperazinone hydrochloride (1:1) (300 mg, 1.99 mmol) was combined with dichloromethane (20 mL) to give a light yellow suspension. N,N-Diisopropylethylamine (309 mg, 417 mul, 2.39 mmol) was added at 0 C. Subsequently 3-(4-cyanophenyl)-2-oxaziridinecarboxylic acid 1,1-dimethylethyl ester (441 mg, 1.79 mmol) in dichloromethane (10 mL) was added during 35 min at 0 C. and the reaction mixture was stirred for 1 h at 0 C. Afterwards the reaction mixture was concentrated in vacuo and the residue was purified by flash chromatography (silica gel, 20 g, 0% to 100% ethyl acetate in n-heptane) to deliver an oil contaminated with 4-cyano-benzaldehyde. This material was purified by a second chromatography (aminophase 5 g, ethyl acetate/n-heptane 1/1) to give the title compound (67 mg, 15%) as white solid; GC-MS (EI) 229.0 (M)+

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; Grether, Uwe; Hebeisen, Paul; Mohr, Peter; Ricklin, Fabienne; Roever, Stephan; US2013/65876; (2013); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

109384-27-2, 1-Methylpiperazin-2-one hydrochloride is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Example 51A 6-chloro-2-methyl-5-(4-methyl-3-oxopiperazin-1-yl)pyridazin-3(2H)-one [0791] A mixture of Example 18B (0.179 g, 1.0 mmol), 1-methylpiperazin-2-one, hydrochloric acid (0.301 g, 2 mmol), and triethylamine (0.405 g 4.0 mmol) in ethanol (10 mL) was heated under reflux for 16 hours. The solvent was removed, and the residue was purified by flash column chromatography on silica gel eluting with 1-5% methanol in ethyl acetate to afford 0.21 g (82%) of the title compound.

109384-27-2, As the paragraph descriping shows that 109384-27-2 is playing an increasingly important role.

Reference：
Patent; HUBBARD, Robert D.; WANG, Le; PARK, Chang H.; SUN, Chaohong; McDANIEL, Keith F.; PRATT, John K.; SOLTWEDEL, Todd N.; WENDT, Michael D.; HOLMS, John H.; LIU, Dachun; SHEPPARD, George S.; US2013/331382; (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.109384-27-2,1-Methylpiperazin-2-one hydrochloride,as a common compound, the synthetic route is as follows.

(rac)-6-chloro-3-(1 -(4,6-difluoro-1 -isopropyl-1 H-indazol-5-yl)ethyl)imidazo[1 ,2-b]pyridazine (Intermediate U, 56.4 mg, 0.15 mmol), KF (43.6 mg, 0.75 mmol) and 1-methylperazine-2- one hydrochloride (51.4 mg, 0.45 mmol) were suspended in NMP (0.4 ml_). The RM was stirred at 180 0C for 4 h. The mixture was diluted with EtOAc and washed with NaHCO3 10% (2 x) and water (4 x). The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography and afforded the title compound as a light brown foam (tR 4.06 min (conditions 5), MH+ = 454.3, 1H-NMR in DMS0-d6: 8.09 (s, 1 H); 7.81 (d, 1 H); 7.53 (s, 1 H); 7.43 (d, 1H); 7.05 (d, 1 H), 4.86 (m, 2H); 4.03 (d, 1H); 3.81 (d, 1H); 3.64 (m, 2H); 3.24 (m, 2H); 2.80 (s, 3H); 1.79 (d, 3H), 1.41 (m, 6H)).

109384-27-2, The synthetic route of 109384-27-2 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; NOVARTIS AG; FURET, Pascal; McCARTHY, Clive; SCHOEPFER, Joseph; STUTZ, Stefan; WO2011/15652; (2011); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

109384-27-2, 1-Methylpiperazin-2-one hydrochloride is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Example 51A 6-chloro-2-methyl-5-(4-methyl-3-oxopiperazin-1-yl)pyridazin-3(2H)-one [0791] A mixture of Example 18B (0.179 g, 1.0 mmol), 1-methylpiperazin-2-one, hydrochloric acid (0.301 g, 2 mmol), and triethylamine (0.405 g 4.0 mmol) in ethanol (10 mL) was heated under reflux for 16 hours. The solvent was removed, and the residue was purified by flash column chromatography on silica gel eluting with 1-5% methanol in ethyl acetate to afford 0.21 g (82%) of the title compound.

109384-27-2, As the paragraph descriping shows that 109384-27-2 is playing an increasingly important role.

Reference：
Patent; HUBBARD, Robert D.; WANG, Le; PARK, Chang H.; SUN, Chaohong; McDANIEL, Keith F.; PRATT, John K.; SOLTWEDEL, Todd N.; WENDT, Michael D.; HOLMS, John H.; LIU, Dachun; SHEPPARD, George S.; US2013/331382; (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.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.109384-27-2,1-Methylpiperazin-2-one hydrochloride,as a common compound, the synthetic route is as follows.

Step AF.1 : 4-[3-(4-Chloro-5-iodo-pyrrolo[2,3-d]pyrimidin-7-yl)-cyclobutylmethy.]-1-methyl- piperazin-2-oneMethylpiperazin-2-one HCI salt (290 mg, 1.2832 mmol), 3-(4-Chloro-5-iodo-pyrrolo[2,3- d]pyrimidin-7-yl)-cyclobutanecarbaldehyde (Step AF.2, 265 mg, 0.733 mmol), and DIPEA (1.306 mL, 7.33 mmol) were dissolved in 1,2-dichloroethane (32 mL) and stirred at RT for 45 min. After adding NaBH(OAc)3 (409 mg, 1.832 mmol) the reaction mixture was stirred for 35 min at RT. Then, concentrated NaHC03 solution (50 mL) was added and the reaction mixture was extracted with DCM ( 40 mL, 4 x). The combined organic phases were washed with brine (10 mL), dried (Na2S04), and the solvent was evaporated, the resulting residue was purified by means of a Sepacore Control chromatographer (Buchi, Flawil, Switzerland) using RediSept silica gel column (12 g) (30 mL min; DCM: 10 min, DCM -> DCM/MeOH/NH3(99.45:0.5 :05) in 30 min) yielding the title compound as white solid. HPLC (Method B) tRel = 1.724 min. HPLC/MS tR = 0.52 min, M+H = 441.1. 1H NMR (600 MHz, DMSO-d6) delta ppm 8.16 (s, 1H), 7.74 (s, 1H), 6.15 (s/b, 2H), 5.00 (quintet, 1H), 3.26 (t, 2H), 2.95 (s, 2H), 2.78 (s, 3H), 2.65 (t, 2H), 2.56 (t, 2H), 2.50/2.15 (m/m, 2H/2H), 2.29 (m, 1H).

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; NOVARTIS AG; IRM LLC, a Delaware Limited Liability Company; CHEN, Bei; FAIRHURST, Robin, Alec; FLOERSHEIMER, Andreas; FURET, Pascal; JIANG, Songchun; LU, Wenshuo; MARSILJE, Thomas, H.; VAUPEL, Andrea; WO2011/64211; (2011); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics