Category: 5464-12-0

5464-12-0, 1-(2-Hydroxyethyl)-4-methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

5464-12-0, Compound 132 was synthesized according to the following production scheme.

The synthetic route of 5464-12-0 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; SBI BIOTECH CO., LTD.; CRYSTALGENOMICS, INC.; US2011/190299; (2011); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5464-12-0,5464-12-0, 1-(2-Hydroxyethyl)-4-methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

200 mg mixture of 4-chloro-5-[3,5-dichloro-2,6-dimethyl-4-[2-(4-methylpiperazin-l-yl) ethoxy]phenyl] -6-(4-fluorophenyl)thieno [2,3 – ]pyrimidine and 4-bromo-5 – [3 ,5 -dichloro- 2,6-dimethyl-4-[2-(4-methylpiperazin-l-yl)ethoxy]phenyl]-6-(4-fluorophenyl)thieno[2,3-(i] pyrimidine (0.33 mmol), 211 mg ethyl (2i?)-2-hydroxy-3-[2-[[2-(2-methoxyphenyl) pyrimidin-4-yl]methoxy]phenyl]propanoate (0.52 mmol) and 202 mg Cs2C03 (0.62 mmol) was dissolved in 5 mL tert-butanol and the mixture was stirred at 70 °C until no further conversion was observed. It was diluted with ethyl acetate and then it was washed with brine. The organic layer was dried over Na2S04, filtered and concentrated under reduced pressure and purified via flash chromatography using EtOAc and methanol as eluents to obtain ethyl (2i?)-2-[5-[3,5-dichloro-2,6-dimethyl-4-[2-(4-methylpiperazin-l-yl)ethoxy] phenyl] -6-(4-fluorophenyl)thieno [2,3 – ]pyrimidin-4-yl]oxy-3 – [2- [ [2-(2-methoxyphenyl) pyrimidin-4-yl]methoxy]phenyl]propanoate. The obtained intermediate was dissolved in 5 mL dioxane-water 1 : 1 (10 mL/mmol) and 145 mg LiOH x H20 (3.45 mmol) was added. The mixture was stirred at r.t. until no further conversion was observed. Then it was diluted with brine, neutralized with 2 M HC1, extracted with DCM, dried over Na2S04, filtered and concentrated under reduced pressure and purified via preparative reversed phase chromatography using 5 mM aqueous NH4HC03 solution and MeCN as eluents to obtain Preparation 13. 1H NMR (400 MHz, DMSO-d6): 8.89 (d, 1H), 8.60 (s, 1H), 7.81 (d, 1H), 7.53 (dd, 1H), 7.45 (td, 1H), 7.29-7.21 (m, 4H), 7.17-7.13 (m, 1H), 7.14 (d, 1H), 7.04 (td, 1H), 7.01 (d, 1H), 6.76 (t, 1H), 6.20 (d, 1H), 5.45 (dd, 1H), 5.26 (d, 1H), 5.20 (d, 1H), 4.06-4.01 (m, 2H), 3.76 (s, 3H), 3.46 (dd, 1H), 2.79-2.74 (m, 2H), 2.67-2.38 (m, 8H), 2.33 (s, 3H), 2.26 (s, 3H), 2.22 (dd, 1H), 1.73 (s, 3H) HRMS (M+2H)2+ = 462.1310

The synthetic route of 5464-12-0 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; LES LABORATOIRES SERVIER; VERNALIS (R&D) LIMITED; SZLAVIK, Zoltan; KOTSCHY, Andras; CHANRION, Maia; DEMARLES, Didier; GENESTE, Olivier; DAVIDSON, James Edward Paul; MURRAY, James Brooke; SIPOS, Szabolcs; PACZAL, Attila; BALINT, Balazs; (74 pag.)WO2016/207225; (2016); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5464-12-0, 1-(2-Hydroxyethyl)-4-methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,5464-12-0

General procedure: To a solution of triphenylphosphine (0.37 mmol) in THF (30 mL) was slowly added diisopropyl azodicarboxylate (0.37 mmol) in 15 min at 0 °C and the mixture was stirred for another 15 min. At the same temperature, to the resulting mixture was slowly added a solution of 20 (0.185 mmol) and corresponding alcohol (0.37 mmol) dissolved in 20 mL THF. The ice bar was removed and the reaction mixture was stirred at room temperature for 12 h. The reaction mixture was evaporated in vacuo, and the residue was purified by column chromatography to afford the product.

The synthetic route of 5464-12-0 has been constantly updated, and we look forward to future research findings.

Reference：
Article; Xing, Weiqiang; Ai, Jing; Jin, Shiyu; Shi, Zhangxing; Peng, Xia; Wang, Lang; Ji, Yinchun; Lu, Dong; Liu, Yang; Geng, Meiyu; Hu, Youhong; European Journal of Medicinal Chemistry; vol. 95; (2015); p. 302 – 312;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5464-12-0,5464-12-0, 1-(2-Hydroxyethyl)-4-methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

A solution of triphenylphosphane (31.7966 mg, 0.121 mmol) in 1 : 1 DCM:THF (0.6 mL) was cooled to 0°C and treated with diisopropyl azodicarboxylate (0.023 mL, 0.121 mmol) and stirred at 0°C for 15 min. The reaction mixture was treated with 6-hydroxy-4-(6-(4- (pyridin-2-yloxy)piperidin-l-yl)pyridin-3-yl)pyrazolo[l,5-a]pyridine-3-carbonitrile(Intermediate P78, 25.0 mg, 0.0606 mmol) in a 1 : 1 DCM:THF (0.6 mL) and 1-(N- hydroxyethyl)-4-methyl piperazine (13.1 mg, 0.0909 mmol). The reaction mixture was allowed to warm to rt and was stirred at this temperature for 30 min. The reaction mixture was concentrated in vacuo, and the resultant crude residue was directly purified by C-18 reverse phase chromatography (5-95percent ACN in water [+ 0.1percent TFA] as the gradient eluent). The fractions containing the desired product were diluted with 4: 1 DCMTPA and washed with saturated NaHC03(aq). The organic extract was dried over anhydrous Na2S04(S), filtered, and concentrated in vacuo to afford the title compound (31.5 mg, 0.0526 mmol, 86.8percent yield). MS (apci) m/z = 539.2 (M+H).

The synthetic route of 5464-12-0 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; ANDREWS, Steven W.; ARONOW, Sean; BLAKE, James F.; BRANDHUBER, Barbara J.; COLLIER, James; COOK, Adam; HAAS, Julia; JIANG, Yutong; KOLAKOWSKI, Gabrielle R.; MCFADDIN, Elizabeth A.; MCKENNEY, Megan L.; MCNULTY, Oren T.; METCALF, Andrew T.; MORENO, David A.; RAMANN, Ginelle A.; TANG, Tony P.; REN, Li; WALLS, Shane M.; (946 pag.)WO2018/71454; (2018); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5464-12-0,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.5464-12-0,1-(2-Hydroxyethyl)-4-methylpiperazine,as a common compound, the synthetic route is as follows.

A cold (0 °C) solution of PPh3 (32.6 mg, 0.124 mmol) in 1:1 DCM:THF (1.0 mL) was treated with DIAD (24.5 .iL, 0.124 mmol), and stirred for 15 mm at 0 °C. The resulting 0 °C mixture was treated with a solution of (4-(6-(4-benzylpiperazin- 1 -yl)pyridin-3 -yl)-6- hydroxypyrazolo[1,5-a]pyridine-3-carbonitrile (Example 1; 34.0 mg, 0.0828 mmol) and 1-(N- hydroxyethyl)-4-methyl piperazine (14.3 mg, 0.0994 mmol) in 1:1 DCM:THF (2.0 mL). The reaction mixture was stirred for 16 h at room temperature and then concentrated in vacuo. Purification of the crude residue by C18 reverse phase chromatography (5-95percent water-ACN with0.1percent TFA as the gradient eluent) cleanly provided the title compound as the TFA salt. The salt was converted to the free base by partitioning between 4:1 DCM:iPrOH and saturated NaHCO3(aq). The resulting organic extracts were combined, dried over anhydrous Na2SO4(), filtered and concentrated in vacuo to afford the title compound (20.1 mg, 45percent yield). MS (apci) m/z = 537.2 (M+H). ?H NMR (400 IVIHz, DMSO-P) : 8.70-8.69 (d, 1H), 8.57 (s, 1H), 8.32-8.3 1 (d, 1H), 7.78-7.75 (dd, 1H), 7.52 (s, 1H), 7.35-7.25 (m, 5H), 6.93-6.91 (d, 1H), 4.21-4.18 (t, 2H), 3.60-3.57 (m, 4H), 3.53 (s, 2H), 3.18-3.13 (q, 2H), 2.73-2.70 (t, 2H), 2.50-2.47 (m, 8H), 2.13 (s, 3H), 1.32- 1.28 (t, 2H).

The synthetic route of 5464-12-0 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; ANDREWS, Steven W.; ARONOW, Sean; BLAKE, James F.; BRANDHUBER, Barbara J.; COOK, Adam; HAAS, Julia; JIANG, Yutong; KOLAKOWSKI, Gabrielle R.; MCFADDIN, Elizabeth A.; MCKENNEY, Megan L.; MCNULTY, Oren T.; METCALF, Andrew T.; MORENO, David A.; TANG, Tony P.; REN, Li; (668 pag.)WO2018/71447; (2018); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5464-12-0,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.5464-12-0,1-(2-Hydroxyethyl)-4-methylpiperazine,as a common compound, the synthetic route is as follows.

A cold (0 °C) solution of PPh3 (32.6 mg, 0.124 mmol) in 1:1 DCM:THF (1.0 mL) was treated with DIAD (24.5 .iL, 0.124 mmol), and stirred for 15 mm at 0 °C. The resulting 0 °C mixture was treated with a solution of (4-(6-(4-benzylpiperazin- 1 -yl)pyridin-3 -yl)-6- hydroxypyrazolo[1,5-a]pyridine-3-carbonitrile (Example 1; 34.0 mg, 0.0828 mmol) and 1-(N- hydroxyethyl)-4-methyl piperazine (14.3 mg, 0.0994 mmol) in 1:1 DCM:THF (2.0 mL). The reaction mixture was stirred for 16 h at room temperature and then concentrated in vacuo. Purification of the crude residue by C18 reverse phase chromatography (5-95percent water-ACN with0.1percent TFA as the gradient eluent) cleanly provided the title compound as the TFA salt. The salt was converted to the free base by partitioning between 4:1 DCM:iPrOH and saturated NaHCO3(aq). The resulting organic extracts were combined, dried over anhydrous Na2SO4(), filtered and concentrated in vacuo to afford the title compound (20.1 mg, 45percent yield). MS (apci) m/z = 537.2 (M+H). ?H NMR (400 IVIHz, DMSO-P) : 8.70-8.69 (d, 1H), 8.57 (s, 1H), 8.32-8.3 1 (d, 1H), 7.78-7.75 (dd, 1H), 7.52 (s, 1H), 7.35-7.25 (m, 5H), 6.93-6.91 (d, 1H), 4.21-4.18 (t, 2H), 3.60-3.57 (m, 4H), 3.53 (s, 2H), 3.18-3.13 (q, 2H), 2.73-2.70 (t, 2H), 2.50-2.47 (m, 8H), 2.13 (s, 3H), 1.32- 1.28 (t, 2H).

The synthetic route of 5464-12-0 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; ANDREWS, Steven W.; ARONOW, Sean; BLAKE, James F.; BRANDHUBER, Barbara J.; COOK, Adam; HAAS, Julia; JIANG, Yutong; KOLAKOWSKI, Gabrielle R.; MCFADDIN, Elizabeth A.; MCKENNEY, Megan L.; MCNULTY, Oren T.; METCALF, Andrew T.; MORENO, David A.; TANG, Tony P.; REN, Li; (668 pag.)WO2018/71447; (2018); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5464-12-0,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.5464-12-0,1-(2-Hydroxyethyl)-4-methylpiperazine,as a common compound, the synthetic route is as follows.

A 250 ml three-necked flask equipped with a thermometer, a condenser, a bubble counter and a dropping funnel, and with magnetic stirring, is charged with 60 ml of THF and 7.9 g (50.94 mmol) of 2-(4-methylpiperazin-1 -yl)ethanol. The solution obtained is cooled to zero degrees and 2.04 g (50.94 mmol) of sodium hydride are gently added at this temperature. Stirring is continued at zero degrees for 1 hour. A solution of 7.9 g (42.45 mmol) of 1 -fluoro-2,4-dinitrobenzene and of 70 ml of THF, cooled beforehand to zero degrees, is then added dropwise to the previous medium. The reaction is monitored by TLC, elution being carried out with MeOH/CH2CI2. After stirring overnight at ambient temperature, the solvent is eliminated by evaporation under vacuum until a brown-yellow solid is obtained which, via purification by silica column flash chromatography (CH2Cl2/MeOH) gives, after evaporation of the solvent, a brown solid with a mass of 8.39 g (63.7percent yield) corresponding to the expected compound.

The synthetic route of 5464-12-0 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; L’OREAL; FADLI, Aziz; WO2014/26952; (2014); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5464-12-0, 1-(2-Hydroxyethyl)-4-methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,5464-12-0

Sodium hydride (60percent in mineral oil; 43.56 g; 1089 mmol) was added to a 3L reaction flask under nitrogen. A mechanical stirrer and thermocouple was attached. Dry diglyme (400 mL) was added. A solution of 2-(4-methylpiperazin-l-yl)ethanol (157 g; 1089 mmol) in diglyme (450 mL) was added slowly with stirring. The mixture was stirred with warming to 40 °C for 1 hour. 4-Chloropyridin-2-amine (70.0 g; 544.5 mmol) was added as a solid. The mixture was heated to 80 °C with stirring until effervescence had ceased. The temperature was increased to 157 °C for 16 hours. The mixture was allowed to cool and diluted with water (500 mL). THF (1000 mL) was added followed by sodium chloride (sufficient to saturate the aqueous phase). The phases were separated and the aqueous phase was further extracted with THF (3 x 800 mL). Additional water was added as required to aid in phase separation. The combined organic phases were dried with sodium sulfate (1000 g) for 16 hours and filtered. The solvent was removed under vacuum to remove the majority of the THF. The solution was filtered through Celite.(R). to remove fine particulates rinsing with diglyme. The diglyme was removed under vacuum (10 mm Hg vacuum, with the bath temperature increased to 60 °C). The residue was placed under high vacuum for 1 hour and then triturated with ether (400 mL). The resulting solids were collected by filtration, washed with ether and dried under vacuum to give the product (100.4 g) as an off white solid.

As the paragraph descriping shows that 5464-12-0 is playing an increasingly important role.

Reference：
Patent; ARRAY BIOPHARMA INC.; BOYS, Mark Laurence; BRADLEY, Michael; DELISLE, Robert Kirk; HENNINGS, D. David; KENNEDY, April L.; MARMSATER, Fredrik P.; MEDINA, Matthew; MUNSON, Mark C.; RAST, Bryson; RIZZI, James P.; RODRIGUEZ, Martha E.; TOPALOV, George T.; ZHAO, Qian; WO2011/79076; (2011); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5464-12-0,5464-12-0, 1-(2-Hydroxyethyl)-4-methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Under an atmosphere of nitrogen gas, l-(2-hydroxyethyl)-4-methylpiperazine (13.93 g) was added to a stirred mixture of 4-(6-chloro-2,3-methylenedioxyanilino)-7-fluoro- 5-tetrahydropyran-4-yloxyquinazoline (12.9 g), sodium te/t-pentoxide (9.87 g) and 1 ,2-diethoxyethane (37.5 ml). Water (1.34 g) and 1,2-diethoxyethane (25 ml) were added and the resultant reaction mixture was stirred and heated to 86°C for 18 hours. The reaction mixture was cooled to 5O0C and, under vacuum distillation at approximately 60 millibar pressure, approximately 50 ml of reaction solvent was distilled off. The reaction mixture was neutralised to pH 7.0 to 7.6 by the addition of a mixture of concentrated aqueous hydrochloric acid (36percent, 10 ml) and water (84 ml) at a rate that kept the temperature of the reaction mixture at a maximum of 6O0C. With the temperature of the reaction mixture being kept at 6O0C, the reaction mixture was extracted with ethyl acetate (225 ml). The organic solution was washed with water (50 ml). Water (25 ml) was added and, with the temperature being kept at 6O0C, the mixture was stirred for 10 minutes, then allowed to stand for 30 minutes and the aqueous layer was separated. The organic layer was concentrated to a volume of about 100 ml by distillation of solvent at about 9O0C under atmospheric pressure. The residual mixture was cooled during 1 hour to 450C and held at that temperature for 2 hours to allow crystallisation of product. The mixture was warmed briefly to 550C and then cooled during 4 hours to 180C EPO and held at that temperature for 1 hour. The crystalline precipitate was isolated by filtration and washed in turn with water (17 ml) and with toe’t-butyl methyl ether (17 ml). There was thus obtained 4-(6-chloro-2,3-piiethylenedioxyanilino)-7-[2-(4-methylpiperazin-l-yl)ethoxy]- 5-tetrahydropyran-4-yloxyquinazoline as a trihydrate (11 g; 88percent purity by HPLC using Method B, retention time 7.3 minutes); NMR Spectrum: (CDCl3) 1.65 (br s, 3H), 1.9-2.05 (m, 2H), 2.2-2.3 (m, 2H), 2.31 (s, 3H), 2.4-2.8 (m, 8H), 2.9 (m, 2H), 3.6-3.7 (m, 2H), 3.95-4.05 (m, 2H), 4.2-4.25 (m, 2H), 4.8 (m,lH), 6.05 (s, 2H), 6.55 (s, IH), 6.75 (d, IH), 6.85 (s, IH), 7.0 (d, IH), 8.55 (s, IH), 9.25 (s, IH).A portion (10 g) of the material so obtained was placed on a filter and dried at ambient temperature in a stream of dry nitrogen gas. The resultant material was dissolved at 6O0C in dry isopropanol (140 ml) whilst maintaining a dry nitrogen atmosphere. The solution was allowed to cool to ambient temperature and to stand under a dry nitrogen atmosphere for 2 days. The resultant crystalline solid was isolated by filtration under a dry nitrogen atmosphere. The material (8 g) so obtained was a crystalline anhydrous form of 4-(6-chloro-2,3-methylenedioxyanilino)-7-[2-(4-methylpiperazin-l -yl)ethoxy]- 5-tetrahydropyran-4-yloxyquinazoline, m.p. 142 to 1440C.

The synthetic route of 5464-12-0 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2006/64217; (2006); A2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5464-12-0,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.5464-12-0,1-(2-Hydroxyethyl)-4-methylpiperazine,as a common compound, the synthetic route is as follows.

(S)-2-( tert-Butoxy)-2-( 4-(4, 4-dimethylpiperidin-l-yl)-2, 6-dimethyl-5-( 4-( 2-( 4- methylpiperazin-l-yl)ethoxy)phenyl)pyridin-3-yl)acetic acid. To a stirred solution of (S)- ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-l-yl)-5-(4-hydroxyphenyl)-2,6- dimethylpyridin-3-yl)acetate (20 mg, 0.043 mmol), 2-(4-methylpiperazin-l-yl)ethanol (30.8 mg, 0.213 mmol) and Ph3P-resin (33.6 mg, 0.128 mmol) in THF (5 mL) was added DEAD (0.020 mL, 0.128 mmol) at rt. After 18 h, mixture was filtered to remove polymer, concentrated and treated with IN NaOH (0.854 mL, 0.854 mmol) in MeOH (1 mL) at 75 °C for 16 h. Mixture was then cooled and purified by prep-HPLC to afford (S)-2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-l-yl)-2,6-dimethyl-5-(4-(2-(4- methylpiperazin-l-yl)ethoxy)phenyl)pyridin-3-yl)acetic acid (2.1 mg, 3.71 mupiiotaomicron, 8.68 percent yield). 1H MR (500MHz, DMSO-d6) delta 7.21 (d, J=8.4 Hz, 1H), 7.05 – 7.00 (m, 3H), 5.80 (s, 1H), 4.22 – 4.04 (m, 2H), 3.36 (br. s., 1H), 2.84 – 2.76 (m, 1H), 2.70 (t, J=5.7 Hz, 2H), 2.43 (s, 3H), 2.33 (br. s., 3H), 2.16 (s, 3H), 2.06 (s, 3H), 1.49 (br. s., 1H), 1.30 (br. s., 1H), 1.17 (d, J=11.4 Hz, 1H), 1.12 (s, 9H), 1.02 (d, J=12.5 Hz, 1H), 0.85 (s, 3H), 0.61 (s, 3H). 8H of piperidine were not resolved. LCMS (M+H) = 567.5

As the paragraph descriping shows that 5464-12-0 is playing an increasingly important role.

Reference：
Patent; VIIV HEALTHCARE UK (NO.5) LIMITED; KADOW, John F.; NAIDU, B. Narasimhulu; PATEL, Manoj; SIVAPRAKASAM, Prasanna; (60 pag.)WO2017/6260; (2017); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics