Category: 5464-12-0

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

5464-12-0,5464-12-0, 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, 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, PPh3 (0.0325 mol) was added dropwise at a temperature between 0 and [5°C] to a solution of Vanillin (CA No : [121-33-5)] (0. [025 MOL),] intermediate 14 (0.03 mol) and DIAD (0.0375 mol) in THF (60ml). The mixture was stirred at room temperature for 18 hours. EtOAc was added. The mixture was extracted twice with [HC13N.] The acidic layer was washed with EtOAc, basified with [K,, C03] and extracted with EtOAc. The organic layer was dried [(MGS04),] filtered, and the solvent was evaporated. Yielding: 3.9g of intermediate 15 [(56percent).

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

Reference：
Patent; JANSSEN PHARMACEUTICA N.V.; WO2004/7498; (2004); A2;,
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

Sodium hydride, 60percent dispersion in mineral oil (252 mg, 6.29 mmol) was added, portionwise, to an ice-cooled solution of 2-(4-methyl-piperazin-l-yl)-ethanol (863 mg, 5.99 mmol) and 2-chloro-5- nitropyridine (1.0 g, 6.29 mmol) in DMF (20 ml). The ice-cooling was removed after 1 hour and the mixture was allowed to stir at rt overnight. The reaction mixture was added to ice/water and subsequently extracted with EtOAc (x2). The combined organic extracts were washed with water (x4) and brine (xl), dried and concentrated. The crude product was purified by flash column chromatography on silica gel (60 g) eluting with 10:1 DCM:MeOH to give the product as a brown oil (400 mg, 24percent). 1H NMR (400 MHz, DMSO-^6) delta ppm 2.13 (s, 3 H), 2.21 – 2.54 (m, 8 H), 2.70 (t, /=5.95 Hz, 2 H), 4.50 (t, J=5.95 Hz, 2 H), 7.04 (d, .7=9.16 Hz, 1 H), 8.47 (dd, 7=9.16, 2.75 Hz, 1 H), 9.07 (d, 7=2.29 Hz, 1 H); m/z (ES+APCI)+: 267 [M+H]+.

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

Reference：
Patent; MEDICAL RESEARCH COUNCIL; WO2009/122180; (2009); 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

Sodium hydride, 60percent dispersion in mineral oil (252 mg, 6.29 mmol) was added, portionwise, to an ice-cooled solution of 2-(4-methyl-piperazin-l-yl)-ethanol (863 mg, 5.99 mmol) and 2-chloro-5- nitropyridine (1.0 g, 6.29 mmol) in DMF (20 ml). The ice-cooling was removed after 1 hour and the mixture was allowed to stir at rt overnight. The reaction mixture was added to ice/water and subsequently extracted with EtOAc (x2). The combined organic extracts were washed with water (x4) and brine (xl), dried and concentrated. The crude product was purified by flash column chromatography on silica gel (60 g) eluting with 10:1 DCM:MeOH to give the product as a brown oil (400 mg, 24percent). 1H NMR (400 MHz, DMSO-^6) delta ppm 2.13 (s, 3 H), 2.21 – 2.54 (m, 8 H), 2.70 (t, /=5.95 Hz, 2 H), 4.50 (t, J=5.95 Hz, 2 H), 7.04 (d, .7=9.16 Hz, 1 H), 8.47 (dd, 7=9.16, 2.75 Hz, 1 H), 9.07 (d, 7=2.29 Hz, 1 H); m/z (ES+APCI)+: 267 [M+H]+.

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

Reference：
Patent; MEDICAL RESEARCH COUNCIL; WO2009/122180; (2009); 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

a) 3-Bromo-6-(2-(4-methylpiperazin-1 – l)ethoxy)imidazo[1 ,2-6]pyridazineTo a solution of 2-(4-methylpiperazin-1-yl)ethanol (4.60 g, 32.2 mmol, 1.5 eq) in anhydrous THF (50 mL) was added NaH (60percent in mineral oil, 1.00 g, 42.9 mmol, 2.0 eq) at 0°C and the mixture was stirred at RT. After 1 h, 3-bromo-6-chloro-imidazo[1 ,2-j ]pyridazine (500 mg, 2.14 mmol, 1 eq) was added at 0°C. The mixture was heated to 65°C for 2 h, then allowed to cool, poured into crushed ice and the precipitated solid was collected by filtration to obtain an off-white solid (4.5 g, 62percent); H NMR (400 MHz, DMSO-dB) delta ppm 8.04 (d, J=10.0 Hz, 1 H), 7.74 (s, 1 H), 6.96 (d, J=9.6 Hz, 1 H), 4.46 (t, J=11.6 Hz, 2H), 3.40- 3.30 (m, 4H), 2.74 (t, J=11.6 Hz, 2H), 2.32-2.28 (m, 4H), 2.12 (s, 3H); m/z (APCI)+: 340/342 [M+H]+., 5464-12-0

Big data shows that 5464-12-0 is playing an increasingly important role.

Reference：
Patent; MEDICAL RESEARCH COUNCIL TECHNOLOGY; OSBORNE, Simon; CHAPMAN, Timothy; WALLACE, Claire; WO2012/127212; (2012); 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

To a solution of 70 mg (0.15 mmol) of 4-({2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]butanoyl}amino)benzoic acid (enantiomer 2) in 2 ml of dichloromethane were added, under argon at -20° C., 27 mg (0.19 mmol, 1.25 eq.) of 2-(4-methylpiperazin-1-yl)ethanol, 18 mg (0.15 mmol, 1.0 eq.) of 4-dimethylaminopyridine, 33 mul (0.19 mmol, 1.25 eq.) of N,N-diisopropylethylamine and, finally, 36 mg (0.19 mmol, 1.25 eq.) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride. The reaction mixture was stirred at -20° C. for 20 min and allowed to come to RT, and stirred at RT overnight. After addition of water/dichloromethane and phase separation, the aqueous phase was extracted twice with dichloromethane. The combined organic phases were dried (sodium sulphate), filtered and concentrated under reduced pressure. The residue was purified by means of RP-HPLC (Reprosil C18, acetonitrile/water gradient). Yield: 54 mg (61percent of theory) LC/MS [Method 1]: Rt=0.76 min; MS (ESIpos): m/z=592 (M+H)+, 1H-NMR (400 MHz, DMSO-d6): delta [ppm]=10.83 (s, 1H), 8.00 (d, 1H), 7.93 (d, 2H), 7.78 (d, 2H), 7.76-7.70 (m, 2H), 7.49 (s, 1H), 6.54 (s, 1H), 5.64 (dd, 1H), 4.34 (t, 2H), 3.69 (s, 3H), 2.66 (t, 2H), 2.48-2.40 (m, 4H), 2.35-2.24 (m, 4H), 2.24-2.15 (m, 2H), 2.13 (s, 3H), 0,91 (t, 3H).

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

Reference：
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; ROeHRIG, Susanne; HILLISCH, Alexander; HEITMEIER, Stefan; SCHMIDT, Martina Victoria; SCHLEMMER, Karl-Heinz; TERSTEEGEN, Adrian; TELLER, Henrik; US2018/346424; (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.

Step J: 1-f 2-f 2-Chloro-3-methyl-4-(4, 4, 5, 5-tetramethyl-l, 3, 2-dioxaborolan-2- yl)phenoxy] ethyl] -4-methyl-piperazine (0181) 10.0 g compound of Step I above (37.2 mmol), 8.7 g 2-(4-methylpiperazin-l-yl)ethanol (60.3 mmol) and 15.8 g triphenylphosphine (60.3 mmol) were dissolved in 100 mL dry toluene and then 27 mL diethyl azodicarboxylate (60.3 mmol, 40 percent solution in toluene) was added dropwise. The mixture was stirred at 50 °C under argon until no further conversion was observed. The volatiles were evaporated under reduced pressure and 100 mL diethyl ether was added. The precipitated white crystals were filtered off and washed with diethyl ether. The filtrate was concentrated under reduced pressure and purified via flash chromatography using chloroform and methanol as eluents. The resulting light brown oil was crystallized from hexane to give l-[2-[2-chloro-3-methyl-4-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)phenoxy]ethyl]-4-methyl-piperazine as an off-white solid. 1H NMR (500 MHz, DMSO-d6) delta: 7.56 (d, 1H), 6.99 (d, 1H), 4.15 (t, 2H), 2.72 (t, 2H), 2.51 (s, 3H), 2.50 (br s, 4H), 2.29 (br s, 4H), 2.13 (s, 3H), 1.29 (s, 12H)

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

Reference：
Patent; LES LABORATOIRES SERVIER; VERNALIS (R&D) LIMITED; PACZAL, Attila; SZLAVIK, Zoltan; KOTSCHY, Andras; CHANRION, Maia; MARAGNO, Ana Leticia; GENESTE, Olivier; DEMARLES, Didier; BALINT, Balazs; SIPOS, Szabolcs; (81 pag.)WO2017/125224; (2017); 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

1-(2-Chloroethyl)-4-methylpiperazine (58b) was prepared by refluxing 2-(4- methylpiperazin-1-yl)ethanol (58a) (1.1 g, 7.33 mmol) with thionyl chloride (10 mL). The reaction mixture was cooled to 20 °C, and poured into ice/water. The aqueous solution was then treated with 6-bromo-4-hydroxy-2-methyl-9H-xanthen-9-one (28b) (260 mg, 0.85 mmol), tetrabutylammonium bromide (100 mg), KOH (1.12 g, 20 mmol), and CH2C12 (50mL), and the mixture was stirred for 3 days. The CH2C12 layer was separated, and the aqueous layer was further extracted with CH2C12. The combined CH2C12 extracts were dried (Na2SO4) and the solvent was removed. Chromatography on neutral alumina eluting with 0-20percent hexanes/EtOAc followed by 0-1percent CH2C12/MeOH gave crude material which was re-columned in Si02 eluting with 20percent hexanes/EtOAc to remove impurities, then with0-4percent CH2C12/MeOH to elute 6-bromo-2-methyl-4-(2-(4-methylpiperazin- 1 -yl)ethoxy)-9H- xanthen-9-one (58c): MS (APCI) m/z: 431 and 433 (M+H). This was used directly without further purification., 5464-12-0

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

Reference：
Patent; AUCKLAND UNISERVICES LIMITED; MARSHALL, Andrew James; BUCHANAN, Christina Maree; REWCASTLE, Gordon William; LU, Guo-Liang; FLANAGAN, Jack Urquhart; BONNET, Muriel; SHEPHERD, Peter Robin; JAMIESON, Stephen Michael Frazer; GAMAGE, Swarnalatha Akuratiya; DENNY, William Alexander; (213 pag.)WO2018/83635; (2018); A2;,
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

1-(2-Chloroethyl)-4-methylpiperazine (58b) was prepared by refluxing 2-(4- methylpiperazin-1-yl)ethanol (58a) (1.1 g, 7.33 mmol) with thionyl chloride (10 mL). The reaction mixture was cooled to 20 °C, and poured into ice/water. The aqueous solution was then treated with 6-bromo-4-hydroxy-2-methyl-9H-xanthen-9-one (28b) (260 mg, 0.85 mmol), tetrabutylammonium bromide (100 mg), KOH (1.12 g, 20 mmol), and CH2C12 (50mL), and the mixture was stirred for 3 days. The CH2C12 layer was separated, and the aqueous layer was further extracted with CH2C12. The combined CH2C12 extracts were dried (Na2SO4) and the solvent was removed. Chromatography on neutral alumina eluting with 0-20percent hexanes/EtOAc followed by 0-1percent CH2C12/MeOH gave crude material which was re-columned in Si02 eluting with 20percent hexanes/EtOAc to remove impurities, then with0-4percent CH2C12/MeOH to elute 6-bromo-2-methyl-4-(2-(4-methylpiperazin- 1 -yl)ethoxy)-9H- xanthen-9-one (58c): MS (APCI) m/z: 431 and 433 (M+H). This was used directly without further purification., 5464-12-0

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

Reference：
Patent; AUCKLAND UNISERVICES LIMITED; MARSHALL, Andrew James; BUCHANAN, Christina Maree; REWCASTLE, Gordon William; LU, Guo-Liang; FLANAGAN, Jack Urquhart; BONNET, Muriel; SHEPHERD, Peter Robin; JAMIESON, Stephen Michael Frazer; GAMAGE, Swarnalatha Akuratiya; DENNY, William Alexander; (213 pag.)WO2018/83635; (2018); A2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics