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, A suspension of 60percent Sodium hydride in mineral oil (131.3 mg, 3.28 mmol) was washed with anhydrous hexane (5 mL) and suspended in anhydrous DMF (5 mL). l-(2- Hydroxyethyl)-4-methylpiperizine (473.6 mg, 3.28 mmol) was dissolved in DMF (5 mL) and added slowly to the above suspension at room temperature. The reaction mixture was stirred for 1 h at room temperature. Compound 99 (397 mg, 0.831 mmol) in DMF (5 mL) was slowly added to the reaction mixture. The reaction mixture was stirred for 3 h at room temperature. Ice water (25 mL) was added and the suspension was extracted with chloroform (2 x 100 mL). The solvent was removed under vacuum. After silica gel column chromatography (chloroform: methanol (9:1)), the resulting compound was dissolved in acetone (5 mL) and acidic solution (10 mL, acetone: 3N HCl (3:1)) was added. The reaction was stirred for 1 h at room temperature. The solvent was removed under vacuum and the pH was adjusted to 10 with concentrated ammonium hydroxide solution and extracted with chloroform (2 x 50 mL). The solvent was removed under vacuum. After silica gel column chromatography (methanol: cone, ammonium hydroxide (20:1)), the resulting compound was purified on alumina (dichloromethane: methanol (25:1)) to yield (CDD-0356) compound 113 (146 mg, 34.33percent) as a colorless oil. The free base CDD-0356 (113) was treated with fumaric acid in ethanol to yield the difumarate salt CDD-0356 (114) (130 mg) as white solid. CDD-0356F; 1H NMR (D2O): delta 1.49-1.67 (6H, m), 1.85-2.0 (4H, m), 2.26-2.32 (IH, m), 2.72 (3H, s), 2.76-3.6 (28H, m), 3.74-3.82 (IH, m), 4.26-4.34 (2H, m), 6.46 (4H, s).13C NMR (D2O/CD3OD): delta 19.05, 23.70, 24.22, 29.20, 29.61, 29.63, 29.7, 34.91, 34.93, 43.82(m), 47.3, 47.55, 50.1, 50.47 (m), 52.38 (m), 56.83, 56.85, 66.22 (m), 67.93, 67.97, 68.36, 68.37, 68.44, 68.48, 68.73, 68.74, 68.96, 135.73, 151.26, 163.31, 172.40. Anal: [C33H55N5Oi3S] C, H, N.

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

Reference：
Patent; UNIVERSITY OF TOLEDO; WO2009/152392; (2009); 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, 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, 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 25 mL round bottom flask equipped with a stir bar was added 2-(4-methyl-piperazin-1-yl)-ethanol (0.079 mL, 0.65 mmol) and DMF (5 mL) and the solution was cooled to 0° C. in an ice-water bath after which sodium hydride (0.026 g, 0.65 mmol, 60percent oil dispersion) was added. The solution was allowed to stir at 0° C. for 20 minutes after which 2-methanesulfonyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid [2-chloro-5-(3-chloro-benzylcarbamoyl)-phenyl]-amide (0.050 g, 0.093 mmol) (from Example 75 supra) was added all at once. The reaction was allowed to warm to room temperature and stir for 16 hours. The reaction was filtered and then purified by reverse-phase HPLC (Gilson, C-18 Polaris column; eluting with 30-100percent acetonitrile/water with 0.1percent TFA) to provide, after basification to remove the TFA, 2-[2-(4-methyl-piperazin-1-yl)-ethoxy]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid [2-chloro-5-(3-chloro-benzylcarbamoyl)-phenyl]amide. (Yield 0.010 g, 18percent). LR-MS: [M+H]+: 610.

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

Reference：
Patent; Anderson, Kevin; Chen, Yi; Chen, Zhi; Luk, Kin-Chun; Rossman, Pamela Loreen; Sun, Hongmao; Wovkulich, Peter Michael; US2012/184542; (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, 10.0 g Preparation B2 (37.2 mmol), 8.7 g 2-(4-methylpiperazin-1-yl)ethanol (60.3 mmol) and 15.8 g PPh3 (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 Et20 was added. Theprecipitated white crystals were filtered off and washed with Et20. The filtrate was concentrated under reduced pressure and purified via flash chromatography using CHC13 and MeOH as eluents. The resulting light brown oil was crystallized from hexane to give Preparation B4 as an off-white solid. 1H NMR (500 MHz, DMSO-d6) oe: 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; SZLAVIK, Zoltan; SZABO, Zoltan; CSEKEI, Marton; PACZAL, Attila; KOTSCHY, Andras; BRUNO, Alain; GENESTE, Olivier; CHEN, I-Jen; DAVIDSON, James Edward Paul; MURRAY, James Brooke; ONDI, Levente; RADICS, Gabor; SIPOS, Szabolcs; PROSZENYAK, Agnes; PERRON-SIERRA, Francoise; BALINT, Balazs; (188 pag.)WO2016/207226; (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

To a 25 mL round bottom flask equipped with a stir bar was added 2-(4-methyl-piperazin-1-yl)-ethanol (0.079 mL, 0.65 mmol) and DMF (5 mL) and the solution was cooled to 0° C. in an ice-water bath after which sodium hydride (0.026 g, 0.65 mmol, 60percent oil dispersion) was added. The solution was allowed to stir at 0° C. for 20 minutes after which 2-methanesulfonyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid [2-chloro-5-(3-chloro-benzylcarbamoyl)-phenyl]-amide (0.050 g, 0.093 mmol) (from Example 75 supra) was added all at once. The reaction was allowed to warm to room temperature and stir for 16 hours. The reaction was filtered and then purified by reverse-phase HPLC (Gilson, C-18 Polaris column; eluting with 30-100percent acetonitrile/water with 0.1percent TFA) to provide, after basification to remove the TFA, 2-[2-(4-methyl-piperazin-1-yl)-ethoxy]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid [2-chloro-5-(3-chloro-benzylcarbamoyl)-phenyl]amide. (Yield 0.010 g, 18percent). LR-MS: [M+H]+: 610.

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

Reference：
Patent; Anderson, Kevin; Chen, Yi; Chen, Zhi; Luk, Kin-Chun; Rossman, Pamela Loreen; Sun, Hongmao; Wovkulich, Peter Michael; US2012/184542; (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, 10.0 g Preparation B2 (37.2 mmol), 8.7 g 2-(4-methylpiperazin-1-yl)ethanol (60.3 mmol) and 15.8 g PPh3 (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 Et20 was added. Theprecipitated white crystals were filtered off and washed with Et20. The filtrate was concentrated under reduced pressure and purified via flash chromatography using CHC13 and MeOH as eluents. The resulting light brown oil was crystallized from hexane to give Preparation B4 as an off-white solid. 1H NMR (500 MHz, DMSO-d6) oe: 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; SZLAVIK, Zoltan; SZABO, Zoltan; CSEKEI, Marton; PACZAL, Attila; KOTSCHY, Andras; BRUNO, Alain; GENESTE, Olivier; CHEN, I-Jen; DAVIDSON, James Edward Paul; MURRAY, James Brooke; ONDI, Levente; RADICS, Gabor; SIPOS, Szabolcs; PROSZENYAK, Agnes; PERRON-SIERRA, Francoise; BALINT, Balazs; (188 pag.)WO2016/207226; (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, 10.373 g 4-bromo-2-chlorophenol (50 mmol), 14.442 g 2-(4-methylpiperazin-l-yl)ethanol (100 mmol) and 26.229 g PPh3 (100 mmol) were dissolved in 250 mL dry toluene under N2 atmosphere, then 23.027 g DTAD (100 mmol) was added. The mixture was stirred at 50 °C until no further conversion was observed. The volatiles were evaporated under reduced pressure and the residue was purified via flash chromatography using EtOAc and MeOH as eluents. MS (M+H): 333.0

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

Reference：
Patent; LES LABORATOIRES SERVIER; VERNALIS (R&D) LIMITED; BALINT, Balazs; CSEKEI, Marton; SZABO, Zoltan; SZLAVIK, Zoltan; KOTSCHY, Andras; CHANRION, Maia; GENESTE, Olivier; CHEN, I-Jen; DAVIDSON, James Edward Paul; MURRAY, James Brooke; SIPOS, Szabolcs; ONDI, Levente; PROSZENYAK, Agnes; (164 pag.)WO2016/207217; (2016); 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.

EXAMPLE 22: 2-Chloro-6-(2-(4-methylpiperazin- 1 -yl)methoxy)pyridine31To a suspension of 2-(4-methylpiperazine-l-yl)ethanol (50mg, 0.347mmol) in dioxane (3ml) at 0°C, KOlBu (50mg, 0.347mmol) was added and the reaction mixture was stirred for lOmin. Ice bath was removed and the reaction mixture was allowed to attain room temperature. The mixture was again cooled to 0°C and 2, 6-Dichloropyrazine (200mg, 1.04mmol) was added. Reaction mixture was allowed to stir at RT for 24h after which it was concentrated and was purified by flash column chromatography over 230-400 silica gel using 5-8percent MeOH/DCM system to afford the desired product 31, 30mg (Yield:35 percent) as brown gummy liquid. The product was confirmed by 1HNMR (not clean but characteristic peaks were present); MS: 256, (M+l), LCMS -90percent.

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

Reference：
Patent; ARRIEN PHARMAEUTICALS LLC; VANKAYALAPATI, Hariprasad; APPALANENI, Rajendra, P.; REDDY, Y., Venkata Krishna; WO2012/135631; (2012); 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.

Sodium hydride (60percent, 0.87 g, 21.80 mmol) was added to diglyme (10 mL). A solution of 2-(4-methyl-piperazin-1-yl)-ethanol (3.14 g, 21.80 mmol) in diglyme (10 mL) was added slowly. The reaction mixture was heated at 40 00 for 1 hour, 4-chloro-pyridin- 2-ylamine (1.40 g, 10.9 mmol) was added and the reaction mixture was heated at 8000 for 1 hour, then at 15700 for 16 hours. The reaction mixture was cooled, diluted with water (20 mL), and THF (20 mL) was added, then NaCI. The organic phase was separated, and the aqueous phase was extracted with THF. The combined organic phase was dried, and the solvent was evaporated. Diethyl ether was added to the residue. The resulting solid was filtered, washed with ether, and dried to afford a white solid (1.86 g, 72percent), (M+H)=237.

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

Reference：
Patent; ASTEX THERAPEUTICS LIMITED; SAXTY, Gordon; MURRAY, Christopher William; BERDINI, Valerio; PAGE, Lee William; ROOMANS, Susan; TAMANINI, Emiliano; BUCK, Ildiko Maria; DAY, James Edward Harvey; CARR, Maria Grazia; LEE, Lydia Yuen Wah; WO2015/4481; (2015); 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.

Sodium hydride (60percent, 0.87 g, 21.80 mmol) was added to diglyme (10 mL). A solution of 2-(4-methyl-piperazin-1-yl)-ethanol (3.14 g, 21.80 mmol) in diglyme (10 mL) was added slowly. The reaction mixture was heated at 40 00 for 1 hour, 4-chloro-pyridin- 2-ylamine (1.40 g, 10.9 mmol) was added and the reaction mixture was heated at 8000 for 1 hour, then at 15700 for 16 hours. The reaction mixture was cooled, diluted with water (20 mL), and THF (20 mL) was added, then NaCI. The organic phase was separated, and the aqueous phase was extracted with THF. The combined organic phase was dried, and the solvent was evaporated. Diethyl ether was added to the residue. The resulting solid was filtered, washed with ether, and dried to afford a white solid (1.86 g, 72percent), (M+H)=237.

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

Reference：
Patent; ASTEX THERAPEUTICS LIMITED; SAXTY, Gordon; MURRAY, Christopher William; BERDINI, Valerio; PAGE, Lee William; ROOMANS, Susan; TAMANINI, Emiliano; BUCK, Ildiko Maria; DAY, James Edward Harvey; CARR, Maria Grazia; LEE, Lydia Yuen Wah; WO2015/4481; (2015); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics