548762-66-9 | Page 4 of 4 | Heterocyclic Building Blocks-piperazine

New learning discoveries about 548762-66-9

As the paragraph descriping shows that 548762-66-9 is playing an increasingly important role.

548762-66-9, (2S,5R)-tert-Butyl 2,5-dimethylpiperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,548762-66-9

A solution of 6-chloro-1-(3,5-diisopropylpyridazin-4-yl)-7-(2-fluorophenyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (0.439 g, 0.967 mmol, Intermediate 212), phosphoryl trichloride (0.108 mL, 1.16 mmol), and DIPEA (0.168 mL, 0.967 mmol) in acetonitrile (5 mL) was stirred under an air condensor and drying tube at 80 C. for 30 min. The reaction mixture was cooled to RT, and tert-butyl (2S,5R)-2,5-dimethylpiperazine-1-carboxylate (0.207 g, 0.967 mmol; eNovation Chemicals LLC, Bridgewater, N.J.) was added; the solution was stirred a RT for 30 min. The reaction mixture was diluted with EtOAc (200 mL), added to a separatory funnel, and washed with saturated, aqueous sodium bicarbonate (2*100 mL); the organic layer was separated, dried over anhydrous Na2SO4, and concentrated in vacuo. The crude product was adsorbed onto silica and was purified via automated flash chromatography (silica gel. 0-100% EtOAc/heptane) to give tert-butyl (2S,5R)-4-(6-chloro-1-(3,5-diisopropylpyridazin-4-yl)-7-(2-fluorophenyl)-2-oxo-1,2-dihydropyrido[2,3-d]pyrimidin-4-yl)-2,5-dimethylpiperazine-1-carboxylate (258 mg, 0.397 mmol, 41% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) delta 9.11 (d, J=2.3 Hz, 1H) 8.13 (d, J=1.9 Hz, 1H) 7.38-7.47 (m, 1H) 7.05-7.18 (m, 3H) 4.16-5.08 (m, 3H) 3.76-4.08 (m, 2H) 3.45-3.65 (m, 1H) 2.70-2.82 (m, 1H) 2.58-2.70 (m, 1H) 1.52 (s, 9H) 1.24-1.37 (m, 12H) 1.17 (dd, J=9.1, 6.8 Hz, 3H) 1.04 (dd, J=6.7, 4.7 Hz, 3H). 19F NMR (377 MHz, CDCl3) delta -113.34–113.24 (m, 1F). MS (ESI, +ve) m/z: 650.2 (M+1)+.

As the paragraph descriping shows that 548762-66-9 is playing an increasingly important role.

Reference£º
Patent; Amgen Inc.; ALLEN, John Gordon; LANMAN, Brian Alan; CHEN, Jian; REED, Anthony B.; CEE, Victor J.; LIU, Longbin; LOPEZ, Patricia; WURZ, Ryan Paul; NGUYEN, Thomas T.; Booker, Shon; ALLEN, Jennifer Rebecca; CHU-MOYER, Margaret; AMEGADZIE, Albert; CHEN, Ning; GOODMAN, Clifford; LOW, Jonathan D.; MA, Vu Van; MINATTI, Ana Elena; NISHIMURA, Nobuko; PICKRELL, Alexander J.; WANG, Hui-Ling; SHIN, Youngsook; SIEGMUND, Aaron C.; YANG, Kevin C.; TAMAYO, Nuria A.; WALTON, Mary; XUE, Qiufen; US2019/374542; (2019); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

New learning discoveries about 548762-66-9

As the paragraph descriping shows that 548762-66-9 is playing an increasingly important role.

548762-66-9,548762-66-9, (2S,5R)-tert-Butyl 2,5-dimethylpiperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To a stirred solution of 4-fluorobenzoyl chloride(1.0 g, 7.14 mmol) in acetonitrile (10 mL) were added DIPEA (3.74 mL, 21.41 mmol) and HATU (3.53 g, 9.28 mmol) at room temperature. After 30 min., tert-butyl (2S,5R)-2,5-dimethylpiperazine-1- carboxylate (1.83 g, 8.56 mmol) was added and the reaction mixture was stirred overnight. The reaction mixture was concentrated under reduced pressure to remove volatiles and the residue dissolved in ethyl acetate (100 mL) and washed with water (50 mL). The aqueous layer was back extracted with ethyl acetate (100 mL x 2) and the combined organic layer was washed with brine, dried over anhydrous Na2SO4, concentrated under reduced pressure to obtain the crude product, which was purified by silica gel chromatography (50-100% EtOAc in petroleum ether; 40 g column) to afford tert-butyl (2S,5R)-4-(4-fluorobenzoyl)-2,5-dimethylpiperazine-1-carboxylate (1.99 g, 83 % yield). LCMS: m/z = 337.1 (M+H); retention time 1.62 min. [LCMS Condition: Column: Waters Acquity UPLC BEH C18 (2.1 x 50 mm) 1.7 mm, Mobile phase A: 10 mM NH4OAc:acetonitrile (95:5); Mobile phase B: 10 mM NH4OAc:acetonitrile (5:95), Gradient = 20-90 % B over 1.1 minute, then a 0.6 minute hold at 90 % B; Temperature: 50 C; Flow rate: 0.7 mL/min; Detection: UV at 220 nm].

As the paragraph descriping shows that 548762-66-9 is playing an increasingly important role.

Reference£º
Patent; BRISTOL-MYERS SQUIBB COMPANY; VELAPARTHI, Upender; CHUPAK, Louis S.; DARNE, Chetan Padmakar; DING, Min; GENTLES, Robert G.; HUANG, Yazhong; KAMBLE, Manjunatha Narayana Rao; MARTIN, Scott W.; MANNOORI, Raju; MCDONALD, Ivar M.; OLSON, Richard E.; RAHAMAN, Hasibur; JALAGAM, Prasada Rao; ROY, Saumya; TONUKUNURU, Gopikishan; VELAIAH, Sivasudar; WARRIER, Jayakumar Sankara; ZHENG, Xiaofan; TOKARSKI, John S.; DASGUPTA, Bireshwar; REDDY, Kotha Rathnakar; RAJA, Thiruvenkadam; (0 pag.)WO2020/6018; (2020); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

Some tips on 548762-66-9

548762-66-9 (2S,5R)-tert-Butyl 2,5-dimethylpiperazine-1-carboxylate 11745988, apiperazines compound, is more and more widely used in various fields.

548762-66-9, (2S,5R)-tert-Butyl 2,5-dimethylpiperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To a stirred solution of 214 mg (1 mmol) tert-butyl (2S,5R)-2,5-dimethylpiperazine-1- carboxylate in 3.3 mL THF were added at RT 1.74 mL DIPEA (10 mmol, 10 eq) and 194 mg 3- fluorobenzenesulfonyl chloride (1 mmol, 1 eq) and the mixture was stirred for 3 days at RT. The mixture was evaporated to yield 496 mg (133%) of the crude title compound which was used in the next step without further purification. (0532) LC-MS (Method 1): Rt = 1.33 min; MS (ESIpos): m/z = 373 [M+H]+ (0533) 1H-NMR (500 MHz, DMSO-d6) delta [ppm]: 0.84 (3H), 0.99 (3H), 1.38 (9H), 3.09 – 3.19 (3H), 3.54 – 3.67 (3H), 4.03 – 4.31 (2H), 7.56 (1 H), 7.61 – 7.72 (3H)., 548762-66-9

548762-66-9 (2S,5R)-tert-Butyl 2,5-dimethylpiperazine-1-carboxylate 11745988, apiperazines compound, is more and more widely used in various fields.

Reference£º
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; KOPPITZ, Marcus; SIEBENEICHER, Holger; STEUBER, Holger; TER LAAK, Antonius; NUBBEMEYER, Reinhard; ROTTMANN, Antje; IRLBACHER, Horst; BADER, Benjamin; PETERS, Michaele; WAGENFELD, Andrea; (157 pag.)WO2018/114670; (2018); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

Downstream synthetic route of 548762-66-9

As the paragraph descriping shows that 548762-66-9 is playing an increasingly important role.

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.548762-66-9,(2S,5R)-tert-Butyl 2,5-dimethylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

548762-66-9, To a stirred solution of 8.736 g (40.76 mmol) tert-butyl (2S,5R)-2,5-dimethylpiperazine-1 – carboxylate in 30 mL DCM were added at RT 21 .30 mL DIPEA (122.29 mmol, 3 eq) and 13 g 3-fluorobenzenesulfonyl chloride (61.15 mmol, 1 .5 eq) and the mixture was stirred overnight at RT. The organic phase was washed three times with water, dried and evaporated to yield 15.91 g (100%) of the crude title compound which was used in the next step without further purification. (0544) LC-MS (Method 1 ): Rt = 1.37 min; MS (ESIpos): m/z = 391 [M+H]+ (0545) 1H-NMR (400 MHz, DMSO-d6) delta [ppm]: 0.870 (2.76), 0.978 (2.40), 1 .374 (16.00), 2.518 (0.96), 2.523 (0.65), 3.176 (0.83), 3.207 (0.88), 3.360 (2.07), 3.391 (1 .29), 3.581 (0.47), 4.101 (0.61 ), 7.548 (2.26), 7.553 (3.33), 7.556 (2.41 ), 7.565 (2.95), 7.570 (2.61 ), 7.641 (0.55), 7.647 (1.00), 7.653 (0.57), 7.664 (1.16), 7.670 (1 .98), 7.676 (1 .05), 7.687 (0.57), 7.693 (0.96), 7.699 (0.50).

As the paragraph descriping shows that 548762-66-9 is playing an increasingly important role.

Some tips on 548762-66-9

548762-66-9 (2S,5R)-tert-Butyl 2,5-dimethylpiperazine-1-carboxylate 11745988, apiperazines compound, is more and more widely used in various fields.

In a round bottom flask, 2-(chloro(4-fluorophenyl)methyl)-3-fluoropyridine (790 mg, 3.30 mmol) was dissolved in acetonitrile (16.5 mL). To this solution, potassium iodide (54.7 mg, 0.330 mmol), triethylamine (0.919 mL, 6.59 mmol) and tert-butyl (2S,5R)-2,5-dimethylpiperazine-1-carboxylate (706 mg, 3.30 mmol) were added sequentially. After heating at 75 C for 5 hours, TLC in 2:3 ethyl acetate/hexanes showed a trace of starting material and two new compounds of lower rf. LSMS was consistent with 2 major products each having the correct MW corresponding to the two separable diastereomers. The crude material was chromatographed on a 24 g silica gel column with 10-50 % ethyl acetate in hexanes to separate two major fractions labeled Isolate-1 and Isolate-02. LCMS showed that each fraction was consistent with a single diastereomer contaminated with a small amount of the other diastereomer. (1453) Intermediate 157: Isolate-1, First eluting fraction. Analytical LCMS conditions: Injection Vol= 1 mL, Start %B 0, Final %B 100, Gradient Time 2 Minutes, Flow Rate 1 mL/min, Wavelength 220 nm, Solvent Pair Acetonitrile/ Water/ TFA, Solvent A 10 % acetonitrile/ 90 % water/ 0.05% TFA, Solvent B 10 Water 90 % acetonitrile/ 0.05% TFA, Column Acquity BEH C1821. X 50 mm 1.7 mm, Oven Temp= 40 C. LCMS results; retention time 1.27 minutes, observed mass 418.5 (MH+). (1454) Intermediate 158: Isolate-2, Second eluting fraction. Analytical LCMS conditions: Injection Vol= 1 mL, Start %B 0, Final %B 100, Gradient Time 2 Minutes, Flow Rate 1 mL/min, Wavelength 220 nm, Solvent Pair acetonitrile/water/TFA, Solvent A 10 % acetonitrile/90 % water/0.05% TFA, Solvent B 10 Water 90 % acetonitrile/0.05% TFA, Column Acquity BEH C1821. X 50 mm 1.7 mm, Oven Temp= 40 C. LCMS results; retention time 1.31 minutes, observed mass 418.1 (MH+).

548762-66-9 (2S,5R)-tert-Butyl 2,5-dimethylpiperazine-1-carboxylate 11745988, apiperazines compound, is more and more widely used in various fields.

Brief introduction of 548762-66-9

548762-66-9, The synthetic route of 548762-66-9 has been constantly updated, and we look forward to future research findings.

To a stirred solution of 214 mg (1 mmol) tert-butyl (2S,5R)-2,5-dimethylpiperazine-1 – carboxylatein 3.3ml THF were added at RT 1.74 mL DIPEA (10 mmol, 10 eq) and 176 mg benzenesulfonyl chloride (1 mmol, 1 eq) and the mixture was stirred for 3 days at RT. The mixture was evaporated to yield 440 mg (124%) of the crude title compound which was used in the next step without further purification. LC-MS (Method 1 ): Rt = 1 .30 min; MS (ESIpos): m/z = 355 [M+H]+ (0524) 1H-NMR (500 MHz, DMSO-d6) delta [ppm]: 0.81 (3H), 0.99 (3H), 1 .37 (9H), 3.08 – 3.19 (3H), 3.51 – 3.67 (3H), 4.00 – 4.34 (2H), 7.62 (2H), 7.69 (1 H), 7.79 (2H).

548762-66-9, The synthetic route of 548762-66-9 has been constantly updated, and we look forward to future research findings.

Downstream synthetic route of 548762-66-9

As the paragraph descriping shows that 548762-66-9 is playing an increasingly important role.

548762-66-9,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.548762-66-9,(2S,5R)-tert-Butyl 2,5-dimethylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

To a solution of 4,4′-(chloromethylene)bis(fluorobenzene) (3.76 g, 15.75 mmol) in acetonitrile (15 mL) was added tert-butyl (2S,5R)-2,5-dimethylpiperazine-1-carboxylate (2.25 g, 10.50 mmol), followed by DIPEA (5.50 mL, 31.5 mmol). The reaction mixture was stirred at 85 C overnight. The reaction mixture was concentrated under reduced pressure to remove volatiles, the residue was dissolved in ethyl acetate (150 mL), and washed with water. The aqueous layer was back-extracted with ethyl acetate (100 mL x 2). The combined organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure to give the crude product, which was purified by silica gel chromatography on ISCO (5-10 % EtOAc/petroleum ether; 80 g column) to afford tert-butyl (2S,5R)-4-(bis(4-fluorophenyl)methyl)-2,5-dimethylpiperazine-1- carboxylate (3.55 g, 81 % yield). LCMS: m/z = 417.4 (M+H); rt 1.561 min. (LCMS Condition: Column: Kinetex XB-C18 (3 x 75 mm) 2.6 mm; Mobile phase A: 10 mM ammonium formate:acetonitrile (98:2), Mobile phase B: 10 mM ammonium (0508) formate:acetonitrile (2:98), Gradient = 20-100 % B over 4 minutes, then a 0.6 minute hold at 100 % B; Temperature: 27 C; Flow rate: 1.0 mL/min; Detection: UV at 220 nm).

As the paragraph descriping shows that 548762-66-9 is playing an increasingly important role.

Analyzing the synthesis route of 548762-66-9

The synthetic route of 548762-66-9 has been constantly updated, and we look forward to future research findings.

548762-66-9, (2S,5R)-tert-Butyl 2,5-dimethylpiperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

548762-66-9, (b) (2S,5R)-4-[5-(4-Bromo-3-trifluoromethoxy-phenylcarbamoyl)-pyridin-2-yl]-2,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester The product of the previous step (3.86 g, 10.2 mmol) (2S,5R)-2,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester (2.62 g, 12.2 mmol) and N,N-diisopropylethylamine (5.32 mL, 30.5) was dissolved in DMSO (12 mL). The reaction mixture heated at 120 C for 3 h, diluted with EtOAc (100 mL), washed with water, and saturated NH4Cl, water, and brine. The reaction mixture was evaporated to about 40% volume and 3 M HCl in cyclopentyl methyl ether (4.24 mL, 12.7 mmol) was added slowly. Seeds from a previous run at smaller scale were added and the reaction mixture was stirred for 2 days and filtered to provide the HCl salt of the title intermediate (5.15 g, 83 % yield). HPLC method C: Retention time = 21.1 min

The synthetic route of 548762-66-9 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; Theravance Biopharma R&D IP, LLC; MCKINNELL, Robert Murray; LONG, Daniel D.; VAN ORDEN, Lori Jean; JIANG, Lan; LOO, Mandy; SAITO, Daisuke Roland; ZIPFEL, Sheila; STANGELAND, Eric L.; LEPACK, Kassandra; OGAWA, Gavin; HUANG, Xiaojun; ZHANG, Weijiang; EP2635571; (2015); B1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

Simple exploration of 548762-66-9

548762-66-9 (2S,5R)-tert-Butyl 2,5-dimethylpiperazine-1-carboxylate 11745988, apiperazines compound, is more and more widely used in various.

To a solution of(2S,5R)-1-Boc-2,5-dimethylpiperazine (3.5 g, 16.3 mmol, Astatech) in dichloromethane (35 ml), anhydrous triethylamine (4.59 ml, 32.7 mmol) was added and the mixture was cooled to 0 C. in ice-water bath. Acryloyl chloride (1.46 ml, 18.0 mmol) was added dropwise over ?5 min at which point the reaction mixture became yellow and viscous and formation of a white precipitate was observed. Water (10 ml) was added and the mixture was removed from the ice bath and was allowed to stir for 10 min. The organic layer was separated, quickly washed with 2N HCl (40 ml), water and brine, filtered through pad of MgSO4 and concentrated to afford crude tert-butyl (2S,5R)-4-acryloyl-2,5-dimethylpiperazine-1-carboxylate (4.4 g) as yellow oil. This material was redissolved in DCM (40 ml) and TFA (12.6 ml, 163 mmol) was added and the mixture was stirred at rt for 4 h at which point complete deprotection was observed. The mixture was concentrated under reduced pressure and dried under vacuum to afford 1-((2R,5S)-2,5-dimethylpiperazin-1-yl)prop-2-en-1-one 2,2,2-trifluoroacetate (Intermediate 160, ?9 g) as an oil.

548762-66-9 (2S,5R)-tert-Butyl 2,5-dimethylpiperazine-1-carboxylate 11745988, apiperazines compound, is more and more widely used in various.

Analyzing the synthesis route of 548762-66-9

The synthetic route of 548762-66-9 has been constantly updated, and we look forward to future research findings.

548762-66-9, (2S,5R)-tert-Butyl 2,5-dimethylpiperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

548762-66-9, (a) (2S,5R)-4-(5-Methoxycarbonyl-pyridin-2-yl)-2,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester A mixture of 6-fluoronicotinic acid methyl ester (200 mg, 1.29 mmol) and (2S,5R)-2,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester was heated at 120 C. in DMSO (2.0 mL) with potassium carbonate (178 mg, 1.29 mmol) for 2 h. The reaction mixture was partitioned between ethyl acetate (20.0 mL) and water (5.0 mL). The organic layer was washed with water (2*5.0 mL), dried over sodium sulfate, filtered and concentrated to give the title intermediate as a yellowish oil.

The synthetic route of 548762-66-9 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; THERAVANCE, INC.; US2012/114600; (2012); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics