Heterocyclic Building Blocks-piperazine

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.259808-67-8,1-Boc-3,3-Dimethylpiperazine,as a common compound, the synthetic route is as follows.

[Referential Example 281] 4-(tert-Butoxycarbonyl)-1-[(6-chloronaphthalen-2-yl)sulfonyl]-2,2-dimethylpiperazine To a solution of 1-(tert-butoxycarbonyl)-3,3-dimethylpiperazine (125 mg) in methylene chloride (3.0 ml) were added triethylamine (90 ml) and 6-chloronaphthalene-2-sulfonyl chloride (167 mg). The resulting mixture was stirred at room temperature for 84 hours. The reaction mixture was diluted with methylene chloride and added with a saturated aqueous solution of sodium chloride to form two layers. The organic layer obtained by separation was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crudely purified product was purified by chromatography on a silica gel column (hexane: ethyl acetate = 8:1), whereby the title compound (155 mg) was obtained as a colorless solid. 1H-NMR (CDCl3) delta: 1.31(6H,s), 1.44(9H,s), 3.22(2H,br s), 3.49-3.62(2H,br), 3.57-3.62(2H,br), 7.56(1H,dd,J=8.8,2.0Hz), 7.79(1H,d,J=8.8Hz), 7.86(1H,s), 7.87-7.92(3H,m), 8.36(1H,s).

259808-67-8, 259808-67-8 1-Boc-3,3-Dimethylpiperazine 22710387, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; DAIICHI PHARMACEUTICAL CO., LTD.; EP1104754; (2001); 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.122833-04-9,2-Methoxy-4-(4-methylpiperazin-1-yl)aniline,as a common compound, the synthetic route is as follows.

To a solution of compound 8 (1.33 g, 4.66 mmol) and compound11 (1.03 g, 4.66 mmol) in anhydrous 1-butanol (20 mL), trifluoroacetic acid (0.36 mL, 4.66 mmol) was added. The reaction mixturewas heated to 100 C and stirred for 18 h. Subsequently, it wascooled to room temperature and saturated aqueous sodium bicarbonatesolution was added drop wise until basic pH was obtained.The volatiles were removed in vacuo and the obtained thick slurrywas dissolved in DCM (50 mL). The organic layer was washed withwater (20 mL), brine (20 mL), dried over anhydrous sodium sulfate,filtered and concentrated in vacuo. The crude was purified by flashsilica gel chromatography using DCM/MeOH (96:4, v/v) as eluentto afford 1.42 g of the desired product 12 (3.02 mmol, 65%) as white solid., 122833-04-9

122833-04-9 2-Methoxy-4-(4-methylpiperazin-1-yl)aniline 20136253, apiperazines compound, is more and more widely used in various fields.

Reference：
Article; Basu, Debjit; Richters, Andre; Rauh, Daniel; Bioorganic and Medicinal Chemistry; vol. 23; 12; (2015); p. 2767 – 2780;,
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.16154-62-4,1-(2-Chloro-4-nitrophenyl)-4-methylpiperazine,as a common compound, the synthetic route is as follows.

[3-Chloro-4-(4-methyl-1-piperazinyl)phenyl]amine: 1-(2-chloro-4-nitrophenyl)-4- methylpiperazine (13.5 g, 52.8 mmol) was dissolved in Methanol (200 mL), and treated with platinum(IV) oxide (0.120 g, 0.528 mmol). The reaction was evacuated and back filled with H2 twice, then stirred for 48 hours under an H2 atmosphere. The crude mixture was filtered through a pad of celite, washed with MeOH, and concentrated to give the title compound as an orange solid (12 g, 100%). 1H NMR (400 MHz, METHANOL-^) delta ppm 2.35 (s, 3 H) 2.62 (br. s., 4 H) 2.95 (br. s., 4 H) 6.63 (dd, J=8.53, 2.76 Hz, 1 H) 6.75 – 6.81 (m, 1 H) 6.90 – 6.97 (m, 1 H); MS (m/z) 226 (M+H+)., 16154-62-4

16154-62-4 1-(2-Chloro-4-nitrophenyl)-4-methylpiperazine 2837294, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; GLAXO GROUP LIMITED; CASILLAS, Linda, N.; CHAKRAVORTY, Subhas, J.; EIDAM, Patrick; HAILE, Pamela, A.; HUGHES, Terry, Vincent; LAKDAWALA SHAH, Ami; LEISTER, Lara, Kathryn; MILLER, Nathan, Andrew; RAHMAN, Attiq; SEHON, Clark, A.; WANG, Gren, Z.; ZHANG, Daohua; WO2011/120026; (2011); 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.4318-42-7,1-Isopropylpiperazine,as a common compound, the synthetic route is as follows.

1-lsopropylpiperazine (1.8 ml_, 12.7 mmol, 2 equiv) was added to a cold (5°C) solution of 2- chloro-5-nitropyridine (1 g, 6.3 mmol,) in DCM (5 ml_). The reaction mixture was allowed to warm to rt, stirred for 16 h, diluted with DCM and H2O. The aqueous layer was separated and extracted with DCM. The organic phase was washed with brine, dried (Na2SO4), filtered and concentrated to provide 1.58 g of he title compound as a yellow solid: ESI-MS: 251.2 [M+H]+; tR= 2.20 min.

4318-42-7, The synthetic route of 4318-42-7 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; NOVARTIS AG; WO2009/141386; (2009); 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.314741-40-7,(S)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

Sodium hydride (0.86 g, 21 mmol) was added to fert-butyl (3S)-3-(hydroxymethyl)piperazine-l-carboxylate (1.244 g, 5.75 mmol) in THF (40 ml) at rt. The resulting mixture was stirred at rt for 10 min. 7-Bromo-8-chloro-5,6-difluoroquinazolin-4-ol (1.7 g, 5.75 mmol) was added slowly and the resulting solution was stirred at 40C for 1 h. The reaction mixture was quenched with water (2 ml). The reaction mixture was adjusted to pH = 7 with 2M HCI. The crude product was purified by C18-flash chromatography (0 to 65% MeOH in water (0.1% TFA)) to afford ferf-butyl (3S)-3-{[(7-bromo-8-chloro-6-fluoro-4-hydroxyquinazolin-5-yl)oxy]methyl}piperazine-l-carboxylate (1.65 g, 58%) as a brown solid. XH NMR (400 MHz, DMSO) 1.35 (9H, s), 2.62-3.07 (2H, m), 3.11-3.19 (2H, m), 3.20-3.76 (1H, m), 3.80-3.88 (1H, m), 3.98-4.29 (3H, m), 8.23 (1H, s). m/z: ES+ [M+H]+ = 491., 314741-40-7

The synthetic route of 314741-40-7 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; ASTRAZENECA AB; KETTLE, Jason, Grant; BAGAL, Sharanjeet, Kaur; EATHERTON, Andrew, John; FILLERY, Shaun, Michael; ROBB, Graeme, Richard; LAMONT, Scott, Gibson; KEMMITT, Paul, David; GOLDBERG, Frederick, Woolf; (158 pag.)WO2019/215203; (2019); 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.1001180-21-7,(R)-tert-Butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

A flask was equipped with a thermocouple, mechanic stirrer, a nitrogen inlet and drying tube. To the flask was added (R)-tert-buty 4-(5-methyl-7-oxo-6,7-dihydro-5H- cyclopenta[i ]pyrimidin-4-yl)piperazine-l -carboxylate (46.0 g, 139 mmol) followed by dichloromethane (1.10 L) and RuCl(TsDACH) catalyst (1.50 g, 2.80 mmol) with nitrogen degassing (gas dispersion tube) and agitation at room temperature. To the mixture was added triethylamine (23.0 mL, 167 mmol) with degassing. Formic acid (7.40 mL, 195 mmol) was slowly added to the mixture at a rate of about 1 mL/min. Good agitation with stirring was maintained until complete consumption of starting material (about 8-12 hr) as determined by HPLC analysis. The reaction was quenched with saturated sodium bicarbonate (2.00 vol., 100 mL), the layers were separated and the aqueous layer was discarded. The organic layer was washed with saturated sodium bicarbonate, saturated ammonium chloride and brine (2.00 vol., 100 mL each). The organics were dried over sodium sulfate, filtered and solvent exchanged into methanol. The methanolic solution (5.00 vol.) of crude product was charged with 50 wt % SiliaBond Thiol (Silicycle, Inc.) and 20 wt% Charcoal. The mixture was heated to about 50 C and maintained at that temperature with good stirring overnight. The mixture was cooled to room temperature, filtered over a pad of Celite and then polish filtered through a 0.45 micron filter. The mixture was distilled to a minimum working volume and concentrated under reduced pressure to afford the product (44.0 g, 95 % yield), as a 96:4 mixture of trans/cis diastereomers) as solid. Trace amount of Ru metal was measured by ICP-EOS and found that the product contained less than about 20 ppm Ru. The product was purified by preparative HPLC under the following conditionsor crystallization from ethyl acetate/heptane to yield 98.4 % pure product, 97.7 % de with about 100% ee., 1001180-21-7

The synthetic route of 1001180-21-7 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; ARRAY BIOPHARMA INC.; GENENTECH, INC.; LANE, Jonathan W.; REMARCHUK, Travis; SHAKYA, Sagar; SPENCER, Keith L.; STENGEL, Peter J.; WO2013/173736; (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.120737-59-9,tert-Butyl 3-methylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

120737-59-9, TO a solution of 2-cyclohexylamino-4, 6-dichloro-1, 3,5-triazine (example 7, step A) (706mg) in DCM (5mL) at 0°C was added 3-METHYL-PIPERAZINE-1-CARBOXYLIC acid tert- butyl ester (579mg) and DIPEA (502PL). The mixture was allowed to warm to room temperature and stirred for 1 hour. The mixture was extracted with DCM (20mL) and washed with HCl (20ml), 1M), solvent was then removed under reduced pressure to yield 2-CHLORO-4-CYCLOHEXYLAMINO-6- (4-TERT-BUTOXYCARBONYL-2-METHYLPIPERAZIN-1-YL)- 1,3, 5-triazine (840mg) as a white powder. MS M/Z 411. 0 (M+1).

The synthetic route of 120737-59-9 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; AKZO NOBEL N.V.; WO2005/11703; (2005); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

303-26-4, 1-((4-Chlorophenyl)(phenyl)methyl)piperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Example 1 : Preparation of5-(4-((4-chlorophenyl)(phenyl)methyl)piperazin-l-yl)-N-(4-methylbenzyl)-3-meth yl-5-oxopentanamide; [147] [148] 0.5 mmol of 4-(4-methylbenzylcarbamoyl)-3-methylbutanoic acid prepared inPreparative Example 1, 0.55 mmol of l-(4-chlorobenzhydryl)piperazine, and ben- zotriazol-1-yloxytripyrrolidino phosphonium hexafluorophosphate (PyBOP) were added to 3 mL of dimethylformamide (DMF) to dissolve. Then, 1.0 mmol of N,N-diisopropylethylamine (DIEA) was added thereto, and stirred at room temperature for 16 hours. 20 mL of 10% HCl was put into the reaction solution, and extracted with 30 mL of EtOAc. The organic layer was washed with 20 mL of 10% HCl, and then washed with 20 mL of a saturated NaHCO solution twice and with 20 mL of a saturated NaCl solution twice. The organic layer was collected, dried over anhydrous MgSO 4 , and filtered under reduced pressure. The organic solvent in the filtrate was removed under reduced pressure. The residue was purified by column chromatography with a mixed solvent of EtOAc and methanol (20:1), so as to obtain the title compound (light yellow solid, yield: 65%).[149] mp 62-630C;[150] 1U NMR (CDCl ) delta 7.35 (d, J=8.0 Hz, 2CH), 7.29 (d, J=7.2 Hz, 2CH), 7.26 (t, J=8.2 Hz, 2CH), 7.22 (t, J=7.3 Hz, CH), 7.16 (d, J=8.0 Hz, 2CH), 7.11 (d, J=7.2 Hz, 2CH), 6.29 (s, NH), 4.37 (d, J=5.6 Hz, CH2), 4.21 (s, CH), 3.59 (t, J=5.6 Hz, CH2), 3.48 (q, J=5.6 Hz, CH2), 2.43 (d, J=6.8 Hz, CH2), 2.34-2.39 (m, CH2), 2.32 (s, CH3), 2.28 (d, J=6.0 Hz, CH ), 2.25 (d, J=6.4 Hz, CH ), 2.13-2.23 (m, CH), 1.03 (d, J=6.4 Hz, CH3);[151] HR-FABMS Calcd for C H ClN O : (M++l): 518.2574, Found: 518.2584.31 36 3 2

303-26-4, As the paragraph descriping shows that 303-26-4 is playing an increasingly important role.

Reference：
Patent; PARK CHOO, Hea-Young; WO2007/142431; (2007); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

21655-48-1, cis-2,6-Dimethylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

cis-3,5-Dimethyl-1-(4-trifluoromethoxy-benzyl)-piperazine: To a solution of 4-(trifluoromethoxy)-benzaldehyde (776 uL, 4.38 mmol) in methylene chloride (30 mL) was added cis-2,6-dimethyl piperazine (1.0 g, 8.77 mmol). After 1 hour sodium triacetoxy borohydride (2.45 g, 8.77 mmol) was added to the mixture. The solution was stirred at room temperature for an additional 4 hours. The reaction was concentrated in vacuo, diluted with ethyl acetate and extracted with 1N HCl (2.x.50 mL). The aqueous layer was then neutralized with NaOH and extracted with ethyl acetate (3.x.50 mL). The organic layer was dried (Na2SO4) and concentrated to provide cis-3,5-dimethyl-1-(4-trifluoromethoxy-benzyl)-piperazine (1.01 g, 80percent). 1H NMR (400 MHz, CD3OD) delta 7.42 (d, 2H), 7.23 (d, 2H), 3.54 (s, 2H), 2.98-2.88 (m, 2H), 2.82-2.74 (m, 2H), 1.69 (t, 2H), 1.05 (d, 6H); LCMS 289.5 (M+1)+.

21655-48-1, 21655-48-1 cis-2,6-Dimethylpiperazine 6950261, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; KALYPSYS, INC.; US2008/4281; (2008); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics