Heterocyclic Building Blocks-piperazine

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.630125-91-6,4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline,as a common compound, the synthetic route is as follows.

To a stirred solution of 4-((4-ethylpiperazin- 1 -yl)methyl)-3-(trifluoromethyl)aniline (Intermediate Cl) (150 mg, 0.52 mmol) in THF (20 mL) was added triphosgene (54 mg, 0.18 mmol) and the resulting mixture was stirred at 70 C. After 1 h of heating the mixture wasconcentrated under reduced pressure and the residue was dissolved in THF (20 mL). That solution was added dropwise to a stirred mixture of tert-butyl 4-(5-amino-2-chlorophenoxy)- 6H-pyrimido [5,4-b] [1 ,4]oxazine-8(7H-carboxylate (step 1 intermediate) (150 mg, 0.40 mmol) and triethylamine (172 jiL, 1.19 mmol) in THF (20 mL) at RT. The resultant mixture was stirred for 2 h at 70 C. The mixture was cooled to RT and quenched with water. Theaqueous mixture was extracted twice with ethyl acetate. The combined organic layers were washed with water followed by brine. The solution was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue thus obtained was purified by silica gel column chromatography to yield 100 mg of the desired product. ?H NMR (400 MHz, DMSO-d6) oe 1.09 (t, J= 7.2 Hz, 3H), 1.50 (s, 9H), 2.42-2.5 1 (m, 1OH), 3.54 (br s, 2H),3.94 (t, J= 8.4 Hz, 2H), 4.40 (t, J= 7.6 Hz, 2H), 7.29 (dd, J, = 2.4 Hz, J2 = 8.0 Hz, 1H), 7.48(d, J 8.8 Hz, 1H), 7.55-7.94 (m, 3H), 7.95 (s, 1H), 8.05 (s, 1H), 9.15 (s, 1H), 9.20 (s, 1H)., 630125-91-6

The synthetic route of 630125-91-6 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; GLENMARK PHARMACEUTICALS S.A.; PATEL, Vinod; REDDY, Venkateshwar; GHARAT, Laxmikant Atmaram; CHAUDHARI, Sachin Sundarlal; DAS, Sanjib; VELGALETI, Ranganadh; SHAH, Daisy Manish; BAJPAI, Malini; (262 pag.)WO2018/215668; (2018); 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.655225-01-7,tert-Butyl 4-(2-bromoethyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

Step 1. 5-Bromo-4-(cyclobutylmethoxy)-1-methyl-3-(2-piperazin-1-ylethyl)-1,3-dihydro-2H-benzimidazol-2-one A solution of 5-bromo-4-(cyclobutylmethoxy)-1-methyl-1,3-dihydro-2H-benzimidazol-2-one (250 mg, 0.803 mmol) in N,N-dimethylformamide (7.96 mL) was treated with cesium carbonate (1.31 g, 4.02 mmol) followed by the addition of tert-butyl 4-(2-bromoethyl)piperazine-1-carboxylate (471 mg, 1.61 mmol), and the resultant reaction mixture was stirred at 60° C. overnight, after which time the LCMS analysis of the reaction mixture indicated complete conversion of the starting materials. The reaction mixture was diluted with ethyl acetate and water. Layers were separated and the organic layer was washed with brine, dried with magnesium sulfate, filtered, and concentrated in vacuo to give the crude intermediate tert-butyl carboxylate, which was used in further step without purification., 655225-01-7

The synthetic route of 655225-01-7 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; INCYTE CORPORATION; Yue, Eddy W.; Combs, Andrew P.; Douty, Brent; US2015/148342; (2015); 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.303-26-4,1-((4-Chlorophenyl)(phenyl)methyl)piperazine,as a common compound, the synthetic route is as follows.

Example 29 : Preparation of N-(4-methylbenzyl)-5-(4-((4-chlorophenyl)(phenyl)methyl)piperazin-l-yl)-3,3-dimet hyl-5-oxopentanamide; [409][410] 0.5 mmol of 4-(4-methylbenzylcarbamoyl)-3,3-dimethylbutanoic acid prepared inPreparative Example 14, 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 3 solution twice and with 20 mL of a saturated NaCl solution twice. The organic layer was collected, dried over anhydrousMgSO , and filtered under reduced pressure. The organic solvent in the filtrate was4 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: 70%). [411] mp 63-64C;[412] 1U NMR (CDCl ) delta 8.05 (t, J=5.8 Hz, NH), 7.35 (d, J=8.0 Hz, 4CH), 7.30 (d, J=7.2Hz, 3CH), 7.26 (t, J=8.4 Hz, 2CH), 7.18 (d, J=8.0 Hz, 2CH), 7.10 (d, J=8.0 Hz, 2CH), 4.38 (d, J=5.6 Hz, CH2), 4.20 (s, CH), 3.56-3.66 (m, CH2), 3.51 (t, J=5.0 Hz, CH2),2.34-2.37 (m, 2CH ), 2.33 (s, CH ), 2.32 (s, 2CH ), 1.02 (s, 2CH ); [413] HR-FABMS Calcd for C 32 H 38 ClN 3 O 2 : (M++l): 532.2731, Found: 532.2719.

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

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.57260-71-6,tert-Butyl piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

57260-71-6, The production of compound No. 26 proceeds according to the sequence of reaction steps shown in the following schemes: The first sub-step shown above was performed at 20 C. during 2 hours with a molar excess of CH2N2 (about 2 molar equivalents) in dry ether, then in a second sub-step (shown below) performed at 5 C. HCl gas was bubbled into the reaction mixture for 15 minutes, and the desired intermediate was obtained in 71% yield. For the conversion from 3 to 4, the first sub-step shown above was performed at 20 C. during 1 hour with a molar excess of thio-carbonyldiimidazole (about 2 molar equivalents) in THF, then in a second sub-step performed at 20 C. for 12 hours a 25% aqueous NH3 solution was added, and the desired intermediate was obtained in 72% yield. The conversion from 4 to 5 was performed during 6 hours with 1 molar equivalent NaHCO3 at reflux in methanol, and the desired intermediate was obtained in 92% yield. The conversion from 5 to 6 was performed during 3 hours at 20 C., and the desired intermediate was obtained in 90% yield. The conversion from 6 to the final compound was performed during 6 hours at 20 C. in 1,2-dichloroethane (DCE) in the presence of a molar excess of triethylamine (1.2 molar equivalents).

As the paragraph descriping shows that 57260-71-6 is playing an increasingly important role.

Reference：
Patent; NV reMYND; US2010/197703; (2010); 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.103-76-4,N-(2-Hydroxyethyl)piperazine,as a common compound, the synthetic route is as follows.

In a three-neck round-bottomed flask, 1-(2-hydroxyethyl)piperazine (3.00 g, 23.05 mmol) was dissolved in 15 mL of water. A solution of benzylchloroformate (3.95 mL, 27.66 mmol) in 15 mL of acetonitrile was added dropwise via isobar cylindrical funnel. In order to maintain the pH around 9, a solution of 4N NaOH was added dropwise via a second isobar cylindrical funnel. The reaction mixture was stirred overnight at RT and then extracted with DCM (2 x 75 mL). The aqueous phase containing the final compound was acidified with 3N HCl and extracted with DCM (3 x 75 mL). Organic extracts were combined, washed with brine (150 mL), dried over anhyd. sodium sulfate and concentrated under vacuum. The crude was purified by flash chromatography (0 to 2% of MeOH in DCM) to afford 18 (5.41g, 90%) as a colorless oil. 1H-NMR (500 MHz, DMSO, delta): 7.37-7.29 (m, 5H, CH arom.), 5.05 (s, 2H, CH2Phi), 4.41 (s, 1H, OH), 3.49 (m, 2H, CH2OH), 3.35 (m, 4H, (CH2)2N(Z)), 2.36 (m, 6H, CH2N, CH2NCH2). 13C-NMR (100.6 MHz, DMSO, delta): 115.04, 137.59, 129.09, 128.49, 128.22, 66.81, 60.83, 59.14, 53.51, 44.16. MS (ESI) m/z 265.00 (M + H)+., 103-76-4

As the paragraph descriping shows that 103-76-4 is playing an increasingly important role.

Reference：
Article; Denoyelle, Severine; Chen, Ting; Chen, Limo; Wang, Yibo; Klosi, Edvin; Halperin, Jose A.; Aktas, Bertal H.; Chorev, Michael; Bioorganic and Medicinal Chemistry Letters; vol. 22; 1; (2012); p. 402 – 409;,
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.502649-32-3,1-Boc-3-Isopropylpiperazine,as a common compound, the synthetic route is as follows.

502649-32-3, A mixture of 10- hydroxy-10-((6-oxo-4-phenylpyrimidin-1 (6/-/)-yl)methyl)-7-azaspiro[4.5]decane-7-carbonyl chloride (10 mg, 0.0249 mmol), tert- butyl 3-isopropylpiperazine-1-carboxylate (8.5 mg, 0.0373 mmol) and DIPEA (13 mI_, 0.0746 mmol) in DCM (0.5 mL) was stirred at rt for 2 h 30 min before tert- butyl 3-isopropylpiperazine-1-carboxylate (8.5 mg, 0.0373 mmol) and DIPEA (13 pL, 0.0746 mmol) were added. The reaction was stirred for further 18 h 45 min before DMF (0.5 mL) was added and the reaction stirred for a further 6 days. The reaction mixture was diluted with saturated NaHC03(aq) (15 mL) and the resulting mixture was extracted with DCM (3 x 10 mL) using a phase separator. The combined organic phases were concentrated under reduced pressure and the residue was purified by flash (1504) chromatography (0-100% EtOAc in cyclohexane) to give the title compound (7.7 mg, 52%) as colourless glass. LCMS (Method A): RT = 1.70 min, m/z = 594 [M+H]+.

502649-32-3 1-Boc-3-Isopropylpiperazine 44558596, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; ALMAC DISCOVERY LIMITED; ROUNTREE, James Samuel Shane; WHITEHEAD, Steven Kristopher; TREDER, Adam Piotr; PROCTOR, Lauren Emma; SHEPHERD, Steven David; BURKAMP, Frank; COSTA, Joana Rita Castro; O’DOWD, Colin; HARRISON, Timonthy; (333 pag.)WO2019/150119; (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.314741-40-7,(S)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

Step C: tert-butyl(3S)-3-(hydroxymethyl)-4-[2-hydroxy-2-( 1-oxo- 1 ,3-dihydro-2-benzofuran-5-yl)ethyll piperazine- 1 -carboxylate: 5- (Oxiran-2-yl)-2-benzofuran- 1 (3H)-one (1.5 g, 8.5 mmol)and commercially available (S)-4-N-BOC-2-hydroxymethyl piperazine (2.394 g, 11.07 mmol)were combined in ethanol (10 mL) in a microwave tube. The mixture was degas sed then heated for 60 mm at 150 C. LC-MS showed the product peak. The reaction was worked up by adding ethyl acetate and washing once with brine. The organic layer was separated, dried, andconcentrated to dryness. The crude product was purified by MPLC using an 80g Redi-sep column and eluted with 50%-i 00% EtOAc hexane yielding the title compound.

314741-40-7, As the paragraph descriping shows that 314741-40-7 is playing an increasingly important role.

Reference：
Patent; MERCK SHARP & DOHME CORP.; PASTERNAK, Alexander; DEJESUS, Reynalda, Keh; FRIE, Jessica, L.; PIO, Barbara; TANG, Haifeng; WALSH, Shawn, P.; WO2014/99633; (2014); A2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

314741-40-7, (S)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

60% Sodium hydride (0.7 g, 17.51 mmol) was added portionwise to te/t-butyl (5)-3- (hydroxymethyl)piperazine-l-carboxylate (1.89 g, 8.76 mmol) and 7-bromo-6-chloro-5- fluoroquinazolin-4-ol (2.03 g, 7.3 mmol) in THF (50 ml) cooled to 0C. The resulting mixture was stirred at 0C for 5 minutes, allowed to warm to room temperature then heated to 65C and stirred for 2 hours. A further 60% sodi um hydride (0.07 g, 1.75 mmol) was added to ieri-butyl (S)-3- (hydroxymethyl)piperazine-l-carboxylate (0.19 g, 0.88 mmol) in THF (2 ml) at room temperature. This was stirred for 10 minutes then this solution was added to the reaction mixture then stirred for a further 1 hour at 65C and allowed to cool to room temperature with stirring overnight. The reaction mixture was diluted with EtOAc (200 ml), and water (20 ml). The aqueous phase was taken to pH5 with acetic acid, then taken to pH 8 with NaHCC>3 and the two phases separated. The aqueous phase was extracted with EtOAc (100 ml). The organic phases were combined, dried and reduced. The residue was purified by flash silica chromatography, elution gradient 0 to 20% MeOH in DCM. Pure fractions were evaporated to dryness to afford te/t-butyl (5)-3-(((7-bromo-6-chloro-4- hydroxyquinazolin-5-yl)oxy)methyl)piperazine-l-carboxylate (2.64 g, 76%) as a white foam. IH NM (500 M Hz, DMSO, 27C) 1.39 (9H, s), 2.52 – 2.84 (3H, m), 2.88 (IH, dt), 2.96 (IH, dd), 3.74 (IH, d), 3.93 (2H, d), 4.05 (2H, d), 7.84 (IH, s), 8.09 (IH, s). m/z: ES+ [M+H]+ 473, 314741-40-7

314741-40-7 (S)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate 24820294, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; ASTRAZENECA AB; KETTLE, Jason, Grant; BAGAL, Sharanjeet, Kaur; BOYD, Scott; EATHERTON, Andrew, John; FILLERY, Shaun, Michael; ROBB, Graeme, Richard; RAUBO, Piotr, Antoni; (144 pag.)WO2018/206539; (2018); 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.889958-14-9,1-Boc-2-oxopiperazine,as a common compound, the synthetic route is as follows.

EXAMPLE 23 t-Butyl 3-oxo-2-phenylthio-1-piperazinecarboxylate (23) To a solution of dry diisopropylamine (0.31 ml, 2.2 mmole) and dry THF (2 ml) at 0 C. under argon is added dropwise, a hexane solution of n-butyllithium (0.90 ml, 2.2 mmole). After 1/2 hour of stirring a solution of 2 (0.200 g, 1.00 mmole) in 5 ml of dry THF is added dropwise and stirring continued for 3 hours. A solution of diphenyldisulfide (0.240 g, 1.10 mmole) in dry THF was added dropwise and the mixture is stirred for 1 hour at 0 C. before being allowed to warm to room temperature. Stirring is continued overnight and the reaction is quenched into ether/water and the aqueous phase extracted twice with ether. The ethereal extracts are washed with brine and dried over Na2 SO4, and the solvent is evaporated. The resulting yellow oil was chromatographed with 50% ethylacetate/chloroform and triturated with ether to afford 0.180 g (59%) of colorless solid 23. M.p. 138- 140 C. Alternatively, the phenyl ester of benzenesulfonothioic acid may be employed in place of diphenyldisulfide to prepare 23., 889958-14-9

The synthetic route of 889958-14-9 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Richardson-Merrell Inc.; US4341698; (1982); A;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

27561-62-2, Cyclohexyl(piperazin-1-yl)methanone is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

General procedure: The mixture of compound 3 (1g, 4.6mmol) and 95% ethanol (30ml) was added to morpholine (0.4g, 4.6mmol).The mixture was stirred at room temperature for 30min, then warmed up to 60C. After the starting 3 was completely consumed (the reaction courses was monitored by TLC), evaporation of the ethanol, the crude yellow compound 4j was obtained and purified by preparative thin-layer chromatography over silica gel PF 254 (2mm, ethyl acetate: petroleum ether=1:1). Yield: 78%.

27561-62-2, 27561-62-2 Cyclohexyl(piperazin-1-yl)methanone 3437502, apiperazines compound, is more and more widely used in various fields.

Reference：
Article; Xu, Feng; Yang, Zhen-Zhen; Jiang, Jun-Rong; Pan, Wan-Gui; Yang, Xiao-Le; Wu, Jian-Yong; Zhu, Yan; Wang, John; Shou, Qi-Yang; Wu, Han-Gui; Bioorganic and Medicinal Chemistry Letters; vol. 26; 13; (2016); p. 3042 – 3047;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics