Heterocyclic Building Blocks-piperazine

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.5317-33-9,3-(4-Methylpiperazin-1-yl)propan-1-ol,as a common compound, the synthetic route is as follows.

5317-33-9, To a stirred suspension of the 4-(2-fluoro-4- nitrophenoxy)-6-methoxyquinolin-7-ol (Example 72, step D, 0.15 g, 0.454 mmol) in CH2Cl2 (4 mL) at room temperature under nitrogen was added the 3-(4-methylpiperazin-l-yl)propan-l-ol (0.086 g, 0.545 mmol) followed by PPh3 (0.191 g, 0.727 mmol) and (E)-diethyl diazene-1,2- dicarboxylate (0.127 g, 0.727 mmol). After 17 hours stirring, the reaction was concentrated to a residue under reduced pressure. The crude was purified by silica gel flash column chromatography (10% MeOH in CH2Cl2) to afford 0.185 mg (87%) of the desired product. LRMS (ESI pos) m/e 471 (M+l).

The synthetic route of 5317-33-9 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; ARRAY BIOPHARMA INC.; GENENTECH, INC.; WO2007/146824; (2007); A2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

170911-92-9, tert-Butyl 4-(4-aminophenyl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To a stirred solution of 184 3-(2,6-dichlorophenyl)-2-methyl-7-methylsulfanyl-2H-pyrimido[5,4-e][1,3]oxazin-4-one (100 mg, 0.290 mmol, 1.0 eq) in 24 toluene (10 mL) was added 25 m-CPBA (100 mg, 0.58 mmol, 2.0 eq) and allowed to stir at rt for 30 min. 66 Tert-butyl 4-(4-aminophenyl) piperazine-1-carboxylate (107 mg, 0.35 mmol, 1.10 eq) and 27 DIPEA (149 mg, 1.16 mmol, and 4.0 eq) were added and allowed to stir at rt for 1 h. Progress of reaction was monitored by LCMS. After completion of reaction, solvent was removed under reduced pressure. Crude residue was suspended in 20 mL of 7 water, extracted with ethyl acetate (50 mL×2). Combined organic layer was washed with water (20 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. Crude residue was purified by flash chromatography using 19 ethyl acetate: 20 hexane to obtain 185 tert-butyl 4-[4-[[3-(2,6-dichlorophenyl)-2-methyl-4-oxo-2H-pyrimido[5,4-e][1,3]oxazin-7-yl]amino]phenyl]piperazine-1-carboxylate (100 mg, 59.1%). (0326) LCMS: 585 [M+1]+

170911-92-9, The synthetic route of 170911-92-9 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; giraFpharma LLC; Chakravarty, Sarvajit; PHAM, Son Minh; Kankanala, Jayakanth; AGARWAL, Anil Kumar; PUJALA, Brahmam; SONI, Sanjeev; ARYA, Satish K.; PALVE, Deepak; KUMAR, Varun; (360 pag.)US2019/106436; (2019); A1;,
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30459-17-7, 1-(4-Trifluoromethylphenyl)piperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

A solution of 5-methyl-3-isoxazole-4-carbonyl chloride (1.19g, 5.37mmol) in dioxane (15ml, anhydrous) was added dropwise to a cooled mixture (0C) containing l-(4-trifluoro- methylphenyl)-piperazine (1.24g, 5.38mmol commercially available) and pyridine (0.81ml, O.Olmol) in dioxane (25ml, anhydrous). The reaction solution was allowed to attain ambient temperature. Water was added to the solution affording a precipitation that was isolated by filtration. Re-crystallization from a mixture of MeOH/Acetonitrile (2: 1) afforded white crystalline compound (1.74g, 75%). 1H-NMR (400 MHz, DMSO-d6) delta 7.61-7.60 (m, 2H), 7.49-51 (m, 5H), 7.01-6.99 (m, 2H), 3.75 (br, 2H), 3.32 (br, 4H), 2.94 (br, 2H), 2.48 (s, 3H). 13C-NMR (400 MHz, DMSO-d6) delta 169.6(s), 162.4(s), 160.5(s), 153.6(s), 131.0(d), 129.8(d, 2H), 129.1(s), 128.2(d, 2C), 127.0 (q, 4JCF = 3.7 Hz, CCF3, 2C), 125.8 (q, lJ CF = 270.1 Hz, CCF3), 119.6 (q, 2JCF = 32.0 Hz, CCF3),115.4(d, 2C), 112.0(s), 48.0 (t, 4CH2), 12.1(q).

30459-17-7, The synthetic route of 30459-17-7 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; VIRONOVA AB; HOMMAN, Mohammed; KINGI, Ngarita; BERGMAN, Jan; ENGQVIST, Robert; WO2013/171334; (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.192130-34-0,tert-Butyl 4-(2-aminoethyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

To compound 4 (183mg , 0.8 mmol) in DCM (3 ml), was added DIPEA ( 0.278 ml, 2 eq) and then propionyl chloride (130mg, 1 mmol) . The reaction was stirred at room temperature for lhr. The mixture was concentrated and partitioned between ethyl acetate and water, ethyl acetate layer was separated and dried, concentrated, then HC1 in dioxane ( 4N, 2 ml) was added. The mixture was stirred at room temperature for lhr, concentrated to afford crude 5a. It was then diluted with dry DMF ( 5 ml), was added, followed by addition of DIPEA (0.278ml, 1.6 mmol) and then (Biotin-LC-LC-NHS ( 454mg, O.Smmol). The mixture was stirred at room temperature for 12 hrs. The mixture was diluted with water, extracted with ethyl acetate. The organics were concentrated and then purified by HPLC to yield the desired product 6a ( 390 mg). NMR: pass, 192130-34-0

The synthetic route of 192130-34-0 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; NESTEC S.A.; SELVARAJ, Fabiyola; PRINCEN, Fred; SINGH, Sharat; WO2014/188377; (2014); A2;,
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.262368-30-9,N-(4-Aminophenyl)-N-methyl-2-(4-methylpiperazin-1-yl)acetamide,as a common compound, the synthetic route is as follows.

To a stirred solution of methyl 2-oxo-2,3-dihydro-lH-pyrrolo[3,2- b]pyridine-6-carboxylate (0.18 g, 0.9366 mmol) in acetic anhydride (4 ml) was added triethyl orthobenzoate (0.630 g, 2.8098 mmol) at RT and the mixture was refluxed for 3 h at 110 C. The reaction mixture was evaporated and the resulting residue was used as such into next step without purification. [000163] Step-2: To a stirred solution of product from step-1 (0.18 g) in DMF (4 ml) was added N-(4-aminophenyl)-N-methyl-2-(4-methylpiperazin-l-yl)acetamide (0.180 g, 0.6861 mmol) at RT and the reaction mixture was heated at 110 C for 1 h. The reaction mixture was cooled to RT and stirred with triethyl amine (1 ml) for half an hour. The reaction mixture was evaporated and the crude product was purified by column chromatography using 0 to 10% methanol in dichloromethane as eluent to afford (Z)-methyl l-acetyl-3-((4-(N-methyl-2-(4- methylpiperazin- 1 -yl) acetamido)phenylamino)(phenyl)methylene)-2-oxo pyrrolo[3,2-b]pyridine-6-carboxylate as yellow solid. MS (ES+): m/z 583.4 (MH+).

262368-30-9, As the paragraph descriping shows that 262368-30-9 is playing an increasingly important role.

Reference：
Patent; ANGION BIOMEDICA CORP.; PANICKER, Bijoy; MISHRA, Rama, K.; JUNG, Dawoon; OEHLEN, Lambertus, J.W.M.; LIM, Dong, Sung; WO2013/112959; (2013); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

129799-08-2, 1-tert-Butyl 3-methyl piperazine-1,3-dicarboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To a solution of Intermediate 2 (1.0 g, 4.1 mmol) in anhydrous dichloromethane (40 mL) was added triethylamine (0.82 mL, 5.9 mmol) and 3-methoxy-4-tert-butylbenzoyl chloride* (1.11 g, 4.9 mmol). The resultant mixture was stirred at ambient temperature for 18 hours and washed with water. The organic phase was separated and evaporated to a gum, then purified by chromatography over silica gel using cyclohexane-ethyl acetate (4: 1, 3: 1 and then 2: 1 v/v) as eluent. The fractions containing the desired product were combined and evaporated to give the title compound as an amorphous solid. MS calcd for (C23H34N206 + H) + : 435. Found: (M+H) + = 435. * Prepared from 3-methoxy-4-tert-butylbenzoic acid (J. Org. Chem. (1961) 26,1732) using thionyl chloride., 129799-08-2

129799-08-2 1-tert-Butyl 3-methyl piperazine-1,3-dicarboxylate 2756819, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; GLAXO GROUP LIMITED; WO2005/79799; (2005); 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.

Compound 1 A mixture of Intermediate 1 (100 mg, 0.33 mmol), 2-methoxy-4-(4-methylpiperazin-l- yl)aniline (73 mg, 0.33 mmol),, and DIPEA (0.08 ml, 0.49 mmol) in DMSO (5 ml) was stirred at room temperature for 30 min. After checking the TLC, the mixture was added to water (100ml). After cooled with ice-bath, the solids were collected by filtration, washed by water. The crude product was purified by column chromatography (silica gel, 0-15% MeOH in DCM) to give the desired product as yellow solids (64 mg, 40% yield). 1H NMR (400 MHz, DMSO-de) delta 11.34 (br, 1H), 9.45 (br s, 1H), 8.15 (s, 1H), 7.13 (m, 2H), 6.93 (m, 1H), 6.65 (m, 1H), 6.50 (m, 1H), 6.23 (s, 1H), 3.77 (s, 3H), 3.18 (m, 4H), 2.46 (m, 4H), 2.39 (s, 3H), 2.23 (s, 3H); ESI-MS: calcd for C26H26FN702 487, found 488 (MH+). HPLC: retention time: 18.63 min. purity: 96%., 122833-04-9

The synthetic route of 122833-04-9 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; NANTBIOSCIENCE, INC.; TAO, Chunlin; POLAT,, Tulay; WEINGARTEN, Paul; NALLAN, Laxman; ARP, Forrest; WANG, Qinwei; HO, David; (129 pag.)WO2016/138527; (2016); 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.169447-70-5,(S)-tert-Butyl 2-methylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

A solution of 2-bromo-5-fluoropyridine (3.52 g, 20 mmol), (S)-tert-butyl 2- methylpiperazine-1-carboxylate (2 g, 11.36 mmol), t-BuONa (1.922 g, 20 mmol), BINAP (623 mg, 1 mmol), and Pd2(dba)3 (458 mg, 0.5 mmol) in dry toluene (20 mL) was stirred under N2 at 80 C for 16 h. The reaction mixture was concentrated and the mixture was purified by chromatography (silica, EtOAc/PE =1/10) to afford (S)-tert-butyl 4-(5-fluoropyridin-2-yl)-2- methylpiperazine-1-carboxylate (2.9 g, 9.82 mmol, 86%) as a yellow oil. ESI-MS (EI, m/z):296.2 [M+H]., 169447-70-5

The synthetic route of 169447-70-5 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; NAVITOR PHARMACEUTICALS, INC.; O’NEILL, David John; SAIAH, Eddine; KANG, Seong Woo Anthony; BREARLEY, Andrew; BENTLEY, Jonathan; (565 pag.)WO2018/89433; (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.5271-27-2,1-Methyl-3-phenylpiperazine,as a common compound, the synthetic route is as follows.,5271-27-2

1-Methyl-3-phenylpiperazine (1.8 g; 0.01 mol) was dissolved in 50 dichloromethane. Triethylamine (1 ml; 0.07 mol) was added. Trifluoroacetic anhydride (2 ml) was added neat. The mixture was quenched with 10percent sodium carbonate. The organic layer was washed again with carbonate, dried and evaporated to an oil (2.5 g; 92 percent). TLC very pure. Chiral GC: 5.9/6.2 min.

As the paragraph descriping shows that 5271-27-2 is playing an increasingly important role.

Reference：
Patent; N.V. ORGANON; WO2007/144409; (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.13754-38-6,1-Benzoylpiperazine,as a common compound, the synthetic route is as follows.

General procedure: To a mixture of 1-benzoylpiperazine (1.0 eq) and potassium carbonate (2.0 eq) in dimethylformamide was added dropwise a solution of the corresponding substituted 9-bromo-9H-fluorene (1.0 eq) in dimethylformamide (The synthesis of 9-bromo-9H-fluorene derivatives is reported in supporting information). After stirring for 24 h at room temperature, solvent was removed and the crude residue was dissolved in diethyl ether, washed with brine, dried over magnesium sulfate,filtered and concentrated under vacuum. The residue was purified by flash chromatography as indicated in each case to afford the title compound. Reagents: 1-Benzoylpiperazine (0.16 mmol, 30 mg), potassium carbonate (0.31 mmol, 43 mg) and 9-bromo-2-octyl-9H-fluorene (0.16 mmol, 55 mg). The crude product was purified by flash chromatography (gradient, 100% petroleum ether to 100% ethyl acetate in 15 min) to afford a yellow oil (38 mg, 53%). TLC Rf: 0.10 (petroleum ether/ethyl acetate 90/10). IR (cm-1): 697, 708, 740, 765, 828, 1001, 1015, 1141, 1154, 1255, 1277, 1302, 1425, 1455, 1634, 1715, 2853, 2923. HPLC: method 2, rt = 7.63 min, purity 97%. 1H NMR (300 MHz, CDCl3) delta (ppm): 0.82-1.01 (m, 3H); 1.23-1.47 (m, 10H); 1.59-1.78 (m, 2H); 2.43 (s, 2H); 2.72 (t, J = 7.8 Hz, 2H); 2.92 (s, 2H); 3.38 (s, 2H); 3.85 (s, 2H); 4.88 (s, 1H); 7.23 (d, J = 7.8 Hz, 1H); 7.30 (td, J = 1.5 Hz, 7.5 Hz, 1H); 7.34-7.43 (m, 6H); 7.47 (s, 1H); 7.61 (d, J = 7.5 Hz, 1H); 7.63 (d, J = 7.5 Hz, 1H); 7.67 (d, J = 7.1 Hz, 1H). 13C NMR (75 MHz, CDCl3) delta (ppm): 14.2 (CH3); 22.7 (CH2); 29.3 (CH2); 29.4 (CH2); 29.5 (CH2); 31.8 (CH2); 31.9 (CH2); 36.2 (CH2); 43.0 (CH2); 48.4 (CH2); 48.5 (CH2); 49.7 (CH2); 69.9 (CH); 119.5 (CH); 119.6 (CH); 125.8 (CH); 125.9 (CH); 126.7 (CH); 127.1 (2 * CH); 128.3 (CH); 128.4 (2 * CH); 128.5 (CH); 129.6 (CH); 135.9 (C); 138.7 (C); 141.2 (C); 142.4 (C); 143.3 (C); 143.6 (C); 170.3 (C). MS (DCI/CH4) m/z: 467.31 [M+H+], 277.20 [M-189]. HRMS (DCI/CH4): for C32H39N2O [M+H+]: calcd: 467.3062; found: 467.3063.

13754-38-6, 13754-38-6 1-Benzoylpiperazine 762654, apiperazines compound, is more and more widely used in various fields.

Reference：
Article; Chollet, Aurelien; Mori, Giorgia; Menendez, Christophe; Rodriguez, Frederic; Fabing, Isabelle; Pasca, Maria Rosalia; Madacki, Jan; Kordulakova, Jana; Constant, Patricia; Quemard, Annaik; Bernardes-Genisson, Vania; Lherbet, Christian; Baltas, Michel; European Journal of Medicinal Chemistry; vol. 101; (2015); p. 218 – 235;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics