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, Di- tert-butyl azodicarboxylate (0.478 g, 2.08 mmol) was added portionwise to a mixture of 4-chloro-7-hydroxy-6-methoxyquinazoline (0.350 g, 1.66 mmol), 3-(4-methyl-piperazin-1-yl)-propan-1-ol (Intermediate 7, 0.276 g, 1.74mmol), and triphenylphosphine (0.544 g, 2.08 mmol) in dichloromethane (20 mL) at r.t.. If necessary, further alcoholwas added. After stirring for 2 h, the solution was concentrated to 10 mL, mounted on silica and chromatographed(gradient, dichloromethane to dichloromethane : methanol = 3:2 within 1 h) to obtain 4-chloro-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazoline (brownish solid, 0.431 g, 1.23 mmol, 74 %). LC/ESI-MS: m/ z = 351 [M(35Cl) +H]+;Rt = 1.88 min. Cf. also WO 04/043472, page 32.

5317-33-9 3-(4-Methylpiperazin-1-yl)propan-1-ol 79208, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; 4SC AG; EP1674467; (2006); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

68104-63-2, 4-(Piperazin-1-yl)benzonitrile is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

68104-63-2, To a solution of 6.1 mmol 2-iodo-5-methanesulfonyl-benzoic acid in 20 ml dimethyl formamide were added successively 6.75 mmol TBTU, 43 mmol N-ethyldiisopropylamine and 6.75 mmol 4-piperazin-1-yl-benzonitrile (commercially available, e.g. from Fluka). The reaction mixture was stirred at 20 C. for 1.5 h and then concentrated in vacuo. Addition of 200 ml water followed by filtration yielded the crude product which was recrystallized from methanol to afford the title compound as a white solid (yield 87%). MS (m/e): 495.9 (M+H+, 100%).

The synthetic route of 68104-63-2 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Jolidon, Synese; Narquizian, Robert; Norcross, Roger David; Pinard, Emmanuel; US2006/149062; (2006); A1;,
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Piperazines – an overview | ScienceDirect Topics

30459-17-7, 1-(4-Trifluoromethylphenyl)piperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

General procedure: To a solution of 4 (100 mg, 0.23 mmol) in acetonitrile (CH3CN, 10 mL) was added the corresponding arylpiperazine or phenylpiperidine (1.2 equiv) and potassium carbonate (6.0 equiv). The reaction mixture was stirred at reflux for 16 h. After cooling to ambient temperature, the reaction mixture was filtered through a Buchner funnel. After filtration the filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography using ethyl acetate/petroleum ether (1/5, v/v) as eluent to afford the corresponding products, and all compounds were recrystallized from trichloromethane and n-hexane.

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

Reference：
Article; Chen, Hong; Liang, Xue; Xu, Fang; Xu, Bingbing; He, Xuelan; Huang, Biyun; Yuan, Mu; Molecules; vol. 19; 8; (2014); p. 12048 – 12064;,
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.30459-17-7,1-(4-Trifluoromethylphenyl)piperazine,as a common compound, the synthetic route is as follows.

Valeric acid (106 ??, 0.979 mmol), HOBt (144 mg, 0.979 mmol), TBTU (343 mg, 0.979 mmol), anhydrous triethylamine (216 ??, 1 .56 mmol) and dry DMF (2 ml) were placed in an oven-dried Schlenk tube under a nitrogen atmosphere. The resulting solution was stirred at room temperature for 15 minutes. A second Schlenk tube was prepared containing 1-(4-trifluoromethyl phenyl) piperazine (246 mg, 1.07 mmol) and dry DMF (1 ml) under a nitrogen atmosphere. The resulting solution was stirred until complete dissolution of the piperazine had occurred. The piperazine solution was then transferred, via a cannula, to the first Schlenk tube containing the carboxylic acid. The resulting solution was stirred for 24 hrs, under nitrogen, and monitored by TLC. After 24 hrs, the DMF was removed under reduced pressure and the resulting oil was acidified using a 0.1 M hydrochloric acid solution. The aqueous mixture was extracted with dichloromethane (20 ml, followed by 4 x 10 ml) and the organic layer washed with a saturated sodium bicarbonate solution (3 x 20 ml) and brine (3 x 20 ml). The organic layer was dried over magnesium sulphate and evaporated under reduced pressure. The residue was purified using flash chromatography (3:2, EtOAc:n-hexane) to obtain the desired product in an 57 % yield. H NMR (300 MHz, CDCI3) ? 7.48 (d, 2H), 6.91 (d, 2H), 3.76 (t, 2H), 3.63 (t, 2H), 3.24-3.30 (m, 4H), 2.35 (t, 2H), 1.59-1.69 (m, 2H), 1 .33-1.45 (m, 2H), 0.92 (t, 3H). MS (+ESI) calcd for C16 H21 F3 N2 O m/z: [M + H]+ , 314.1596; found 315.1679 [Diff(ppm) = – 3.06]

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

Reference：
Patent; NATIONAL UNIVERSITY OF IRELAND, MAYNOOTH; STEPHENS, John; FINDLAY, John; KINSELLA, Gemma; MARTIN, Darren; DEVINE, Robert; VELASCO-TORRIJOS, Trinidad; WO2013/60860; (2013); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5308-25-8, 1-Ethylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

5308-25-8, To a solution of 1-ethylpiperazine (1 g, 8.771 mmol, 1.0 eq) in DMF were added K2CO3 (3 g, 21.927 mmol, 2.5 eq.) and ethyl 2-bromoacetate (2.19 g, 13.156 mmol, 1.5 eq.). The mixture was stirred at RT for 16 h. The mixture was quenched and extracted as in Intermediate Example 5(a). The solvent was distilled off to afford the product in 76.4% yield (1.3 g).

The synthetic route of 5308-25-8 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Linnanen, Tero; Wohlfahrt, Gerd; Nanduri, Srinivas; Ujjinamatada, Ravi; Rajagopalan, Srinivasan; Mukherjee, Subhendu; US2015/11548; (2015); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

509073-62-5, tert-Butyl 4-(4-nitrobenzoyl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,509073-62-5

To a degassed solution of tert-butyl 4-(4-nitrobenzoyl)piperazine-1-carboxylate (2c, 4.1 g, 12.3 mmol, 1 equiv.) in anhydrous MeOH (40 mL) was added Pd/C (10% wt., dry; 600 mg).The reaction was sealed, fifted with a H2 balloon and then stirred for 3 h at room temperature. The reaction mixture was filtered through Celite and then concentrated to obtain the product 2d as a white foam (3.7 g, 12 mmol, 98% yield).

The synthetic route of 509073-62-5 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; DANA-FARBER CANCER INSTITUTE, INC.; GRAY, Nathanael S.; DOBROVOLSKY, Dennis; HUANG, Hai-Tsang; (152 pag.)WO2018/98275; (2018); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

4318-42-7, 1-Isopropylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Step 2 [3-(1-Benzyl-piperidin-2-yl)-1H-indol-6-yl]-(4-isopropyl-piperazin-1-yl)-methanone A mixture of 1.25 g (4 mmol) 3-(1-benzyl-piperidin-2-yl)-1H-indole-6-carboxylic acid methyl ester and 0.2 g (4.8 mmol) LiOH.H2O in 40 mL water and 40 mL methanol was heated to reflux for 20 h. After 4 h additional 0.56 g LiOH.H2O and 30 mL water was added. After evaporation of the methanol the mixture was adjusted to pH=2 and evaporated to dryness. 25 mL DMF was added and together with 1.4 g (4 mmol) TBTU, 2.8 g (22 mmol) DIPEA and 0.55 g (4 mmol) 1-(2-propyl)-piperazine stirred at room temperature for 3 h. Isolute was added and after evaporation purified by column chromatography on silica eluding with a gradient formed from DCM/methanol/NH3 aq. The product fractions were evaporated to yield 1.14 g (71percent) of the title compound as light brown solid. MS (m/e): 445.3 (MH+)., 4318-42-7

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

Reference：
Patent; Nettekoven, Matthias; Roche, Olivier; US2008/32976; (2008); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

13484-40-7, 1-(2-Methoxyethyl)piperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

2-Chloro-IJ-{ 3- [5-fluoro-3- (4-methoxyphenyl) -4- oxo-8-propoxy-4H-quinolin-l-yl] propyl} acetamide (370 mg, 0.8 mmol) was suspended in acetonitrile (12 ml) . l-(2- Methoxyethyl)piperazine (138 mg, 0.96 mmol), triethylamine (162 mg, 1.6 mmol) and acetonitrile (2 ml) were added to the suspension, and stirred at 70 to 8O0C for 6 hours. The resulting mixture was concentrated under reduced pressure, and the residue was subjected to extraction using ethyl acetate. The extract was then sequentially washed with water, an aqueous saturated sodium chloride solution, and an aqueous saturated sodium bicarbonate solution. The washed product was concentrated under reduced pressure, and the residue was purified using silica gel column chromatography (dichloromethane : methanol = 30 : 1 ? 10 : 1) . The purified product was concentrated under reduced pressure, and the residue was then dissolved in ethyl acetate (5 ml) . A 4N hydrogen chloride ethyl acetate solution (0.19 ml) was added thereto and stirred, and then the mixture was concentrated to dryness under reduced pressure, giving a pale yellow amorphous solid of N-{ 3- [5-fluoro-3- (4-methoxyphenyl) -A- oxo-8-propoxy-4H-quinolin-l-yl] propyl} -2- [4- (2- methoxyethyl) piperazin-1-yl] acetamide hydrochloride (200 mg) .1H-NMR (DMSO-d6) deltappm: 1.00 (3H, t, J=7.3 Hz), 1.78-1.89 (4H, m) , 2.50-3.00 (4H, m) , 2.96-3.20 (8H, m) , 3.25 (3H, s), 3.62-3.66 (4H, m) , 3.75 (3H, s) , 3.98-4.04 (2H, m) , 4.56 (2H, t, J=6.4 Hz), 6.91-7.02 (3H, m) , 7.24 (IH, dd, J=4.5 Hz, 9.1 Hz), 7.60 (2H, d, J=8.8 Hz), 8.00 (IH, s) , 8.07 (IH, brs) .

13484-40-7, As the paragraph descriping shows that 13484-40-7 is playing an increasingly important role.

Reference：
Patent; OTSUKA PHARMACEUTICAL CO., LTD.; OTSUBO, Kenji; YAMAUCHI, Takahito; OCHI, Yuji; WO2010/64735; (2010); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

197638-83-8, 1-Boc-4-(4-Formylphenyl)piperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To a mixture of 5-bromo-4-(4-((2-methylthiazol-4-yl)methyl)piperazin-1-yl)-3-nitropyridin-2-amine (0.062 g, 0.15 mmol) in EtOH (2.6 mL) and DMF (0.35 mL), tert-butyl 4-(4-formylphenyl)piperazine-1-carboxylate (0.044 g, 0.165 mmol) was added followed by a freshly prepared aqueous solution of Na2S2O4 (1M; 0.45 mL, 0.45 mmol). The reaction mixture was heated at 85 C. for 24 h, then allowed to cool to room temperature and diluted with DCM and a few drops of aqueous NH3 until complete dissolution was observed. This solution was deposited on two preparative silica TLC plates and eluted with DCM/MeOH (v/v 96:4) to give the title compound as a off-white solid (0.043 g, 47%); 1H-NMR (500 Mz, DMSO-d6): delta 1.43 (s, 9H, C(CH3)3), 2.61-2.70 (m, 7H), 3.22-3.31 (m, 4H), 3.43-3.52 (m, 4H), 3.60-3.68 (m, 6H), 7.07 (d, J=9.0 Hz, 2H, ArH, C6H4), 7.32 (s, 1H, thiazole 5-H), 8.04 (d, J=8.5 Hz, 2H, ArH, C6H4), 8.23 (s, 1H, imidazo[4,5-b]pyridine 5-H), 13.22 (br s, 1H, imidazo[4,5-b]pyridine N-H); LC (Method B)-MS (ESI, m/z) 4.01 min-653/655 [(M+H)+, Br isotopic pattern]. ESI-HRMS: Found: 653.2022, calculated for C30H38BrN8O2S (M+H)+: 653.2019.

197638-83-8, As the paragraph descriping shows that 197638-83-8 is playing an increasingly important role.

Reference：
Patent; THE INSTITUTE OF CANCER RESEARCH; US2009/247507; (2009); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

13889-98-0, 1-Acetylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

3-Bromo-l-propanol (1.1 g, 7.8 mmol) and NaHCO3 (0.66 g, 7.8 mmol) were added sequentially to a mixture of 1-acetylpiperazine (1.0 g, 7.8 mmol) in DCM (10 mL) at 4O0C. The reaction mixture was stirred at 4O0C for 4 h and then stirred at rt for 24 h. DCM, a saturated aq. solution OfNaHCO3 and brine were added and the layers were separated. The organic layer was dried (phase separator) and concentrated in vacuo to give the title compound (0.67 g, 46%). 1U NMR (400 MHz, CDCl3) delta 3.82-3.74 (m, 2H), 3.64-3.56 (m, 2H), 3.48-3.42 (m, 2H), 2.64-2.58 (m, 2H), 2.52-2.44 (m, 4H), 2.06 (s, 3H), 1.76-1.68 (m, 2H)., 13889-98-0

The synthetic route of 13889-98-0 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; ASTRAZENECA AB; WO2009/82346; (2009); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics