Heterocyclic Building Blocks-piperazine

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.934-98-5,2-(4-Methylpiperazin-1-yl)ethanamine,as a common compound, the synthetic route is as follows.,934-98-5

General procedure: To a solution of 6-amino-4-anilinoquinazoline or 4-(1-phenylethyl)quinazoline-4,6-diamine (0.23 mmol) in acetonitrile(5 mL), CDI (0.11 g, 0.69 mmol) was added. The reaction mixture was stirred at room temperature for 8 h when lots of solidproduced. To this suspension, the solution of 2-(4-methylpiperazin-1-yl)ethylamine in 5 mL of acetonitrile was added. Then, the mixture was stirred at room temperature for 2 h, refluxed for another 2 h, cooled to room temperature and concentrated under reduced pressure. The residue was added water (20 mL) and the mixture was extracted with dichloromethane (20 mL 3). The organic layer was combined, washed with brine (20 mL), dried(Na2SO4), concentrated under reduced pressure and purified bychromatography on silica gel (dichloromethane/methanol = 15:1,v/v) to give compounds 4a or 4b as yellow powder. 4.1.60. 1-(2-(4-Methylpiperazin-1-yl)ethyl)-3-(4-((3-(trifluoromethyl)phenyl)amino)quinazolin-6-yl)urea (4a)Yield 45.5percent. Mp: 169.8?170.5 C. 1H NMR (DMSO-d6): d 9.96 (s,1H, N-H), 9.03 (s, 1H, N-H), 8.54 (s, 1H, N-H), 8.46 (d, 1H, Ar-H,J = 2.0 Hz), 8.29 (s, 1H, Ar-H), 8.21 (d, 1H, Ar-H, J = 8.0 Hz), 7.83(dd, 1H, Ar-H, J1 = 2.0 Hz, J2 = 8.8 Hz), 7.74 (d, 1H, Ar-H,J = 8.8 Hz), 7.62 (t, 1H, Ar-H, J = 8.0 Hz), 7.44 (d, 1H, Ar-H,J = 7.6 Hz), 6.35 (t, 1H, Ar-H, J = 5.2 Hz), 3.20?3.29 (m, 4H,2 CH2), 2.41?2.49 (m, 8H, 4 N-CH2), 2.27 (s, 3H, N-CH3). 13CNMR (DMSO-d6): d 157.4, 155.6, 152.5, 145.9, 141.0, 139.2, 130.0,129.5, 128.8, 126.7, 124.7 (d, JC?F = 261 Hz), 126.0, 119.8, 118.4,116.2, 109.3, 57.6, 54.7 (2 CH2), 52.4 (2 CH2), 45.5, 36.9. ESIHRMSm/z: calcd for C23H27F3N7O [M+H]+: 474.2229; found:474.2224.

The synthetic route of 934-98-5 has been constantly updated, and we look forward to future research findings.

Reference：
Article; Zuo, Sai-Jie; Zhang, Sai; Mao, Shuai; Xie, Xiao-Xiao; Xiao, Xue; Xin, Min-Hnag; Xuan, Wei; He, Yuan-Yuan; Cao, Yong-Xiao; Zhang, San-Qi; Bioorganic and Medicinal Chemistry; vol. 24; 2; (2016); p. 179 – 190;,
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With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.639068-43-2,tert-Butyl 3,5-dimethylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

639068-43-2, General procedure: To a stirred solution of compound 13a-b, 17a-b (1.0 mmol) inCH3CN (20 mL) were added N-Boc-piperazine (180.9 mg,0.9 mmol), K2CO3 (205.9 mg, 1.5 mmol), KI (166.0 mg, 1.0 mmol)and 18-crown-6 (26.4 mg, 0.1 mmol) at room temperature. Themixture was stirred overnight at 80 C and filtered. The filtrate wasdiluted by DCM and washed by brine. The organic layer was concentrated for next step. To a stirred solution of the abovecompounds in DCM (20 mL) was added TFA (3 mL) at room temperature.The mixture was stirred for 3e4 h and concentrated toafford the crude products 15a-o and 19a-f in a yield of 35%e42%. Toa stirred solution of above crudes in anhydrous MeOH (10 mL) wasadded BTZ core compound 11 (403.2 mg, 1.0 mmol) and Et3N(0.2 mL, 1.5 mmolj) at room temperature. The mixture was stirredfor 1e3 h at 40 C and concentrated. The residue was purified bysilica gel column (DCM: MeOH 20: 1) to give 1a-f and 2a-e (25%e41% for two steps).

639068-43-2 tert-Butyl 3,5-dimethylpiperazine-1-carboxylate 22219990, apiperazines compound, is more and more widely used in various fields.

Reference：
Article; Wang, Apeng; Lv, Kai; Tao, Zeyu; Gu, Jian; Fu, Lei; Liu, Mingliang; Wan, Baojie; Franzblau, Scott G.; Ma, Chao; Ma, Xican; Han, Bing; Wang, Aoyu; Xu, Shijie; Lu, Yu; European Journal of Medicinal Chemistry; vol. 181; (2019);,
Piperazine – Wikipedia
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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.

To a solution of l-(2-hydroxyethyl)piperazine (51.7 g, 398 mmol) in DCM (500 mL) was added NEt3 (70.0 mL, 526 mmol) and dicarbonate (80.0 g, 367 mmol). The reaction mixture was stirred overnight at r.t. and then washed with IM aq Na2CO3 solution (2 x 300 mL). The organic phase was dried (MgSO4) and concentrated in vacuo to give tert-bvXy 4-(2-hydroxyethyl)piperazine-l-carboxylate (66.0 g, 72%) as a colourless oil.

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

Reference：
Patent; BIOVITRUM AB (publ); WO2009/147221; (2009); A1;,
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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.

2-Methoxy-4-(4-methylpyridazin-1-yl)phenylamine (2.21 g, 1.0 eq) was added to compound l-1 (3.7 g, 1. Oeq) n-butanol (70 ml) In the solution, the reaction was carried out at 90 C for 2-3 hours. After the reaction was completed by TLC, the mixture was cooled to room temperature, filtered, washed and dried to give a red solid (4.6 g)., 122833-04-9

As the paragraph descriping shows that 122833-04-9 is playing an increasingly important role.

Reference：
Patent; Chengdu University; Zhao Lifeng; Gou Xiaojun; (47 pag.)CN109384788; (2019); A;,
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934-98-5, 2-(4-Methylpiperazin-1-yl)ethanamine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

934-98-5, The dichloropyrimidine (3.29 gm, 0.01 moles) was dissolved in n-butanol (30 mL) and N-methyl-N’-(2-aminoethyl)piperazine (3.0 gm, 2.1 X 10″2 moles) was added. This mixture was heated to 1 15°C. forming a dark orange solution. After 2 hours, TLC (silica, 25percent methanol in methylene chloride) showed some remaining starting material along with a single product. Diisopropylethylamine (02.58 gm, 0.02 moles) was added along with additional N-methyl-N’- (2-aminoethyl)piperazine (1.0 gm, 7.0 X 10″3 moles) and this solution was heated at 1 15°C. for an additional 2 hours. After cooling the reaction was diluted with hexane (100 mL) and this solution was extracted with water (50 mL). The hexane solution was dried over magnesium sulfate, filtered and the solvents were removed under reduced pressure. The remaining orange solid was boiled in hexane (50 mL) and then cooled on ice. The solid was isolated by filtration, washed with hexane and dried. Yield was 3.0 gm, (55percent).

The synthetic route of 934-98-5 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; JANUS BIOTHERAPEUTICS, INC.; LIPFORD, Grayson, B.; ZEPP, Charles, M.; WO2012/167053; (2012); A1;,
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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.

In a 25 mL round bottom flask was added 100 mg (0.22 mmol) of Intermediate 4, 59.8 mg (0.26 mmol) of 1-(4-trifluoromethylphenyl)piperazine, 182 mg (1.32 mmol) of potassium carbonate, 15 mL of acetonitrile,The reaction was carried out at 86[deg.] C. for 16 h. TLC showed that the starting material was completely reacted. Stop the reaction, filter, and concentrate. The crude product was purified by column chromatography on silica gel, eluent: V (ethyl acetate): V (petroleum ether) = 1:3 to give 35.2 mg of a white solid. Yield: 33%.

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

Reference：
Patent; Yuan Mu; Chen Hong; Ye Bibo; Yang Zonglin; (17 pag.)CN107573302; (2018); A;,
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Piperazines – an overview | ScienceDirect Topics

59702-31-7, 1-Ethylpiperazine-2,3-dione is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

500 ml of ethylene glycol dimethyl ether and 28.4 g of 4-ethyl-2,3-bisperoxazine were sequentially added to a 1 L three-necked flask, and the mixture was evenly stirred. 4.6 g of sodium metal was added and the mixture was heated to reflux for 10 hours.Cooled to 5 C,Stirring in batches by adding a good configuration of the triphosgene solution,The reaction temperature was controlled not to exceed 10 C,Adding filtrate to remove the activated carbon, filter to remove activated carbon, the filtrate vacuum drying, drying, in a white solid, that is, N, N, N-dimethylformamide, N, N-dimethylformamide, Carbonyl-bis- (4-ethyl-2,3-bisperoxypyrazine) was obtained The preparation method was the same as that of Example 1 except that the reaction temperature of sodium bisoxypiperazine and triphosgene was -15 C, and the obtained N, N’-carbonyl-bis- (4-ethyl- Piperazine)The yield of 4-ethyl-2,3-bisperoxypiperazine was 95%. The purity was 98.5% by HPLC., 59702-31-7

59702-31-7 1-Ethylpiperazine-2,3-dione 108812, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; Shandong Ai Fu Special Technology Co., Ltd.; Gao, Aihong; Feng, Weichun; Zhang, Jianwen; Ji, Xiaohong; Liu, Lixiu; Liu, Maoling; Wang, Liqin; (6 pag.)CN105524001; (2016); A;,
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3022-15-9, Piperazine-2-carboxylic acid dihydrochloride is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To a solution of piperazine-2-carboxylic acid dihydrochloride (25.0 g, 123 mmol), dioxane (180 ml) and 5N aqueous sodium hydroxide solution (90 ml) was added dropwise di-tert-butyl dicarbonate (62.7 g, 288 mmol) under ice-cooling. The mixture was stirred at room temperature for 4 hr, and the solvent was evaporated under reduced pressure. The residue was washed with ether, and acidified to pH=2-3 with concentrated hydrochloric acid under ice-cooling, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to give the object product (31.5 g, 77.6%) as a solid. 1H-NMR (CDCl3) delta; 1.44 (18H, s), 2.87 (1H, br s), 3.08-3.23 (2H, m), 3.76-4.10 (2H, m), 4.51-4.75 (2H, m), 5.07 (1H, br s).

3022-15-9, 3022-15-9 Piperazine-2-carboxylic acid dihydrochloride 2723757, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; Matsumoto, Takahiro; Kamo, Izumi; Nomura, Izumi; US2009/318412; (2009); A1;,
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Piperazines – an overview | ScienceDirect Topics

50606-32-1, Butyl piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,50606-32-1

2-{[Methyl(5,6,7,8-tetrahydro-8-quinolinyl)amino]methyl}-1H-benzimidazole-4-carbaldehyde (100 mg, 0.30 mmol), /V-butoxycarbonylpiperizine (115 mg, 0.60mmol), acetic acid (28 mg, 0.47 mmol) and sodium triacetoxyborohydride (100 mg,0.47 mmol) were dissolved in 1,2-dichloroethane (10 ml_) and stirred for 16 h at roomtemperature. The reaction concentrated and purified using reverse phase HPLC (0%to 70% acetonitrile/water/0.1% trifluoroacetic acid gradient) to provide the protectedamine. The carbamate was dissolved in dichloromethane (2 ml_) and trifluoroaceticacid (2 ml) and stirred for 3 h at room temperature. The reaction was concentrated,dissolved in water and lyophilized to provide the product (68 mg, 30%) as an off-white solid: 1H-NMR (DMSO-d6) 5 8.62 (d, 1H), 7.94 (d, 1H), 7.72 (d, 1H), 7.58-7.54(m, 1H), 7.41-7.35 (m, 2H), 4.74-4.70 (m, 1H), 4.60 (d, 1H), 4.48 (d, 1H), 4.38 (s,2H), 3.25 (br s, 4H), 3.13 (br s, 4H), 2.88-2.80 (m, 2H), 2.65 (s, 3H), 2.36-2.30 (m,1 H), 2.08-1.96 (m, 2H), 1.82-1.72 (m, 1 H). MS m/z 391 (M+1).

As the paragraph descriping shows that 50606-32-1 is playing an increasingly important role.

Reference：
Patent; SMITHKLINE BEECHAM CORPORATION; WO2006/23400; (2006); A2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

342405-34-9, 4-(4-Methylpiperazino)benzyl Alcohol is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To a solution of (4-(4-methylpiperazin-1-yl)phenyl)methanol (103 mg, 0.499 mmol), DIEA (0.131 mL, 0.749 mmol), and DMAP (6.10 mg, 0.050 mmol) in dichloromethane (2.5 mL) at 20 C was added methanesulfonyl chloride (0.058 mL, 0.749 mmol). The reaction mixture was stirred at the same temp while progress was monitored by LCMS. After stirring 24 hours at 20 C, the reaction mixture was concentrated and the resulting material purified by normal phase chromatography (Biotage Isolera, 10 g SNAP ULTRA column, DCM/MeOH) to obtain 123 mg of a brown solid. A portion of this material (27 mg) in N,N- dimethylformamide (0.5 mL) was added to a suspension of 4-ethyl-2-mercapto-6-(4-methyl- 1,4-diazepan-1-yl)pyridine-3,5-dicarbonitrile (synthesis described in Example 69, step 1, 46 mg, 0.122 mmol) and Et3N (0.017 mL, 0.122 mmol) in N,N-dimethylformamide (0.5 mL) at 0 C The reaction mixture was then stirred at 0 C overnight. After stirring overnight at 0 C, the reaction mixture was warmed to room temperature. The reaction mixture was filtered. The filtrate was purified by reverse phase HPLC (Gilson, 30 mm x 50 mm Gemini Column, NH4OH modifier) then re-purified by reverse phase HPLC (Gilson, 30 mm x 50 mm Gemini Column, NH4OH modifier) to obtain 4-ethyl-2-(4-methyl-1,4-diazepan-1-yl)-6- ((4-(4-methylpiperazin-1-yl)benzyl)thio)pyridine-3,5-dicarbonitrile (6 mg) as a yellow oil LCMS m/z = 490.4 [M+H]+.1H NMR (400 MHz, METHANOL-d4) delta ppm 7.26-7.30 (m, J=8.62 Hz, 2H), 6.92-6.97 (m, 2H), 4.44 (s, 2H), 3.95-4.03 (m, 4H), 3.18-3.24 (m, 4H), 2.91 (q, J=7.60 Hz, 2H), 2.76-2.80 (m, 2H), 2.62-2.67 (m, 6H), 2.38 (s, 3H), 2.37 (s, 3H), 2.04-2.11 (m, 2H), 1.31 (t, J=7.60 Hz, 3H).

342405-34-9, The synthetic route of 342405-34-9 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; ADAMS, Nicholas David; BENOWITZ, Andrew B.; RUEDA BENEDE, Maria Lourdes; EVANS, Karen Anderson; FOSBENNER, David T.; KING, Bryan Wayne; LI, Mei; MILLER, William Henry; REIF, Alexander Joseph; ROMERIL, Stuart Paul; SCHMIDT, Stanley J.; WIGGALL, Kenneth; (1283 pag.)WO2017/216726; (2017); A1;,
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Piperazines – an overview | ScienceDirect Topics