Heterocyclic Building Blocks-piperazine

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.3022-15-9,Piperazine-2-carboxylic acid dihydrochloride,as a common compound, the synthetic route is as follows.

Intermediate 1 : 1 ,4-Bis{[(1 ,1 -Dimethylethyl)oxy]carbonyl}-2- piperazinecarboxylic acidTo a solution of 2-piperazinecarboxylic acid (10 g) dihydrochloride in methanol (500 mL) at 0 C was added triethylamine (28.8 mL) dropwise via a dropping funnel. After addition, the solution was stirred for 30 minutes and then cooled to 0 C before addition of di-tert-butyl dicarbonate (27.4 mL). The reaction was stirred for 18 h at room temperature. The reaction mixture was concentrated under vacuum and then partitioned between ethyl acetate (500 ml) and water (500 mL). The organic phase was washed with further water (500 mL) and then brine (300 mL) before it was dried (Na2S04), filtered and the solvent removed under vacuum to give an oil of 3g, which was discarded. The aqueous layer was acidified to pH 2 with 5M HCI and then extracted with ethyl acetate (2 x 700 mL). The organic phase was dried (Na2S04), filtered and the solvent removed under vacuum to give the title compound as a white solid (14.58 g).LCMS (low pH) RT 0.98 min : m/z (ES) 331 [M+H]+

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; CONVERGENCE PHARMACEUTICALS LIMITED; NORTON, David; ANDREOTTI, Daniele; WARD, Simon E; PROFETA, Roberto; SPADA, Simone; PRICE, Helen Susanne; WO2012/98400; (2012); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

129779-30-2, (3R,5S)-rel-tert-Butyl 3,5-dimethylpiperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

2-(lH-Indazol-4-ylV6-rf3R.5S)-4-(2-methoxy-ethylV3,5-dimethyl-piperazin-l- ylmethyl]-4-mophiholin-4-yl-thienof3,2-d]pyrimidine (98).Prepared via 2-Chloro-6-[(3R,5S)-4-(2-methoxy-ethyl)-3,5-dimethyl- piperazin- 1 -ylmethyl]-4-mophiholin-4-yl-thieno[3,2-d]pyrimidine, prepared from (2R,6S)- 1 -(2-methoxy-ethyl)-2,6-dimethyl-piperazine.Amine preparation: to a solution of 2,6-dimethylpiperazine (predominantly cis) (250mg), te?t-butanol (2.5mL), sodium hydroxide (88mg) and water (0.5mL) was added a solution of di-tert-butyl-dicarbonate (478mg) in tert-butanol (0.5mL). After stirring overnight, the reaction mixture was diluted with ethyl acetate, washed with brine, dried (MgSO4) and the solvent was removed in vacuo to yield (3R,5S)- 3,5-dimethyl-piperazine-l-carboxylic acid tert-butyl ester (400mg).A mixture of (3R,5S)-3,5-dimethyl-piperazine-l-carboxylic acid tert-butyl ester (1.5g), 2-bromoethyl methyl ether (1.32mL) and potassium carbonate (1.06g) was heated to 1200C in DMF (15mL) for 2 days. The reaction mixture was cooled, diluted with ethyl acetate, washed with brine, dried (MgSO4) and the solvent was removed in vacuo to liberate (3R,5S)-4-(2-methoxy-ethyl)-3,5-dimethyl-piperazine- 1-carboxylic acid tert-butyl ester (1.4g) after column chromatography.Removal of the BOC group with HCl yielded the desired compound, which was isolated as the hydrochloride salt. EPO -Sl-1H NMR (400MHz, CDCl3): 1.01 (6H, d), 1.9 (2H, m), 2.61 (4H, m), 2.82 (2H, t), 3.27 (3H, s), 3.37 (2H, t), 3.71 (2H, s), 3.85 (4H,m), 4.02 (4H,m), 7.3 (IH, s), 7.43 (IH, t), 7.51 (IH, d), 8.21 (IH, d), 8.95 (lH,s), 10.10 (IH, m); MS (ESf) 522.35 (MH+).

129779-30-2, The synthetic route of 129779-30-2 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; PIRAMED LIMITED; WO2006/46031; (2006); 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.5464-12-0,1-(2-Hydroxyethyl)-4-methylpiperazine,as a common compound, the synthetic route is as follows.

Example 12(5Z)-5-[(1-{[4-(Methyloxy)-2-(trifluoromethyl)phenyl]methyl}-1H-indazol-5-yl)methylidene]-3-[2-(4-methyl piperazin-1-yl)ethyl]-1,3-thiazolidine-2,4-dione (5Z)-5-[(1-{[4-(Methyloxy)-2-(trifluoromethyl)phenyl]methyl}-1H-indazol-5-yl)methylidene]-3-[2-(4-methylpiperazin-1-yl)ethyl]-1,3-thiazolidine-2,4-dione was prepared from [(5Z)-5-({1-[4-methoxy-2-(trifluoromethyl)benzyl]-1H-indazol-5-yl}methylidene)-2,4-dioxo-1,3-thiazolidine (from Example 8) and 2-(4-methylpiperazin-1-yl)ethanol following General Procedure J.1H NMR (400 MHz, CDCl3): delta 8.15 (d, 1H), 8.09 (m, 1H), 7.92 (s, 1H), 7.56 (dd, 1H), 7.29 (d, 1H), 7.22 (d, 1H), 6.86 (dd, 1H), 6.67 (d, 1H), 5.75 (s, 2H), 3.98 (br, 2H), 3.79 (s, 3H), 3.73 (br, 2H), 3.45 (br, 2H), 3.15 (t, 2H), 2.50 (br, 4H), 2.34 (s, 3H).LC/MS: mass calcd. for C17H28F3N5O3S: 559.19, found 560.3 [M+H]+ General Procedure J. To a mixture of 5-[1-(substituted benzyl)-1H-heteroar-5-ylmethylene]-1,3-thiazolidine-2,4-dione from Procedure E (0.25 mmol), an aliphatic alcohol (0.375 mmol) and Ph3P (0.375 mmol), in THF (2 mL) was added DIAD (0.375 mmol) and the solution was stirred at rt for 2 h. The reaction was concentrated in vacuo and the resultant residue was purified by silica gel chromatography (DCM/MeOH) to afford the desired 5-[1-(substituted benzyl)-1H-heteroar-5-ylmethylene]-(3-alkylated)-1,3-thiazolidine-2,4-dione product, 5464-12-0

Big data shows that 5464-12-0 is playing an increasingly important role.

Reference：
Patent; Bignan, Gilles; Cheung, Wing; Gaul, Micheal; Huang, Hui; Li, Xun; Patch, Raymond; Patel, Sharmila; Player, Mark; Xu, Guozhang; Zhao, Bao-Ping; Liu, Jian; US2011/294780; (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.154590-34-8,tert-Butyl 4-(2-fluoro-4-nitrophenyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

General procedure: To a solution of 1a (5 g, 22.5 mmol) in 95% ethanol (100 mL) wasadded goethite (FeO(OH))/C (1.0 g) at room temperature. And a solution of 80% hydrazine hydrate (25 mL, 400 mmol) in 95% ethanol (50 mL) was added dropwise to the mixture at 0 C. The reaction mixture was stirred at 80 C for 4 h. The solvent was removed in vacuo to give 2a (3.8 g, yield 74.5%). MS m/z: 278.2 [M+H]+., 154590-34-8

The synthetic route of 154590-34-8 has been constantly updated, and we look forward to future research findings.

Reference：
Article; Bao, Jiyin; Liu, Haichun; Zhi, Yanle; Yang, Wenqianzi; Zhang, Jiawei; Lu, Tao; Wang, Yue; Lu, Shuai; Bioorganic Chemistry; vol. 94; (2020);,
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

General procedure: In a 25 mL two-necked round bottomed flask benzoxazole (1.0 mmol), AcOH (2.0 mmol), amine (2.0 mmol), and NIS (0.05 mmol) were added. The cold aqueous solution of H2O2 (2.0 mmol) was slowly added to the above suspension followed by 5 mL acetonitrile. Then the above mixture was kept under stirring condition till the completion of reaction. The progress of the reaction was monitored using gas chromatography. After completion of reaction the reaction mixture was extracted with ethyl acetate and treated with saturated solution of Na2CO3. Then consecutive water washing was given to the organic layer. The organic layer was separated, dried over anhydrous sodium sulphate followed by removal of solvent under reduced pressure. The reaction mixture was analyzed using a gas chromatography (Perkin Elmer, Clarus 400) equipped with a flame ionization detector (FID) and capillary column. The crude product was purified by column chromatography (silica gel, 100-200 mesh; petroleum ether/ethyl acetate, 90:10) to afford pure products. All the prepared compounds were confirmed by comparing with their authentic samples and were characterized by GC-MS (Shimadzu QP 2010), 1H NMR (Varian 500 MHz).

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

Reference：
Article; Wagh, Yogesh S.; Sawant, Dinesh N.; Bhanage, Bhalchandra M.; Tetrahedron Letters; vol. 53; 27; (2012); p. 3482 – 3485;,
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,4318-42-7

To a stirred solution of aryl bromide (0.76 mmol) and amine (0.86 mmol) in dioxane (4 mL), was added XantPhos (0.048 mmol), cesium carbonate (1 .66 mmol) and Pd2(dba)3 (0.024 mmol). The mixture was stirred for 16 h at 90 °C, diluted with water and extracted into DCM (20 mL). The organic layers were passed through a phase separator and concentrated and the crude mixture was purified by flash silica column chromatography. Following method I from compound 15c (250 mg, 0.76 mmol) and /so-propylpiperazine (125 muIota, 0.86 mmol). Purification using flash silica column chromatography (gradient elution /’-hex/EtOAc 0percent to 100percent) gave the title compound as a yellow oil (187 mg, 65percent). LCMS (ES+) 379 (M+H)+

4318-42-7 1-Isopropylpiperazine 78013, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; CHDI FOUNDATION, INC.; LUCKHURST, Christopher A.; HAUGHAN, Alan F.; BRECCIA, Perla; STOTT, Andrew J.; BURLI, Roland W.; HUGHES, Samantha J.; MUNOZ-SANJUAN, Ignacio; DOMINGUEZ, Celia; MANGETTE, John E.; WO2012/103008; (2012); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

55112-42-0, 4-Methyl-1-piperazinecarbonyl Chloride Hydrochloride is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

N-(2-CHLORO-4-FLUOROPHENYL)-LS-PYRAZOLE-3-CARBOXAMIDE (50 mg, 209 UMOL, 1 equiv. ; see step (a) above) was mixed with the hydrochloride salt of 4-methyl-piperazine-1-carbonyl chloride (83 mg, 410 pmol, 2 equiv. ) and DMAP (50 mg, 410 mumol, 2 equiv. ) in toluene (5 mL) at 90C. The reaction mixture was left stirring for 16 h and then cooled. The precipitate from the reaction mixture was collected and recrystallised from EtOH/EtOAc to yield the hydrochloride salt of the title compound (a white powder). 0.5 M NaOH (AQ.) and ethyl acetate were added to the salt. The organic phase was dried and concentrated to afford the free base of the title compound as an off-white solid., 55112-42-0

The synthetic route of 55112-42-0 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; BIOLIPOX AB; MCNEENEY, Stephen, Phillip; WO2004/80999; (2004); 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.278788-66-2,(R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

278788-66-2, To a solution of tert-butyl (3R)-3-(hydroxymethyl)piperazine-1-carboxylate (80.0 g, 370 mmol, 1.0 eq) in Ethyl acetate (1400 mL) was added NaHCO 3 (93.2 g, 1.11 mol, 43.2 mL, 3.0 eq), H 2O (700 mL) and benzyl carbonochloridate (82.0 g, 481 mmol, 68.4 mL, 1.30 eq). The mixture was stirred at 25° C. for 12 hour. After completion, the organic phase was separated, washed with water (500 mL 2) dried over Na 2SO 4 and filtered. The solvent was removed under vacuum to give a residue. The residue was purified by column chromatography (SiO 2, Petroleum ether/Ethyl acetate=40/1 to 1/1). The product 1-benzyl 4-tert-butyl (2R)-2-(hydroxymethyl)piperazine-1,4-dicarboxylate (85.0 g, 235 mmol, 64% yield, 96% purity) was obtained as a yellow oil. LCMS [ESI, M-99]: 251.

As the paragraph descriping shows that 278788-66-2 is playing an increasingly important role.

Reference：
Patent; Mirati Therapeutics, Inc.; Array BioPharma Inc.; Blake, James F.; Burgess, Laurence E.; Chicarelli, Mark Joseph; Christensen, James Gail; Cook, Adam; Fell, Jay Bradford; Fischer, John P.; Marx, Matthew Arnold; Mejia, Macedonio J.; Savechenkov, Pavel; Vigers, Guy P.A.; Smith, Christopher Ronald; Rodriguez, Martha E.; US2019/144444; (2019); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

154590-35-9, tert-Butyl 4-(4-amino-2-fluorophenyl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Cool in ice a solution of the product of Preparation 17, Step 3 (1.53 g, 5.2 mmol) and DIPEA (1.10 ml, 6.2 mmol) in THF (40 ml). Add dropwise 4-bromobutyryl chloride (1.01 g, 5.4 mmol). Stir 2 h and partition with ether and satd. NaHCO3. Dry (MgSO4) and concentrate to obtain the carbamate as a yellow solid.

154590-35-9, The synthetic route of 154590-35-9 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Schering Corporation; US2005/239795; (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.278788-60-6,(R)-1-Boc-Piperazine-2-carboxylic acid,as a common compound, the synthetic route is as follows.

Trimethylsilyl diazomethane (2M in hexane, 14 ml) was added dropwise to a solution of (2R)-L-(TERT-BUTOXYVARBONYL) piperazine-2-carboxylic acid (5 g) in methanol (100 ml) and DCM (115 ml), and the solution stirred at room temperature for 16 hours. The solvent was concentrated in vacuo and the residue purified by chromatography, eluting with ethyl acetate then 5% methanol / 7N ammonia in ethyl acetate, to give 1-tert-butyl 2-methyl (2R)- PIPERAZINE-1, 2-dicarboxylate as an oil (2.55 g, 48%); NMR spectrum (DMSO-d6) 1.40 (s, 9H), 2.10 (bs, 1H), 2.52 (m, 1H), 2.72 (dd, 1H), 2.82 (d, 1H), 2.97 (m, 1H), 3.29 (d, 1H), 3.61 (d, 1H), 3.67 (s, 3H), 4.43 (m, 1H) ; Mass spectrum MH+ 245., 278788-60-6

278788-60-6 (R)-1-Boc-Piperazine-2-carboxylic acid 24820285, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2005/26152; (2005); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics