Heterocyclic Building Blocks-piperazine

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.16154-72-6,3-Chloro-4-(4-methylpiperazin-1-yl)benzenamine,as a common compound, the synthetic route is as follows.

To a solution of 3.0 g (13.3 mmol) OF 4- (3-CHLORO-4-METHYLPIPERAZIN-1-YL) aniline and 2.22 mL (16.0 mmol) of triethylamine in 36 mL of dichloromethane, 6.0 g (15.3 mmol) of 1, 3-bis (TERT-BUTOXYCARBONYL)-2-TRIFLUOROMETHANESULFONYLGUANIDINE were added. The reaction mixture was stirred at room temperature for 72 hours. The solution was diluted with FURTHER dichloromethane, washed with water and the solvent dried over NA2S04 and evaporated in vacuo. The residue was purified by chromatography on a silica gel column (eluant dichloromethane/methanol 92/8) giving 5.4 g (86.2% yield) of a protected intermediate, that was treated with 60 mL OF 4 N HC1 in dioxane. The mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, the residue redissolved in water, the resulting solution neutralized and the product extracted with ethyl acetate. The solvent was removed under reduced pressure to give 2.4 g (78.7% yield) of the title compound. H NMR (400 MHz, DMSO-d6) 8 ppm 2.23 (s, 3 H) 2.48 (m, 4 H) 2.90 (m, 4 H) 5.38 (bs, 4 H) 6.72 (dd, J2. 44,8. 42 Hz, 1 H) 6.82 (d, J2. 44, 1 H) 7.01 (d, J8. 42 Hz, 1 H).

16154-72-6, As the paragraph descriping shows that 16154-72-6 is playing an increasingly important role.

Reference：
Patent; PHARMACIA ITALIA S.P.A.; WO2004/104007; (2004); A1;,
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

A vial was charged with (S)-tert-butyl 3 -(hydroxymethyl)piperazine-l -carboxylate (367.3 mg, 1.647 mmol) and 2-(tert-butoxymethyl)oxirane (243.3 mg, 1.850 mmol) in ethanol (3 mL). The mixture was heated at 120 C for 30 min using microwave. The mixture was cooled to room temperature, concentrated to remove all of solvents. The residue was purified with flash column chromatography on silica gel using 1-10% methanol in dichloromethane to afford the final product as colorless oil (497.5 mg) in 87% yield. NMR (500 MHz, Chloroforn /) delta 3.86 – 3.80 (m, 2H), 3.71 – 3.68 (m, lH), 3.53 – 3.41 (m, 2H), 3.40 – 3.35 (m, 2H), 3.24 (dd, J = 9.1, 6.6 Hz, 1H), 3.10 (br, 1H), 2.91 (m, 1H), 2.83 – 2.75 (m, 1H), 2.48 (dd, J = 13.1, 7.6 Hz, 2H), 2.39 – 2.30 (m, 1H), 1.44 (s, 9H), 1.18, 1.17 (2s, 9 H). MS for C17H34N2O5: 347.2 (MH+)., 314741-40-7

The synthetic route of 314741-40-7 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; NEKTAR THERAPEUTICS (INDIA) PVT. LTD.; NEKTAR THERAPEUTICS; SHARMA, PANKAJ; KHATRI, VIJAY KUMAR; GU, XUYUAN; SONG, YUAN; SHEN, MICHAEL LIXIN; SAUTHIER, JENNIFER RIGGS; ANAND, NEEL K.; KOZLOWSKI, ANTONI; ODINECS, ALEKSANDRS; RILEY, TIMOTHY A.; REN, ZHONGXU; MU. YONGQI; SHEN, XIAOMING; YUAN. XUEJUN; AURRECOECHEA, NATALIA; O’MAHONY, DONOGH JOHN ROGER; WO2015/92819; (2015); 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.39539-66-7,4-Methylpiperazine-1-carbonyl chloride,as a common compound, the synthetic route is as follows.

EXAMPLE 28 Triethylamine (3.4 cc. equivalent to 2.44 g.), followed by pyridine (15 cc.) are added to a suspension of 2-(7-chloro-1,8-naphthyridin-2-yl)-5-fluoro-3-hydroxy-1-isoindolinone (2 g.) and 4-chlorocarbonyl-1-methyl-piperazine hydrochloride (3.6 g.) in methylene chloride (30 cc.). The suspension obtained is heated to the reflux temperature (55 C) for 1 hour and further 4-chlorocarbonyl-1-methylpiperazine (3.6 g.) and triethylamine (3.4 cc.) are then added. The mixture is further heated to the reflux temperature for 45 minutes. After cooling, methylene chloride (30 cc.) and water (60 cc.) are added. After phase separation, the aqueous layer is extracted with methylene chloride (60 cc.). The organic extracts are dried over anhydrous sodium sulphate. After filtration and concentration, the residue is triturated in water (30 cc.). The precipitate is filtered off and dried in air. The crude product is recrystallized from acetonitrile (64 cc.). The product is filtered off and then washed with isopropyl ether (60 cc.). This gives 2-(7-chloro-1,8-naphthyridin-2-yl)-5-fluoro-3-(4-methylpiperazinyl)-carbonyloxy-1-isoindolinone (0.8 g.) melting at 247-248 C. 2-(7-chloro-1,8-naphthyridin-2-yl)-5-fluoro-3-hydroxy-1-isoindolinone can be prepared in the following manner:

39539-66-7, The synthetic route of 39539-66-7 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Rhone-Poulenc S.A.; US4016274; (1977); A;,
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.170911-92-9,tert-Butyl 4-(4-aminophenyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

c (6 g, 21.63 mmol), triethylamine (3.28 g, 32.45 mmol) were added to 100 mL of CH 2 Cl 2 under ice-cooling, and then 3-chloro-benzoyl chloride (4.54 g, 25.96 mmol) was gradually added dropwise. After being transferred to room temperature, stirring for 2 hours;After the reaction was completed, it was quenched by adding 50 mL of water, and then 50 mL of CH2Cl2 solvent was added.After washing with water (50 mL × 3), the organic phase was dried over anhydrous magnesium sulfate,Evaporation to dry d (7.60 g); yield: 84.47%,, 170911-92-9

As the paragraph descriping shows that 170911-92-9 is playing an increasingly important role.

Reference：
Patent; Zhejiang University; Zhengzhou University; Sun Yi; Liu Hongmin; Xu Tiantian; Li Yanan; Yu Bin; Ma Qisheng; Hou Tingjun; Pan Peichen; Xiong Xiufang; (37 pag.)CN110156729; (2019); A;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

74879-18-8,74879-18-8, (S)-(+)-2-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

2.23 Example 23 (Prepared according to Scheme 4); (S)-4-(3-Chloropyridin-2-yl)-2-methyl-N-(4-(trimethylsilyl)phenyl)piperazine-l-carboxamide; A solution of 2,3-dichloropyridine (3mmol), (5)-(+)-2-methylpiperazine (3mmol) and TEA (9mmol) in DMSO (20 ml) was heated to 100 C for 18 hrs. The reaction mixture was diluted with MeOH (20 ml) and put onto an SCX cartridge. The cartridge was washed with MeOH before eluting the product off with 2M ammonia in MeOH. The appropriate fractions were collected and concentrated under reduced pressure. The resulting residue was purified by flash chromatography (60-80 % ethyl acetate in petroleum ether on KPNH cartridge) yielding (S)-l-(3-chloropyridine-2-yl)-3-methylpiperazine (2.1mmol).MS: ES+ 212.10. 1H NMR (400 MHz, DMSO-d6) delta 8.14 – 8.28 (m, IH), 7.67 – 7.87 (m, IH), 6.84 – 7.08 (m, IH), 3.49 – 3.62 (m, 2H), 2.87 – 2.96 (m, IH), 2.77 – 2.87 (m, 2H), 2.62 – 2.77 (m, IH), 2.51 (s, IH), 2.34 – 2.44 (m, IH), 0.92 – 1.10 (m, 3H)A solution of (,S>;-l-(3-chloropyridine-2-yl)-3-methylpiperazine (0.53mmol) and Intermediate 1 (0.53mmol) in ethanol (2 ml) was heated in the microwave to 100 0C for 30 min. The reaction mixture was concentrated under educed pressure and the resulting residue was purified by flash chromatography (20-40 % ethyl acetate in petroleum ether) yielding the title compound (0.32 mmol).MS ES- 401.20. 1H NMR (400 MHz, DMSO-d6) delta 8.32 (s, IH), 8.00 – 8.07 (m, IH), 7.57 – 7.66 (m, IH), 7.22 – 7.30 (m, 2H), 7.1 1 – 7.20 (m, 2H), 6.78 – 6.88 (m, IH), 4.26 (br. s., IH), 3.77 (br. s., IH), 3.41 – 3.52 (m, 2H), 2.98 – 3.08 (m, IH), 2.55 – 2.77 (m, 2H), 1.04 – 1.13 (m, 3H), 0.00 (s, 9H)

As the paragraph descriping shows that 74879-18-8 is playing an increasingly important role.

Reference：
Patent; TAKEDA PHARMACEUTICAL COMPANY LIMITED; AYSCOUGH, Andrew Paul; SHOWELL, Graham Andrew; TEALL, Martin Richard; TEMPLE, Hannah Elizabeth; AHMED, Saleh; WO2010/92342; (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.325145-35-5,(S)-tert-Butyl 2-ethylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

To a solution of 5-chloro-1- (chloromethyl) -2-methyl-3-nitrobenzene (D23 1.232 g) in DMF (20 mL) were added (S) -tert-butyl 2-ethylpiperazine-1-carboxylate (1 g) and K2CO3(1.935 g) at 60. After stirring overnight the mixture was poured into ice/water and then extracted with DCM (3×100 mL) . The combined organic layers were dried over Na2SO4 filtered and concentrated to give a yellow oil which was purified by column chromatography (eluting with EAPE5) to give the title compund (1.3 g) as a yellow solid. MS (ESI) C19H28ClN3O4requires 397 found 398 [M+H]+., 325145-35-5

The synthetic route of 325145-35-5 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; GLAXOSMITHKLINE (CHINA) R&D COMPANY LIMITED; LEI, Hui; MA, Xin; REN, Feng; LIN, Xichen; MARQUIS, Robert W., Jr.; WO2015/180614; (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.3022-15-9,Piperazine-2-carboxylic acid dihydrochloride,as a common compound, the synthetic route is as follows.,3022-15-9

piperazine-2-carboxylic acid dihydrochloride (10.0 g, 49.23 mmol) is dissolved in 1:1 dioxane/water (320 ml). 50% Aqueous sodium hydroxide is added to bring the pH to 11. BOC-ON (2-(tert-butoxycarbonyloxyimino)-2-phenylacetonitrile), (15.59 g, 63.32 mmol) is dissolved in dioxane (80 ml) and added dropwise while maintaining the pH at 11 with 50% aqueous sodium hydroxide. The reaction is stirred overnight at ambient temperature. The reaction mixture is then extracted with diethyl ether (5×250 ml) and acidified to pH 2 with concentrated hydrochloric acid. The di-Boc compound is then extracted out with ethyl acetate (4×200 ml) and the acidic aqueous solution containing the desired mono-Boc product is then taken on in the synthesis.

The synthetic route of 3022-15-9 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Aventis Pharmaceuticals Inc.; US7138526; (2006); B1;,
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.109-01-3,1-Methylpiperazine,as a common compound, the synthetic route is as follows.

4-nitrobenzylbromide (4.30 g, 20 mmol) was dissolved in 40 ml of acetonitrile solvent,Then K2CO3 (5.52 g, 40 mmol) was added,KI (0.33 g, 2 mmol),Then, 4-methylpiperazine (2.20 g, 22 mmol) was added thereto,After 5 h, the reaction was complete.The reaction solution was concentrated and dried,And further adding 100 ml of H2O thereto,Extracted with ethyl acetate (150 ml x 3)The organic layer was collected, concentrated,4.32 g of a solid was obtained in 92% yield., 109-01-3

109-01-3 1-Methylpiperazine 53167, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; Nantong University; Ling, Yong; Mou, Jiefei; Xu, Qibing; Feng, Jiao; Zhu, Peng; Liu, Ji; Wang, Tingting; Ge, Xiang; Liang, Shanshan; (26 pag.)CN106432235; (2017); A;,
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

To (E)-3-(2-((5-methyl-2 H-tetrazol-2-yI)methyl)-4-(trifluoromethyl) phenyl)acrylic acid(Intermediate AB) (100 mg, 0.320 mmol) in NMP (1.5 mL) was added HATU (146 mg, 0.384 mmol) and the mixture was stirred for 5 minutes. (S)-tert-Butyl 3-(hydroxymethyl) piperazine1-carboxylate (69.3 mg, 0.320 mmol) was added followed by DIPEA (0.168 mL, 0.961 mmol) and the reaction mixture was stirred at room temperature for 2 h. The resulting mixture was poured into water and extracted with EtOAc. The organics were washed with water,saturated sodium bicarbonate solution, water, brine and dried using a phase separating column. The solvent was removed under reduced pressure. Purification of the crude product by chromatography on silica using a gradient from 0 – 100% EtOAc in iso-hexane afforded the title compound;LC-MS: Rt = 1.30 mins; [M+H] 511.3, Method 2minHighpHvo3.1H NMR (400 MHz, DMSO-d6) O 8.12-7.98 (1H, mult), 7.90-7.72 (3H, mult), 7.22 (1H, d),6.11 (2H, 5), 4.90 (1H, br), 4.56-3.74 (4H, mult), 3.45 (2H, br), 3.06-2.74 (3H mult), 2.42 (3H,5), 1.42 (9H, 5).

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; NOVARTIS AG; BEATTIE, David; BAETTIG, Urs; LEGRAND, Darren Mark; LISTER, Andrew Stuart; MCKENNA, Jeffrey; PEARCE, David William; SANDHAM, David Andrew; STEWARD, Oliver Ross; THOMSON, Christopher; WO2015/8230; (2015); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

548762-66-9, (2S,5R)-tert-Butyl 2,5-dimethylpiperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Half of the solid from the previous step was treated with N,N-diisopropylethylamine (0.5 mL, 3 mmol), DMSO (0.5 mL, 7 mmol) and (2S,5R)-2,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester (273 mg, 1.27 mmol) and the reaction mixture was heated at 120 C overnight, concentrated by rotary evaporation, dissolved in a small amount of DCM and purified by silica gel chromatography (0-50% ethyl acetate:hexanes) to produce the title intermediate (288 mg, 29 % yield) as a yellow solid. (m/z): [M+H]+ calcd for C24H27F4N4O4 591.09, 593.09 found 593.2.

548762-66-9, As the paragraph descriping shows that 548762-66-9 is playing an increasingly important role.

Reference：
Patent; Theravance Biopharma R&D IP, LLC; MCKINNELL, Robert Murray; LONG, Daniel D.; VAN ORDEN, Lori Jean; JIANG, Lan; LOO, Mandy; SAITO, Daisuke Roland; ZIPFEL, Sheila; STANGELAND, Eric L.; LEPACK, Kassandra; OGAWA, Gavin; HUANG, Xiaojun; ZHANG, Weijiang; EP2635571; (2015); B1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics