Heterocyclic Building Blocks-piperazine

55121-99-8,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.55121-99-8,(4-Aminophenyl)(4-methylpiperazin-1-yl)methanone,as a common compound, the synthetic route is as follows.

3,5-Dibromopyridine (249 mg, 1.05 mmol), [l-(tert-butoxycarbonyl)-H-indol-2- yl]boronic acid (302 mg, 1.16 mmol), Pd(PPh3J4 (61 mg, 0.05 mmol) and Na- HCO3 (309 mg, 3.68 mmol) in DME/water (3.5: 1, 4.5 mL) was irradiated with microwaves at 120 0C for 5 minutes, followed by 180 0C for 12 minutes. The reaction mixture was extracted with DCM (2×10 mL) and water (10 mL). The organic layers were combined, dried (Na2SO4), filtered and concentrated. The residue was purified by preparative HPLC (YMC ODS-AQ, 0.1% TFA-MeCN) to give 2-(5-bromopyridin-3-yl)-lH-indole. 2-(5-bromopyridin-3-yl)-lH-indole (10 mg, 0.04 mmol), {4-[(4-methylpiperazin-l-yl)carbonyl]phenyl}amine (12 mg, 0.06 mmol), Pd(OAc)2 (2 mg, 0.01 mmol), NaOtBu (12 mg, 0.13 mmol) and Xantphos (9 mg, 0.018 mmol) in toluene /tBuOH (5: 1, ImL) was irradiated with micro waves at 160 0C for 20 minutes. Additional Pd(OAphi (5 mg, 0.02 mmol) was added and the resulting mixture was irradiated with micro waves for a further 20 min at 160 0C. The crude mixture was extracted with EtOAc and 1 M aq NaOH and the product precipitated and was filtered off. The crude product was purified by preparative HPLC (ACE C8, 0.1% TFA, MeCN) followed by (XTerra C 18, 5OmM NH4HCO3 pH 10, MeCN). This gave the title compound as a white solid (0.7 mg). MS (ESI+) for C25H25N5O m/z 412 (M+H)+. HPLC 100%(System A), 96%(System B).

The synthetic route of 55121-99-8 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; BIOVITRUM AB (PUBL); WO2007/147874; (2007); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

694499-26-8, 4-((4-Methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,694499-26-8

General procedure: To amixture of substituted benzoic acid obtained in the last step (0.12 mmol) in 5mL DMF, 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate (HATU, 0.18 mmol), ethyldiisopropylamine (DIPEA, 0.24 mmol)and 4-((4-methylpiperazin-1-yl)methyl)-3- (trifluoromethyl)aniline (0.1 mmol)was added. The resulting mixture was stirred at room temperature overnight. Thenthe reaction was extracted with ethyl acetate, washed with brine, dried overanhydrous Na2SO4, filtered and concentrated to give thecrude product, which was further purified by column chromatography to affordthe final compounds.

The synthetic route of 694499-26-8 has been constantly updated, and we look forward to future research findings.

Reference：
Article; Han, Mei; Li, Shan; Ai, Jing; Sheng, Rong; Hu, Yongzhou; Hu, Youhong; Geng, Meiyu; Bioorganic and Medicinal Chemistry Letters; vol. 26; 23; (2016); p. 5679 – 5684;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5464-12-0, 1-(2-Hydroxyethyl)-4-methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

5464-12-0, G) 4-(2-Fluoro-4-nitrophenoxy)-5-methyl-6-(2-(4-methylpiperazin-1-yl)-ethoxy)pyrrolo[2,1-f][1,2,4]triazine To a homogeneous mixture of 4-(2-fluoro-4-nitrophenoxy)-5-methylpyrrolo[2,1-f][1,2,4]-triazin-6-ol (100 mg, 0.33 mmol) and triphenylphosphine (129 mg, 0.49 mmol) in 4 mL of 1:1 anhydrous dichlormethane/anhydrous tetrahydrofuran, cooled to 0° C. under a nitrogen atmosphere, was added dropwise a mixture of 2-(4-methylpiperazin-1-yl)ethanol (71 mg, 0.49 mmol) and diisopropylazodicarboxylate (0.10 muL, 0.49 mmol) in 2 mL of 1:1 anhydrous dichlormethane/anhydrous tetrahydrofuran. The mixture was stirred and allowed to warm to room temperature. The reaction was stirred for twelve hours before being concentrated in vacuo. The residue was purified by preparative HPLC (YMC S10 ODS, 30*500 mm, 30 minute gradient from 50percent to 90percent aqueous methanol with 0.1percent TFA). The appropriate fractions were combined, neutralized with saturated aqueous sodium bicarbonate, and then concentrated in vacuo to remove methanol. The mixture was extracted with chloroform (3*10 mL). The combined organic layers were washed once each with water and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo to yield the title compound (34 mg, 24percent) as a yellow solid. 1H NMR (CDCl3) delta 8.20-8.10 (m, 2H), 7.82 (s, 1H), 7.58-7.52 (m, 1H), 7.49 (s, 1H), 4.16 (t, 2H, J=5.7 Hz), 2.87 (t, 2H, J=5.7 Hz), 2.80-2.40 (m, 8H), 2.45 (s, 3H), 2.31 (s, 3H); MS(ESI+) m/z 431.3 (M+H)+.

As the paragraph descriping shows that 5464-12-0 is playing an increasingly important role.

Reference：
Patent; Bristol-Myers Squibb Company; US2007/123534; (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.31166-44-6,1-Cbz-Piperazine,as a common compound, the synthetic route is as follows.

Benzyl 4-(2-((tert-butoxycarbonyl)amino)acetyl)piperazine-l-carboxylate. To a mixture of N-Cbz-piperazine (2.2 mL, 11.4 mmol) and Boc-Gly-OH (1.8 g, 10.4 mmol) in DMF (20 mL) was added BOP (6.0 g, 13.6 mmol) and diisopropylethylamine (5.4 mL, 31.2 mmol). After stirring for 16h at rt, the resulting mixture was treated with saturated brine and then extracted with EtOAc. The combined organic layers were washed with 5percent aqueous NaHCCte and saturated brine, dried over sodium sulfate, filtered, and concentrated. The residue as purified by flash column chromatography eluting with Hexane:EtOAc (1 :2) to obtain benzyl 4-(2-((tert- butoxycarbonyl)amino)acetyl)piperazine-l-carboxylate (3.5 g, 89 percent yield) as a viscous oil. ESI-MS [M+Na]= 400.2; 1H NMR (600 MHz, CDCb) delta 7.39-7.2691 (m, 5H), 5.47 (br s, 1H), 5.15 (s, 2H), 3.96 (d, 2H, J=4.2), 3.62 (br s, 2H), 3.55-3.50 (m, 4H), 3.38 (br s, 2H), 1.45 (s, 9H).

31166-44-6, 31166-44-6 1-Cbz-Piperazine 643495, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; PRESIDENT AND FELLOWS OF HARVARD COLLEGE; THE BRIGHAM AND WOMEN’ S HOSPITAL, INC.; CUNNINGHAM, James; LEE, Kyungae; REN, Tao; CHANDRAN, Kartik; WO2013/22550; (2013); 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.182618-86-6,1-Boc-4-(4-Nitrophenyl)piperazine,as a common compound, the synthetic route is as follows.

Add 1 g of crude I-i (32.6 mmol) to a 500 mL single-necked flask. 1.0 g of FeO(OH)/C catalyst and 100 mL of 95% ethanol, heated to reflux. Slowly add a mixture of 10 mL of hydrazine hydrate and 20 mL of 95% ethanol. The disappearance of the starting material by TLC (methanol: chloroform = 1:15). The filter cake was washed twice with hot ethanol (30 mL × 2). The solvent was evaporated under reduced pressure to give a white solid. It was dried under vacuum to give (I-j) 7.86 g, yield: 87.1%. The product was directly fed to the next reaction without further purification.

182618-86-6, As the paragraph descriping shows that 182618-86-6 is playing an increasingly important role.

Reference：
Patent; China Pharmaceutical University; Wang Yue; Lu Shuai; Zhi Yanle; Yao Chao; Lu Tao; Li Baoquan; Chen Puzhou; Bao Jiyin; (26 pag.)CN109970717; (2019); A;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

21655-48-1, cis-2,6-Dimethylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

In a sealed tube, 2-(2,8-dimethylimidazo[l,2-b]pyridazin-6-yl)-7-fluoro-pyrido[l,2- a]pyrimidin-4-one (Intermediate 2; 50 mg, 0.162 mmol), and cis-2,6-dimethylpiperazine (74 mg, 0.647 mmol, 4.0 eq.) were stirred in DMSO (1.5 mL) at 110C overnight. The solvent was removed under high vacuum. The residue was taken up in CH2CI2and washed with an aqueous saturated solution of NaHC03. The organic layer was separated and dried over Na2S04and concentrated in vacuo. The crude was purified by column chromatography (S1O2,CH2Cl2/MeOH=95/5 to 90/10) to afford the title product (32 mg, 49%) as a light yellow solid. MS m/z 404.4 [M+H+]., 21655-48-1

As the paragraph descriping shows that 21655-48-1 is playing an increasingly important role.

Reference：
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; MCCARTHY, Kathleen Dorothy; METZGER, Friedrich; RATNI, Hasane; (76 pag.)WO2017/81111; (2017); 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.154590-35-9,tert-Butyl 4-(4-amino-2-fluorophenyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

Cool in ice a solution of the product of Preparation 17, Step 3 (1.50 g, 5.1 mmol) in THF (40 ml). Add DIPEA (1.08 ml, 6.2 mmol), then 2-chloroethyl chloroformate (0.76 g, 5.3 mmol). Stir 3 h and partition with ether and satd. NaHCO3. Dry (MgSO4) and concentrate to obtain the carbamate as a brown solid.

154590-35-9, As the paragraph descriping shows that 154590-35-9 is playing an increasingly important role.

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.208167-83-3,tert-Butyl 4-(2-chloroethyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.,208167-83-3

Step 8: Preparation of tert-butyl 4-[2-[4-(6-benzyloxy-2-phenyl-3,4-dihydro-1H-isoquinolin-1-yl)phenoxy]ethyl]piperazine-1-carboxylate To a solution of 4-(6-benzyloxy-2-phenyl-3,4-dihydro-1H-isoquinolin-1-yl)phenol (2.30 g, 5.64 mmol, 1.00 eq), tert-butyl 4-(2-chloroethyl)piperazine-1-carboxylate (1.68 g, 6.77 mmol, 1.20 eq) in N,N-dimethylformamide (20 mL) was added cesium carbonate (2.76 g, 8.46 mmol, 1.50 eq) and potassium iodide (94 mg, 0.56 mmol, 0.10 eq) under nitrogen atmosphere. The reaction mixture was stirred at 90 C. for 16 hours. LC/MS showed most of the starting material was consumed. Water (150 mL) was added to the mixture, the resulting mixture was extracted with ethyl acetate (50 mL*3). The combined organic phase was washed with brine (100 mL*2), dried over sodium sulfate, filtered and concentrated in vacuum. The residue was purified by silica gel chromatography (petroleum ether/ethyl acetate=20/1 to 1/1) to give tert-butyl 4-[2-[4-(6-benzyloxy-2-phenyl-3,4-dihydro-1H-isoquinolin-1-yl) phenoxy]ethyl]piperazine-1-carboxylate (2.5 g, 3.97 mmol, 70% yield, 98% purity) as a yellow solid. LC/MS (ESI) m/z: 620.3 [M+1]+; 1H-NMR (400 MHz, DMSO-d6) delta 7.44-7.37 (m, 4H), 7.32-7.28 (m, 2H), 7.17-7.11 (m, 4H), 6.87-6.80 (m, 6H), 6.64 (t, J=7.2 Hz, 1H), 5.84 (s, 1H), 5.07 (s, 2H), 4.06-3.98 (m, 2H), 3.67-3.62 (m, 1H), 3.44-3.40 (m, 1H), 3.29-3.27 (m, 4H), 2.96-2.79 (m, 2H), 2.65 (t, J=5.6 Hz, 2H), 2.39 (t, J=4.8 Hz, 4H), 1.38 (s, 9H).

208167-83-3 tert-Butyl 4-(2-chloroethyl)piperazine-1-carboxylate 22106269, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; Arvinas, Inc.; Crew, Andrew P.; Qian, Yimin; Dong, Hanqing; Wang, Jing; Hornberger, Keith R.; Crews, Craig M.; (864 pag.)US2018/155322; (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.103-76-4,N-(2-Hydroxyethyl)piperazine,as a common compound, the synthetic route is as follows.

2-(4-Methylpiperazin-1-yl)ethyl 4-nitrophenyl carbonate To a stirred solution of 1-(2-hydroxyethyl)piperazine (26.0 g, 0.2 mol) in DMF (200 mL) was added formic acid (752 mL, 0.2 mol) and formaldehyde (16.2 g, 0.2 mol, 37% solution in water) The reaction mixture was cautiously heated at 100 C. for 2 hours then stirred overnight at room temperature. The solvent was removed in vacuo. This procedure was repeated 3 further times to give ~100 g of product. The crude products were combined and distilled under vacuum to give, at 74 C., 2-(4-methylpiperazin-1-yl)ethanol (51 g, 44%) as a colourless liquid. Analytical LCMS: (System C, RT=0.70 min), ES+: 145.1 [MH]+., 103-76-4

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

Reference：
Patent; Biovitrum AB; US2009/281087; (2009); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

21091-98-5, (4-Methylpiperazin-1-yl)(4-nitrophenyl)methanone is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

(4-Methylpiperazin-1-yl)(4-nitrophenyl)methanone (31.5 g, 126 mmol) was dissolved in methanol (150 ml) and transferred into a 500-ml PARR flask. The PARR flask was flushed with nitrogen, then 500 mg Pd/C (10% Pd) were added. The flask was flushed with nitrogen, then hydrogen, then shaken under a pressure of 50 psi of hydrogen for 17 hours. The mixture was filtered through CELITE, the solid washed with MeOH and concentrated to give 27.2 g beige solid ((4-aminophenyl)(4- methylpiperazin-1-yl)methanone. MS (ESI) m/z 220 (M+H). 1H NMR (CDCl3) delta ppm 7.25 (d, 2 H, J= 7.6), 6.64 (d, 2 H, J= 7.6), 3.86 (bs, 2 H), 3.63 (bs, 4 H), 2.40 (bs, 4H), 2.30 (s, 3H)., 21091-98-5

21091-98-5 (4-Methylpiperazin-1-yl)(4-nitrophenyl)methanone 716396, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; BRISTOL-MYERS SQUIBB COMPANY; PURANDARE, Ashok, Vinayak; BATT, Douglas, G.; LIU, Qingjie; JOHNSON, Walter, L.; MASTALERZ, Harold; ZHANG, Guifen; ZIMMERMANN, Kurt; WO2010/80474; (2010); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics