Month: May 2021

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

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.13754-38-6,1-Benzoylpiperazine,as a common compound, the synthetic route is as follows.

General procedure: A solution of 2-chloroalkyl/aryl substitutedwith or without N-substitution as well as with or without 5 and/or 6-substituted benzimidazole derivative (1.75g,0.01051mol) and 1-[(4-phenyl)carbonyl]piperazine (3g,0.0105mol) in N, N dimethylformamide was taken in a RBF.K2CO3(2gm,) was added to the reaction mixture. The reaction mixture was stirred for 8h at 80C on a magnetic stirrer (heat + stirring). The progress of the reaction was monitored by thin layer chromatography (TLC).Upon completion of the reaction, water was added to the reaction mixture and the product extracted by shaking the reaction mixture with dichloromethane in a separating funnel.The dichloromethane layer was washed successively with water and brine, dried over anhydrous sodium sulfate. Evaporation of the solvent gave theproduct. 11a-l Recrystallized with various solvent like chloroform, ethanol, methanol., 13754-38-6

As the paragraph descriping shows that 13754-38-6 is playing an increasingly important role.

Reference：
Article; Kankate, Rani S.; Gide, Parag S.; Belsare, Deepak P.; Oriental Journal of Chemistry; vol. 30; 4; (2014); p. 1855 – 1863;,
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.163765-44-4,(R)-1-Boc-3-Methylpiperazine,as a common compound, the synthetic route is as follows.

The (R) – 1-BOC-3-methyl-piperazine (300 mg, 1 . 5mmol) dissolved in acetonitrile (10 ml) in, adding DIEA (390 mg, 3mmol) and cyclopropyl methyl bromide (235 mg, 1 . 73mmol), 40 C reaction 2d, cessation of the reaction, the reaction liquid concentrated, column chromatography (DCM: the MeOH=40 […] 1) obtaining white semi-solid 320 mg, yield 84.2%., 163765-44-4

The synthetic route of 163765-44-4 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Institute Of Materia Medica Chinese Academy Of Medical Sciences; Xu, Bailing; Chen, Xiaoguang; Yao, Haiping; Ji, Ming; Jin, Jing; Zhou, Jie; Wang, Ke; Zhao, Dalong; (55 pag.)CN105461697; (2016); A;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

109-07-9, 2-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Example 8 In a 100 ml four-neck flask, 5.04 g (= 0.0503 mole) of racemic 2-methylpiperazine was placed, and 5.37 g of water and 45.13 g of 1-butanol were added for dissolution (water content 10.6 wt%). Furthermore, 3.99 g (= 0.0504 mole) of pyridine was added, being followed by stirring and subsequent cooling down to 0C, and 8.67 g of benzyl chlorocarbonate (= 0.0494 mole, purity by HPLC determination analysis 97.1 wt%, 0.98 molar time) was added dropwise with the liquid temperature kept in a range from 5 to 10C. Then, stirring was carried out at 0C for 2 hours. The reaction solution was analyzed, and as a result, the reaction yield of 1-benzyloxycarbonyl-3-methylpiperazine was 82.5%.

109-07-9, The synthetic route of 109-07-9 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Toray Fine Chemicals Co., Ltd.; EP1548010; (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.149057-19-2,4-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid,as a common compound, the synthetic route is as follows.

Step A: 4-Benzyl 1-(tert-butyl) 2-carbamoylpiperazine-1,4-dicarboxylate. NH4HCO3 (9 g, 114 mmol) was added to a solution of 4-((benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid (33 g, 91 mmol), Boc2O (25.7 g, 118 mmol), pyridine (4.3 g, 54 mmol), and 1,4-dioxane (462 mL). After 14 hours, the mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (300 mL) and the solution was washed with brine. The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to afford the title compound (36 g). This material was used in the next step without further purification. MS (ESI): mass calcd. for C18H25N3O5, 363.2; m/z found, 386.0 [M+Na]+.

149057-19-2, The synthetic route of 149057-19-2 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Janssen Pharmaceutica NV; Barbay, J. Kent; Chai, Wenying; Hirst, Gavin C.; Kreutter, Kevin D.; Kummer, David A.; McClure, Kelly J.; Nishimura, Rachel T.; Shih, Amy Y.; Venable, Jennifer D.; Venkatesan, Hariharan; Wei, Jianmei; (501 pag.)US2020/55874; (2020); 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.109-07-9,2-Methylpiperazine,as a common compound, the synthetic route is as follows.

Example 24A 3-methyl-1-pyridin-2-ylpiperazine hydrobromide 2-Methylpiperazine (1.0 g, 0.01 mol, racemic mixture) and 2-bromopyridine (10 mL, 0.1 mol) were combined and heated at 120 C. for 16 hours. The reaction mixture was cooled to 23 C. and partitioned between ethyl acetate and water. The layers were separated, and the water layer was concentrated under reduced pressure. The residue was triturated with ethyl acetate, dichloromethane, and methanol to afford 460 mg (26% yield) of the title compound as an off-white solid. 1H NMR (300 MHz, DMSO-d6) delta 1.27 (d, J=6.6 Hz, 3H), 2.90 (dd, J=10.5, 14.1 Hz, 1H), 3.10 (m, 2H), 3.40 (m, 2H), 4.32 (m, 2H), 6.77 (dd, J=4.8, 6.9 Hz, 1H), 6.98 (d, J=8.1 Hz, 1H), 7.64 (m, 1H), 8.15 (m, 1H), 8.63 (bs, 1H), 8.92 (bs, 1H); MS (APCI) m/e 178 (M+H)+.

109-07-9, The synthetic route of 109-07-9 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Cowart, Marlon D.; Bhatia, Pramila A.; Daanen, Jerome F.; Stewart, Andrew O.; Patel, Meena V.; Kolasa, Teodozyj; Brioni, Jorge D.; Rohde, Jeffrey; US2002/169166; (2002); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

278788-66-2, (R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Tert-butyl (R)-3-(hydroxymethyl)piperazine-1-carboxylate (384 mg, 1.78 mmol) was added to a mixture of 53 7-bromo-4,6-dichloro-3-nitroquinoline (260 mg, 0.81 mmol) and 56 DIPEA (0.316 ml, 1.78 mmol) in NMP (4 ml). The mixture was heated at 75 C. for 2 hours, then allowed to cool to room temperature. The mixture was partitioned between ethyl acetate (100 ml) and water (100 ml). The aqueous layer was extracted with ethyl acetate (100 ml) and the extracts combined with the organic layer. The combined organics were washed sequentially with water (2×100 ml) and saturated brine (50 ml), then dried and evaporated to dryness to give a brown gum. The crude product was purified by flash silica chromatography, elution gradient 20 to 40% 57 EtOAc in 58 heptane. Pure fractions were evaporated to dryness to afford 59 tert-butyl (R)-4-(7-bromo-6-chloro-3-nitroquinolin-4-yl)-3-(hydroxymethyl)piperazine-1-carboxylate (218 mg, 54%) as a yellow solid. 1H NMR (500 MHz, DMSO, 27 C.) 1.43 (9H, s), 3.34-3.53 (5H, m), 3.64 (3H, d), 4.34-4.42 (1H, m), 4.58 (1H, t), 8.38 (1H, d), 8.49 (1H, s), 9.05 (1H, s). m/z: ES+ [M+H]+ 501.

278788-66-2, 278788-66-2 (R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate 24820286, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; ASTRAZENECA AB; Kettle, Jason Grant; Bagal, Sharanjeet; Robb, Graeme Richard; Smith, James Michael; Goldberg, Frederick Woolf; Cassar, Doyle Joseph; Feron, James Lyman; US2019/177338; (2019); 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.120737-78-2,tert-Butyl 2-methylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

A mixture of ethyl 4,6-dimethyl-2-(4-methylpyridin-3-yl)pyrimidine-5-carboxylate (23)(23 mg, 85 mmol) and lithium hydroxide (50 mg, 2.09 mmol) in ethanol (3 mL) was heated at reflux for 3 h. The solvent was removed in vacuo before the residue was purified via reverse phase(C18) HPLC with a gradient elution of H2O/MeOH (100/0% to 10/90%) to afford compound 27 as an orange-brown solid (18 mg, 87%). 1HNMR (D2O, MeOD) d: 8.77 (s, 1H), 8.43 (d, J4.8 Hz, 1H), 7.39 (d,J4.8 Hz, 1H), 2.59 (s, 6H), 2.53 (s, 3H). 13C NMR (D2O, MeOD) d:170.5, 163.2, 162.6, 150.8, 149.8, 149.0, 136.3, 133.8, 127.5, 22.3, 20.4.LRMS (ESI): m/z 244.1 [MH] (100%); (ESI): m/z 242.0 [MH](100%).A solution of 4,6-dimethyl-2-(4-methylpyridin-3-yl)pyrimidine-5-carboxylic acid (27) (40 mg, 0.16 mmol), ()-tert-butyl 2-methylpiperazine-1-carboxylate45 (36 mg, 0.18 mmol), HOBt(24 mg, 0.18 mmol), EDCI (36 mg, 0.18 mmol) and DIPEA (0.08 mL,0.33 mmol) in DCM (10 mL) was stirred at room temperature for 18 h. The reaction mixture was diluted in H2O, extracted with DCM (310 mL), and the combined organic layers concentrated to 3 mL.To the solution was then added 10 drops of TFA before stirring for 3 h. The reaction mixture was then extracted with H2O (33 mL)and the combined aqueous layers freeze dried. The residue was purified via reverse phase (C18) HPLC with a gradient elution ofH2O/MeOH (100/0% to 10/90%), to afford the desired product asa pale yellow solid (4 mg, 7%) as a mixture of conformers. 1H NMR (MeOD) d: 8.44 (br s, 1H), 7.64e7.58 (m, 1H), 7.45 (m, 1H), 7.15e7.07(m, 1H), 4.59 (m, 2H), 3.95 (br s, 2H), 3.63e3.06 (complex, 6H), 2.39(br s, 3H), 1.32 (m, 3H). 13C NMR (MeOD) d: 157.0, 148.9, 147.8,139.2, 129.7, 129.4, 127.4, 127.0, 125.2, 123.4, 123.1, 113.6, 113.3, 52.0,51.9, 47.1, 30.7, 19.9, 17.1, 16.9. HRMS (APCI): m/z calcd forC18H24N5O [MH]: 326.1981, found: 326.1978; (APCI): m/z calcdfor C19H22N4O [MH]: 324.1824, found: 324.1829., 120737-78-2

The synthetic route of 120737-78-2 has been constantly updated, and we look forward to future research findings.

Reference：
Article; Lim, Zelong; Duggan, Peter J.; Wan, Soo San; Lessene, Guillaume; Meyer, Adam G.; Tuck, Kellie L.; Tetrahedron; vol. 72; 9; (2016); p. 1151 – 1160;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics