Heterocyclic Building Blocks-piperazine

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.75336-86-6,(R)-2-Methylpiperazine,as a common compound, the synthetic route is as follows.,75336-86-6

EXAMPLE 29; Example 29A; Step 1; (R)-2-methyl-piperazine (3.5 g, 34.9 mmol), 2-bromo-5-fluoro benzotri fluoride (7.74 g, 31.7 mmol), BlNAP (0.59 g, 0.95 mmol), tBuONa (4.58 g, 47.65 mmol) and Pd2(dba)3 (0.29 g, 0.32 mmol) were mixed in the flask and purged with N2. Anhydrous toluene (50 mL) was added and purged with N2 again. The resulting mixture was heated in an oil bath at 1000C under N2 for 3 hours. The mixture was cooled to room temperature, diluted with dichloromethane (150 mL), washed with H2O (30 mL) first, then washed with saturated brine (30 mL). The combined organic layer was dried over Na2SO4, concentrated down under reduced pressure to give a brown color liquid as crude. The crude product was purified on silica gel column eluted with 5-10percent MeOH in DCM to give (3lambda)-l-[4-fluoro-2-(trifluoromethyl)phenyl]-3-methylpiperazine as a light yellow oil (6.85 g, 82percent).; Example 29AX. 3-(((2R)-4-r4-fluoro-2-ftrifluoromethyl)phenyll-2-methylpiperazin-l – yl ) sulfonvDphenol; Step A; (R)-2-methyl-piperazine (3.88 g, 38.70 mmol), 2-bromo, 5-fluoro benzotrifluoride (8.55 g, 35.18 mmol), tris(dibenzylidineacetone)dipalldium (0) (32.0 mg g, 0.35 mmol), rac-2,2′-bis(diphenylphosphino)-l,l’-binaphthyl (657.0 mg, 1.06 mmol) and sodium tert- butoxide (5.07 g, 52.77 mmol) were charged to a reaction flask. Toluene (40 mL) was introduced under nitrogen atmosphere and the reaction mixture was heated up at 11O0C for 5.0 hours. Reaction was complete as determined by TLC. The reaction mixture was diluted with dichloromethane, washed with water, saturated brine then dried over MgSO4 and concentrated. The crude product was purified via flash column chromatography to yield (R)-I -(4-fluoro-2- (trifluoromethyl)phenyl)-3-methylpiperazine as a light brown oil (3.1 g, 33.6percent yield).

75336-86-6 (R)-2-Methylpiperazine 7330434, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; WYETH; WO2007/92435; (2007); A2;,
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509073-62-5, tert-Butyl 4-(4-nitrobenzoyl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

[0260j A mixture of tert-butyl 4-(4-nitrobenzoyl)piperazine- 1 -carboxylate (20 g, 60 mmol) and 10% Pd/C (4 g) in MeOH (600 mL) was stirred under 1 atmosphere of H2 at room temperature for for 18 h. The solution was filtered through Celite and the filtrate was concentrated under reduced pressure to afford 18 g of tert-butyl 4-(4- aminobenzoyl)piperazine-1-carboxylate as a white solid (100%).

509073-62-5, 509073-62-5 tert-Butyl 4-(4-nitrobenzoyl)piperazine-1-carboxylate 2764459, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; CATABASIS PHARMACEUTICALS, INC.; MILNE, Jill C.; JIROUSEK, Michael R.; VU, Chi B.; WO2013/177536; (2013); A2;,
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75336-86-6, (R)-2-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Step 5 A: A mixture of (R)-2-methyl-piperazine (6.0 g, 59.9 mmol), 4-chloro-3- trifluoromethyl-benzonitrile (11.2 g, 54.5 mmol), tris(dibenzylidineacetone)dipalldium (0) (0.499 g, 0.545 mmol), rac-2,2′-bis(diphenylphosphino)-l,l ‘-binaphthyl (1.02 g, 1.635 mmol)and sodium tert-butoxide (6.55 g, 68.12 mmol) was mixed and purged with N2. Anhydrous toluene (75 mL) was added and the resultant mixture was purged with N2 again. The resultant mixture was heated in an oil bath at 107 0C under N2 for 3 hours. After cooling, the reaction mixture was diluted with DCM (200 mL), washed with H2O (50 mL), and washed with saturated brine (50 mL). The combined organic layers were dried over Na2SO4, concentrated under reduced pressure to give a dark brown liquid. The crude product was purified using a SiO2 gel column, eluting with 5-7percent MeOH in DCM to give 4-[(3i?)-3-methylpiperazin-l-yl]-3-(trifluoromethyl)benzonitrile as a brownish red color oil (l 1.2 g, 76.2percent).

75336-86-6, The synthetic route of 75336-86-6 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; WYETH LLC; WAN, Zhao-Kui; CHENAIL, Eva; IPEK, Manus; LI, Huan-Qiu; MANSOUR, Tarek, Suhayl; SURI, Vipin; XIANG, Jason, Shaoyun; SAIAH, Eddine; WO2010/141550; (2010); A2;,
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.30459-17-7,1-(4-Trifluoromethylphenyl)piperazine,as a common compound, the synthetic route is as follows.

General procedure: 2,6-Dichloro-9-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-9H-purine (24) (447 mg, 1 mmol) was dissolved in 5 mL absolute EtOH, then 1-(alpha,alpha,alpha-trifluoro-p-tolyl)piperazine (0.23g, 1 mmol)/ 2-(1-cyclohexenyl) ethylamine (0.125g, 1 mmol) and (Et)3N (3 equiv) were added. The mixture was refluxed for 10-12 h. The reaction mixture was concentrated in vacuo and the residue was purified by column chromatography. 2-Chloro-6-[4-(4-trifluoromethylphenyl)piperazine-1-yl]-9-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-9H-purine (25) The compound was prepared from (24) and 1-(4-trifluoromethylphenyl)piperazine according to the general procedure and was purified by column chromatography (EtOAc-hexane, 1:2) to yield 25 as viscous oil (850 mg; 75%). 1H NMR (CDCl3) delta 2.0 (s, 3H, CH3), 2.02 (s, 3H, CH3), 2.09 (s, 3H, CH3), 3.44 (br s, 4H, piperazine CH2), 3.94-4.72 (m, 7H, H-4?, CH2-5?, piperazine CH2), 5.55 (t, 1H, H-3?), 5.86 (t, 1H, H-2?), 6.16 (d, 1H, H-1?), 7.09 (d, J = 8.8 Hz, 2H, H-2,6 in phenyl), 7.50 (d, J = 8.4 Hz, 2H, H-3,5 in phenyl), 8.43 (s, 1H, H-8). MS (ESI+) m/e: 641.9 (%100) (M+H), 643.9 (%48) (M+H+2).

30459-17-7, 30459-17-7 1-(4-Trifluoromethylphenyl)piperazine 121718, apiperazines compound, is more and more widely used in various fields.

Reference：
Article; Tuncbilek, Meral; Kucukdumlu, Asl?gul; Guven, Ebru Bilget; Altiparmak, Duygu; Cetin-Atalay, Rengul; Bioorganic and Medicinal Chemistry Letters; vol. 28; 3; (2018); p. 235 – 239;,
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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.

A solution of 2-chloro-N-(2,6-dichlorophenyl)-4-((4- hydroxybutyl)amino)pyrimidine-5-carboxamide (401 mg, 1.03 mmol), tert-butyl 4-(4-aminophenyl)piperazine-1- carboxylate (400 mg, 1.44 mmol) and DIPEA (0.36 mL, 2.06mmol) in anhydrous DMF (7 mL) was stirred at 90C for 60h. The reaction mixture was diluted with EtOAc and water and the layers were separated, the aqueous layer was then extracted once more with EtOAc and the organic layers were combined, washed with water 4 times, dried (MgSO4),filtered and concentrated in vacuo. The residue was purified by flash chromatography (SiC2, 30-70% ethyl acetate in cyclohexane) to afford the title compound (480 mg, 74%) as a brown solid. LCMS (Method A) : = 1.17 mm, m/z = 630 [M+H]., 170911-92-9

The synthetic route of 170911-92-9 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; ALMAC DISCOVERY LIMITED; HARRISON, Timothy; TREVITT, Graham; HEWITT, Peter Robin; O’DOWD, Colin Roderick; BURKAMP, Frank; WILKINSON, Andrew John; SHEPHERD, Steven D.; MIEL, Hugues; WO2015/92431; (2015); A1;,
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115761-79-0, 1-(2,4-Difluorophenyl)piperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Example 24 2-(4-Methylpiperazin-1-yl)ethyl 4-(2,4-difluorophenyl)piperazine-1-carboxylate trihydrochloride 2-(4-Methylpiperazin-1-yl)ethyl 4-nitrophenyl carbonate (Intermediate 4; 680 mg, 2.2 mmol) was dissolved in DMF (20.mL). DIPEA (0.76 mL, 4.4 mmol) and 4-(2,4-difluorophenyl)piperazine (508 mg, 2.2 mmol) were added and the reaction mixture was stirred at room temperature for 24 hours, and the reaction mixture was then concentrated in vacuo. The residue was purified by normal phase column chromatography (eluding with DCM, followed by a 200:8:1 mixture of DCM:EtOH:NH3) followed by reverse phase column chromatography (gradient eluding with MeOH in water, with 1% formic acid in each solvent, 0-100%). The residue was dissolved in DCM (10 mL) and 2M HCl in Et2O (3 mL) was added. The reaction mixture was then concentrated in vacuo to give the title compound 2-(4-methylpiperazin-1-yl)ethyl 4-(2,4-difluorophenyl)piperazine-1-carboxylate trihydrochloride (630 mg, 65%) as a white solid. Analytical HPLC: purity 100% (System A, RT=4.02 min); Analytical LCMS: purity 100% (System A, RT=5.76 min), ES+: 369.5 [MH]+; HRMS calcd for C18H26F2N4O2: 368.2024, found 368.2038.

115761-79-0, The synthetic route of 115761-79-0 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Biovitrum AB; US2009/281087; (2009); A1;,
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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

(S)-4-methyl-5-(oxiran-2-yl)isobenzofuran- 1 (3H)-one (0.75 g, 3.95 mmol)and (S)-tert-butyl 3-(hydroxymethyl)piperazine-1-carboxylate (1.024 g, 4.73 mmol) in ethanol (12 ml) was heated in microwaye at 150 C for 1.5h. The reaction solution was concentrated and the residue was purified on Biotage using 40-100% ethyl acetatelhexane to giye the title compound. LC/MS: (M+1)+: 407.15., 314741-40-7

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

Reference：
Patent; MERCK SHARP & DOHME CORP.; PASTERNAK, Alexander; DE JESUS, Reynalda, Keh; DING, Fa-xiang; DONG, Shuzhi; FRIE, Jessica; GU, Xin; JIANG, Jinlong; SHAHRIPOUR, Aurash; PIO, Barbara; TANG, Haifeng; WALSH, Shawn; WO2014/126944; (2014); A2;,
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59878-57-8, 1-(Cyclopropylcarbonyl)piperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,59878-57-8

To a solution of 2-Fluoro-5-((4-oxo3,4-dihydrophthalazin-l-yl)methyl)benzoic acid (50 mg, 0.168 mmol) in DMA (1 mL) was added DIPEA (56 L, 0.336 mmol) and HBTU (64 mg, 0.170 mmol). The reaction mixture was stirred for 1 hour before addition of cyclopropylpiperazine-l-ylmethanone (0.170 mmol) was carried out. The reaction mixture was stirred at room temperature for 48 h. The reaction mixture was then extracted with DCM (3 x 5 mL) and washed with water (3 x 20 mL). The organic layers were collected, dried with MgS04 and the excess solvent removed in vacuo. Purification via reverse phase HLPC was carried out affording 4-(3-(4 (cyclopropanecarbonyl) piperazine- l-carbonyl)-4- fluorobenzy phthalazin- 1 (2//)-one (olaparib) (25 mg, 34%) as a white solid. *H NMR (400 MHz, CDCh) d = 10.65 (s, 1H), 8.44 – 8.37 (m, 1H), 7.75 – 7.61 (m, 3H), 7.34 – 7.22 (m, 2H), 6.97 (t, J = 8.9 Hz, 1H), 4.22 (s, 2H), 3.90 – 3.09 (m, 8H), 1.79 – 1.52 (s, 3H), 0.99 – 0.88 (m, 2H), 0.81 – 0.63 (s, 2H); {}1^ NMR (376 MHz, CDCb) d = – 117.6; Mp: 69 – 7lC. Data is in accordance with known literature (Menear, K.A., et al., ibid.).

59878-57-8 1-(Cyclopropylcarbonyl)piperazine 2064235, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; OXFORD UNIVERSITY INNOVATION LIMITED; GOUVERNEUR, Veronique; CORNELISSEN, Bart; WILSON, Thomas Charles; (152 pag.)WO2019/186135; (2019); A1;,
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With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.13889-98-0,1-Acetylpiperazine,as a common compound, the synthetic route is as follows.

INTERMEDIATE 19(S)-tert-Butyl 1 -|”2-(4-acetylpiperazin- 1 -yl)-8-methylquinolin-3-yllethylcarbamateIntermediate 9 (150 mg, 0.47 mmol), 1-acetylpiperazine (300 mg, 2.34 mmol), DIPEA (0.42 mL, 2.34 mmol) and NMP (3 mL) were combined in a sealed tube and heated to 1400C for 48 h. After cooling, the reaction mixture was dissolved in a 1 :1 mixture of EtOAc and Et2O (100 mL) and washed with saturated brine (3 x 25 mL). The organic layer was dried (MgSO4) and concentrated in vacuo. Purification by column chromatography (SiO2, 0-100% EtOAc in isohexane) afforded the title compound (151 mg, 78%) as a white solid. LCMS (ES+) 413 (M+H)+.

13889-98-0, As the paragraph descriping shows that 13889-98-0 is playing an increasingly important role.

Reference：
Patent; UCB PHARMA S.A.; ALLEN, Daniel, Rees; BROWN, Julien, Alistair; BUeRLI, Roland; HAUGHAN, Alan, Findlay; LANGHAM, Barry, John; MATTEUCCI, Mizio; OWENS, Andrew, Pate; RAPHY, Gilles; SHARPE, Andrew; WO2010/133836; (2010); A1;,
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With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.848482-93-9,(S)-4-(tert-Butoxycarbonyl)piperazine-2-carboxylic acid,as a common compound, the synthetic route is as follows.,848482-93-9

To a stirred suspension of (S)-4-/V-Boc-piperazine-2-carboxylic acid (502 mg, 2.18 mmol) in water (2.5 mL) was added NaHC03(366.2 mg, 4.36 mmol), and the resulting suspension was stirred at ambient temperature for 30 minutes. A solution of benzyl chloroformate (744 mg, 4.36 mmol) in dioxane (4 mL) was then added and the reaction mixture was stirred at ambient temperature overnight. The reaction mixture was then diluted with water (5 mL) and extracted with EtOAc (2 15 mL). The combined organic layer was washed brine, dried over anhydrous Na2S04, filtered and concentrated under reduced pressure. The remaining residue was then dissolved in DMF (7 mL) and K2CO3 (904 mg, 6.54 mmol) was added. After stirring for 5 minutes, CH3I (928 mg, 6.54 mmol) was added slowly and the resulting mixture was stirred at ambient temperature for 2 h. The reaction was quenched with H2O and extracted with EtOAc (2X 15 mL).The combined organic layer was washed with brine, dried over anhydrous Na2S04, filtered and concentrated under reduced pressure to leave brown oil as the product (800 mg, quant.).1H NMR (400 MHz, CDCI3) delta 7.42 – 7.31 (m, 5H), 5.22 – 5.09 (m, 2H), 4.84 – 4.63 (m, 1 H), 4.63 – 4.47 (m, 1 H), 4.11 – 3.81 (m, 2H), 3.72 (d, J = 22.6 Hz, 3H), 3.32 (s, H), 3.08 (d, J = 13.5 Hz, H), .44 (s, 9H). Mass calculated for (Ci9H26N206+H)+379.2, found 379.1.

The synthetic route of 848482-93-9 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; SIMON FRASER UNIVERSITY; CENTRE FOR DRUG RESEARCH AND DEVELOPMENT; YOUNG, Robert Norman; KUMAR, Nag Sharwan; MANDEL, Alexander Laurence; HSIEH, Tom Han Hsiao; TAN, Jason Samuel; SHIDMOOSSAVEE, Fahimeh S.; JAQUITH, James Brian; DULLAGHAN, Edith Mary; (467 pag.)WO2017/75694; (2017); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics