Heterocyclic Building Blocks-piperazine

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.169447-86-3,(S)-tert-Butyl 2-benzylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

The synthesis of compounds of this embodiment is shown in FIG. 1. As shown, pyridine, quinolines or isoquinolines were coupled with various piperazines through nucleophilic aromatic substitution or Hartwig Buchwald aryl amination., 169447-86-3

As the paragraph descriping shows that 169447-86-3 is playing an increasingly important role.

Reference：
Patent; UNIVERSITY OF SOUTH FLORIDA; YALE UNIVERSITY; WO2008/79945; (2008); A2;,
Piperazine – Wikipedia
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118753-66-5, tert-Butyl 4-aminopiperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To a solution of 1 ,1-dimethylethyl 4-amino-1 -piperazinecarboxylate (270 mg, 1.34 mmol) in DCM-DMF (4:1 , 15 ml_) were added 3-oxo-3,4-dihydro-2H-pyrido[3,2- i?][1 ,4]thiazine-6-carboxylic acid (283 mg, 1.34 mmol), EDC (250 mg, 1.61 mmol) and HOBT (217 mg, 1.61 mmol). After 12h, the solution was concentrated and the residue purified via column chromatography (silica, 1% MeOH in DCM (1% NH4OH)) yielding the title compound as a yellow foam (412 mg, 78 %): LCMS (ES) m/e 394 (M+H)+., 118753-66-5

The synthetic route of 118753-66-5 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; GLAXO GROUP LIMITED; WO2006/20561; (2006); A2;,
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Piperazines – an overview | ScienceDirect Topics

5317-33-9, 3-(4-Methylpiperazin-1-yl)propan-1-ol is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

5317-33-9, To a stirred solution of compound II (6 mg, 0.017 mmol) in THF (2.0 mL) was added 3-(4-methylpiperazin-l-yl)propan-l-ol (5.0 muL, 0.036 mmol), triphenylphosphine (12 mg, 0.043 mmol) and diethyl azodicarboxylate (7.0 muL, 0.043 mmol). After stirring at room temperature for 45 min, the reaction mixture was concentrated. The residue was dissolved in THF/water (3:2, 0.8 mL), passed through a 0.45 mum filter, and purified by HPLC on a Varian Inertsil 5mu ODS-3 (250×100) reverse-phase HPLC column. Elution with 10% to 90% gradient of 0.1% AcOH in water/0.1 % AcOH in CH3CN over 40 min provided compound IV (3.8 mg, 45% yield): LRMS m/z (M+H) calcd for C26H37N2O8 505.2; obsd 505.2.

5317-33-9 3-(4-Methylpiperazin-1-yl)propan-1-ol 79208, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; KOSAN BIOSCIENCES INCORPORATED; WO2006/36941; (2006); 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.6531-38-0,2,2′-(Piperazine-1,4-diyl)diethanamine,as a common compound, the synthetic route is as follows.

To a 25ml RBF containing a magnetic stir bar was added the imidazolide of Bumetanide (0.207g , 0.99mmol) and dissolved in ImI DCM. To the above solution was added the amine (0.172g, 0.999mmol) and let stir overnight at it under argon. TLC in 10% MeOH in EtOAc indicated a very polar spot. Extracted the reaction mixture into EtOAc, washed with water (2x20ml) and then with brine (2x20ml). The organic layer was dried under MgSO4 and filtered. Concentrated the organic layerunder vacuum. Redissolved the crude product in the minimum amount of DCM and reprecipitated from hexanes. Filtered the above precipitate to obtain yellowish white solid. 1HNMR in DMSO-d6+2 drops of MeOD.1HNMR (300MHz, DMSO-d6+2 drops of MeOD) Q.80ppm (t, J=IOHz, 3H),1.1 lppm (m, 2H), 1.37rhopm (m,2H), 2.50ppm (m, 8H), 3.05ppm (t, J= 6.6Hz, 2H), 3.35ppm (t, J=.6Hz, 2H), 4.1ppm (s, br, 4H), 4.95ppm (t, br, IH), 6.85ppm (d, J=7.8Hz, 2H), 7.00ppm (t, 7.2Hz, IH), 7.26ppm (dd, J=7.8Hz, 2H), 7.6ppm (s, IH) 13CNMR (75MHz, DMSO-d6) 19.23, 24.93, 35.89, 47.50, 58.45, 62.50,107.50, 1 19.0, 121.16, 128.0, 134.66, 137.50, 144.0, 143.00, 147.80, 162.20, 171.0 FABMS 519 (M+H)+ calcd m/z for C25H39N6O4S+ 519.28 ; found 519.27, 6531-38-0

6531-38-0 2,2′-(Piperazine-1,4-diyl)diethanamine 81020, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; FLYNN, Gary, A.; YOOL, Andrea, J.; MIGLIATI, Elton, Rodrigues; RITTER, Leslie, S.; WO2008/52190; (2008); A2;,
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Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.196811-66-2,tert-Butyl 4-carbamothioylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

To a solution of 1-tert-butoxycarbonyl-4-thiocarbamoylpiperazine (Reference Example 150) (88mg, 0.35 mmol) in acetonitrile (20 ml) was added 1,2-bis(4-methoxyphenyl)-2-bromo-1-ethanone (Reference Example 14) (117 mg, mmol), and the mixture was stirred at room temperature for 2 hours. The reaction solution was concentrated under a reduced pressure, and the residue was purified by chromatography (silica gel, n-hexane/ethyl acetate) to give a title compound (81 mg, 0.17 mmol, 48%) as a white solid. 1H-NMR (400 MHz, CDCl3) delta: 1.49 (9H, s), 3.47-3.61 (8H, m), 3.79 (3H, s), 3.81 (3H, s), 6.78 (2H, d, J = 8.8 Hz), 6.82 (2H, d, J = 8.8 Hz), 7.21 (2H, d, J = 8.8 Hz), 7.44 (2H, d, J = 8.8 Hz).

196811-66-2, As the paragraph descriping shows that 196811-66-2 is playing an increasingly important role.

Reference：
Patent; TORAY INDUSTRIES, INC.; EP2009006; (2008); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

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

Example 8 2-(2,8-dimethylimidazo[l,2-b]pyridazin-6-yl)-7-[(3S)-3-methylpiperazin-l-yl]pyrido[l,2 a]pyrimidin-4-one 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; 33 mg, 0.107 mmol), and (S)-2-methylpiperazine (43 mg, 0.427 mmol, 4.0 eq.) were stirred in DMSO (2 mL) at 120C overnight. The solvent was removed under high vacuum. The residue was taken up in CH2CI2 and washed with an aqueous saturated solution of NaHC03. The organic layer was separated and dried over Na2S04 and concentrated in vacuo. The crude was purified by column chromatography (S1O2, CH2Cl2/MeOH=95/5 to 90/10) to afford the title product (18 mg, 43%) as a light yellow solid. MS m/z 390.3 [M+H+].

The synthetic route of 74879-18-8 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; PTC THERAPEUTICS INC.; RATNI, Hasane; GREEN, Luke; NARYSHKIN, Nikolai A.; WEETALL, Marla L.; (80 pag.)WO2015/173181; (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.31166-44-6,1-Cbz-Piperazine,as a common compound, the synthetic route is as follows.

To a solution of propylene oxide (4.0 mL, 57 mmol) in DCM (160 mL) was added 2.0M of trimethylaluminum in toluene (27 mL, 54 mmol) at -78 °C under N2. After being stirred at that temperature for 10 min, a solution of benzyl piperazine-l-carboxylate (from Aldrich, 9 mL, 40 mmol) in DCM (60 mL) was added. The resulting reaction mixture was stirred at -78 °C for 30 min. The reaction was then allowed to warm up to 0 °C, stirring for another 30 min. To the reaction mixture was added sodium fluoride (8.2 g, 200 mmol) in one portion, followed by water (5.2 mL, 290 mmol) slowly and periodically at 0 °C. The resulting suspension was rapidly stirred for 1 h at 0 °C and filtered through a short column of Celite and the column was subsequently washed with DCM (120 mL). The combined filtrates were dried over Na2S04, concentrated and purified on silica gel (eluting with 0-10percent MeOH in DCM) to provide the desired product (9.6 g, 76percent). LCMS calculated forCi5H23 203(M+H)+: m/z = 279.2; Found: 279.3. 3/4 NMR (500 MHz, DMSO-d6): delta 7.39-7.31 (5H, m), 8.07 (2H, s), 4.29 (1H, J= 4.0 Hz), 3.75 (1H, m), 3.38 (4H, br s), 2.38 (4H, m), 2.24 (1H, dd, J= 12.5 and 7.0 Hz), 2.17 (1H, dd, J= 12.5 and 7.0 Hz), 1.04 (3H, d, J= 6.0 Hz) ppm.

31166-44-6, As the paragraph descriping shows that 31166-44-6 is playing an increasingly important role.

Reference：
Patent; INCYTE CORPORATION; RODGERS, James, D.; LI, Yun-Long; SHEPARD, Stacey; WANG, Haisheng; WO2011/28685; (2011); A1;,
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Piperazines – an overview | ScienceDirect Topics

1030377-21-9, (S)-1-Boc-2-(Hydroxymethyl)piperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,1030377-21-9

A suspension of 1-fluoro-4-nitrobenzene (1.305 g, 9.25 mmol), (S)-tert-butyl 2-(hydroxymethyl)piperazine-1-carboxylate (2.00 g, 9.25 mmol) and potassium carbonate (1.917 g, 13.87 mmol) in anhydrous DMF (10 mL) was heated to 50 C under a nitrogen atmosphere overnight. The reaction mixture was allowed to cool to room temperature, diluted with water (70 mL) and stirred at roomtemperature for 15 minutes. The precipitated solid was isolated by filtration, washed with water (50 mL), sucked dry and freeze-dried overnight to give the title compound as an orange solid (2.13 g, 68%) . ?H NMR (300 MHz, CDC13) 3 8.11 (dt, 2H), 6.78 (dt, 2H), 4.25 (br s, 1H), 3.85-4.04 (m, 2H), 3.61-3.80 (m, 3H), 3.25-3.43 (m, 2H), 3.18(ddd, 1H), 1.49 (s, 9H). LCMS (Method C): RT = 1.39 mm, m/z = 338 [M+H].

As the paragraph descriping shows that 1030377-21-9 is playing an increasingly important role.

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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Piperazines – an overview | ScienceDirect Topics

30459-17-7, 1-(4-Trifluoromethylphenyl)piperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

General procedure: Synthesis of new compounds 1-4 and 7-9 was performed bynucleophilic substitution (alkylation of amines) following theprocedure previously reported with certain modifications [43].Briefly, the corresponding ferrocene haloalkane (1.0 mmol), thesubstituted amine (1.0 mmol) and K2CO3 or NaH (2.0 mmol) weredissolved in THF (20 mL). The reaction was stirred at room temperatureuntil TLC (CH2Cl2/methanol or hexane/ethyl acetate)proved that the reaction did not go (about 48 h). THF was removedand the residue was diluted in CH2Cl2. The organic phase waswashed with water, dried over anhydrous Na2SO4, filtered, andevaporated. The residue obtained was purified either by automatedflash chromatography, eluting in gradient with CH2Cl2/methanol, orby precipitation with cold diethyl ether. Compounds 5 and 6 werepreviously characterized and evaluated as antibacterial agents [48].So, the general procedure for their synthesis was followed asdescribed by Damljanovic et al. with slight modifications [48]. Amixture of i3 (1.0 mmol), the corresponding amine (1.5 mmol) andMontmorillonite K10 (100 mg) was irradiated by microwave (50W,1.5 min). TLC was used to follow the reaction. The crude wasextracted with CH2Cl2 and evaporated on the rotary evaporator. Theresidue obtained was purified by automated flash chromatography,eluting in gradient with hexane/ethyl acetate. The final compoundwas precipitated with cold diethyl ether in order to obtain an orangepowder.

30459-17-7, The synthetic route of 30459-17-7 has been constantly updated, and we look forward to future research findings.

Reference：
Article; Paucar, Rocio; Martin-Escolano, Ruben; Moreno-Viguri, Elsa; Cirauqui, Nuria; Rodrigues, Carlos Rangel; Marin, Clotilde; Sanchez-Moreno, Manuel; Perez-Silanes, Silvia; Ravera, Mauro; Gabano, Elisabetta; European Journal of Medicinal Chemistry; vol. 163; (2019); p. 569 – 582;,
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.1403898-64-5,(2R,5R)-tert-Butyl 5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

Tert-butyl (2R,5R)-5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate (770 mg, 3.34 mmol), 181 tert-butylchlorodimethylsilane (756 mg, 5.02 mmol), 132 triethylamine (677 mg, 6.69 mmol) and 182 N,N-dimethylpyridin-4-amine (41 mg, 0.33 mmol) were dissolved in 63 DCM (6 ml) and the mixture was stirred at room temperature for 2 hours. The reaction was quenched with saturated 152 aqueous NH4Cl and extracted with DCM (3×30 ml). The organic phase was washed with brine and dried. The solvent was removed under reduced pressure and the crude product was purified by flash chromatography on a silica gel, eluting from 0-30% (57 EtOAc in 148 petroleum ether). The fractions containing the desired product were evaporated to dryness to afford 183 tert-butyl (2R,5R)-5-(((tert-butyldimethylsilyl)oxy)methyl)-2-methylpiperazine-1-carboxylate (1.04 g, 90%) as a colourless oil. 1H NMR (Chloroform-d, 400 MHz) 0.08 (6H, d), 0.91 (9H, s), 1.30 (3H, d), 1.47 (9H, s), 2.56 (1H, dd), 2.96-3.05 (1H, m), 3.10 (1H, dd), 3.30 (1H, dd), 3.55 (1H, dd), 3.68-3.82 (2H, m), 4.15-4.25 (1H, m), (1 exchangeable proton not seen). m/z (ES+), [M+H]+=345., 1403898-64-5

The synthetic route of 1403898-64-5 has been constantly updated, and we look forward to future research findings.

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