Heterocyclic Building Blocks-piperazine

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.

Example 12[4-(3,3-Bis-{4-[3-(4-acetyl-piperazin-1-yl)-prop-1-ynyl]-phenyl}allylsulfanyl)-2-methylphenoxy]acetic acidA mixture of 1-piperazin-1-yl-ethanone (15.2 g, 0.119 mol; prepared as described in U.S. Pat. No. 2,973,362), 3-bromopropyne (17 g, 0.143 mol) and potassium carbonate anhydrous (21.5 g, 0.156 mol) in 2-butanone (150 mL) was refluxed for 6 h. A separated solid was filtered off, washed with 2-butanone (80 mL) and 2-butanone was evaporated in vacuo. The residue was purified by vacuum distillation to yield 1-(4-prop-2-ynylpiperazin-1-yl)ethanone, b.p. 115 C./7 Torr).Yield: 12.2 g (62%).M.p. 63-65 C.

13889-98-0, 13889-98-0 1-Acetylpiperazine 83795, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; Novo Nordisk A/S; High Point Phamaceticals LLC; US2011/39841; (2011); A1;,
Piperazine – Wikipedia
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5625-67-2, Piperazin-2-one is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,5625-67-2

To a stirred solution of W-1 (20.0 g, 0.200 mol) in DCM, is added Boc anhydride (43.6 g, 0.200 mol), and TEA (40.4 g, 0.400 mol). The mixture is stirred at about 25 C. for about 18 hours. The mixture is concentrated and the residue dissolved in EtOAc then extracted with water. The organic layer is concentrated and the residue is purified by silica gel chromatography to give W-2.

The synthetic route of 5625-67-2 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Boehringer Ingelheim International GmbH; BYLOCK, Lars Anders; US2013/236468; (2013); 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.21655-48-1,cis-2,6-Dimethylpiperazine,as a common compound, the synthetic route is as follows.

To a solution of czs-2,6-dimethylpiperazine (1.00 g, 8.70 mmol) in CHC13 (20 mL) was added Boc anhydride (1.90 g, 8.70 mmol) drop-wise at 0 C, and the reaction mixture was stirred at room temperature for 16 h. The reaction mixture was diluted with DCM (30 mL) and washed with H20 (30 mL). The organic layer was separated, washed with brine (10 mL), dried over anhydrous Na2S04 and concentrated in vacuo to afford tert-butyl cz5-3,5-dimethylpiperazine-l- carboxylate (1.82 g crude) as an off-white solid. This compound was used as such for the next reaction without further purification. LC/MS (ESI) m/e [M+H]+/RT (min)/%: (0321) 215.00/2.52/83.4%. 1H NMR (400 MHz, DMSO-d6) delta 1.05 (d, J = 6.1 Hz, 6H), 1.20 (d, J = 6.7 Hz, 1H), 1.46 (s, 9H), 2.32-2.40 (m, 2H), 2.72-2.82 (m, 2H), 3.80-4.02 (m, 2H)., 21655-48-1

21655-48-1 cis-2,6-Dimethylpiperazine 6950261, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; NEUROPORE THERAPIES, INC.; WRASIDLO, Wolfgang; STOCKING, Emily, M.; HALL, Adrian; MACCOSS, Malcolm; (139 pag.)WO2017/20010; (2017); A1;,
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Piperazines – an overview | ScienceDirect Topics

78551-60-7,78551-60-7, tert-Butyl 4-benzyl-3-oxopiperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To a solution of diisopropylamine (667 mg, 6.59 mmol) in THF (5 ml) in a dryice-acetone bath was added 1.6 M butyllithium in hexanes (4.13 ml, 6.61 mmol).After 5 min the mixture was put in an ice-water bath and stirred for 20 min. Thesolution was cooled in the dry ice-acetone bath again and a solution of the product ofPreparative Example 1, Step 8 (1.74 g, 5.99 mmol) in THF (20 ml) was added. Themixture was stirred for 1 h. A solution of the above aldehyde in THF (30 ml) wasadded and the mixture was allowed to warm up to RT slowly and stirred for 16 h. Thereaction was quenched with saturated NH4CI (20 ml) and extracted with ether (3x100ml). The combined organic layer was washed with 5% citric acid, saturated NaHCO3,and brine, dried (Na2SO4), concentrated, and purified by column chromatography(gradient EtOAc/Hexanes 0-40%) to give the product (1.20 g, 35%). MS m/e 694

78551-60-7 tert-Butyl 4-benzyl-3-oxopiperazine-1-carboxylate 10891590, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; SCHERING CORPORATION; WO2006/14944; (2006); 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.192130-34-0,tert-Butyl 4-(2-aminoethyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

Preparation 20 tert-butyl 4-(2-{[(6′-{2-cyano-4-[(1,2,4-thiadiazol-5-ylamino)sulfonyl]phenoxy}-1,1′:3′,1″-terphenyl-3-yl)carbonyl]amino}ethyl)piperazine-1-carboxylate To a solution of 6′-{2-cyano-4-[(1 ,2,4-thiadiazol-5-ylamino)sulfonyl]phenoxy}-1 , 1′:3′, 1″- terphenyl-3-carboxylic acid (Preparation 21 , 100 mg, 0.18 mmol) in dimethylformamide (2.0 mL) was added 1 , T-carbonylbis(1 H-imidazole) (38 mg, 0.23 mmol) and N-ethyl-N- isopropylpropan-2-amine (35 mg, 0.27 mmol). The mixture was stirred at room temperature for 30 minutes, then tert-butyl 4-(2-aminoethyl)piperazine-1 -carboxylate (41.3 mg, 0.18 mmol) was added. The resulting reaction was stirred at room temperature for 3 days. The mixture was concentrated in vacuo to provide the title compound as an orange gum (204 mg, >100percent). This material was used in the next step without further purification. LCMS Rt = 2.40 minutes MS m/z 764 [M-H]”, 192130-34-0

The synthetic route of 192130-34-0 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; PFIZER INC.; SWAIN, Nigel Alan; BROWN, Alan Daniel; JONES, Lyn Howard; MARRON, Brian Edward; RAWSON, David James; RYCKMANS, Thomas; STORER, Robert Ian; WEST, Christopher William; WO2015/181797; (2015); A1;,
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129799-08-2, 1-tert-Butyl 3-methyl piperazine-1,3-dicarboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

A mixture of 7-benzyl-2,4-dichloro-6,8-dihydro-5H-pyrido[3,4-d] pyrimidine (3.00 g, 10.2 mmol, 1.00 eq), 1-tert-butyl-3-methyl piperazine-1,3-dicarboxylate (2.62 g, 10.7 mmol, 1.05 eq), DIEA (3.30 g, 25.5 mmol, 4.45 mL, 2.50 eq) in DMSO (50.0 mL) was degassed and purged with nitrogen 3 times. The mixture was stirred at 100° C. for 12 hours under a nitrogen atmosphere. The reaction mixture was diluted with DCM (200 mL), washed with brine (3 50 mL), dried over Na 2SO 4, filtered and concentrated under reduced pressure to dryness. The residue was purified by column chromatography (SiO 2, Petroleum ether/Ethyl acetate=10:1 to 3:1) to give 1-tert-butyl 3-methyl 4-(7-benzyl-2-chloro-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)pipera- zine-1,3-dicarboxylate (2.10 g, 3.81 mmol, 37.4% yield, 91.0% purity) as a yellow oil. ESI MS m/z 502.1 [M+H] +.

129799-08-2, As the paragraph descriping shows that 129799-08-2 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

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.161357-89-7,1-(Methylsulfonyl)piperazine hydrochloride,as a common compound, the synthetic route is as follows.

4-[5-(4-Methanesulfonyl-piperazin-1 -yl)-2-methyl-2,3-dihydro-furo[2,3-clpyridin-2-yl1- piperidine-1 -carboxylic acid tert-butyl ester4-(5-Chloro-2-methyl-2,3-dihydro-furo[2,3-c]pyridin-2-yl)-piperidine-1 -carboxylic acid tert-butyl ester (100 mg) is added to a mixture of 1 -(methylsulfonyl)piperazine hydrochloride (70 mg), Pd2(dba)3 (65 mg), Xantphos (123 mg), and potassium tert- butylate (75 mg) in toluene (4 mL) under an argon atmosphere. The reaction mixture is stirred in an oil bath at 105C over night. After cooling to room temperature water is added and the mixture is extracted with ethyl acetate. The combined extracts are concentrated in vacuo and the residue is chromatographed on silica gel(cyclohexane/ethyl acetate 50:50? 0: 100) to give the title compound. LC (method 1 1 ): tR = 1 .03 min; Mass spectrum (EST): m/z = 481 [M+H]+.

161357-89-7, As the paragraph descriping shows that 161357-89-7 is playing an increasingly important role.

Reference：
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; HIMMELSBACH, Frank; ECKHARDT, Matthias; HEINE, Niklas; LANGKOPF, Elke; NOSSE, Bernd; WO2012/80476; (2012); A1;,
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Piperazines – an overview | ScienceDirect Topics

109384-27-2, 1-Methylpiperazin-2-one hydrochloride is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

EXAMPLE 325 : 4-(4-methoxy-3-(6-(trifluoromethyl)- lH-indazol-4-yl)benzoyl)- 1 – methylpiperazin-2-one [0942] To a vial containing l-methylpiperazin-2-one HC1 (0.172 g, 1.142 mmol) in dioxane (5 mL) was added trimethylaluminum (0.571 mL, 1.142 mmol) in toluene dropwise at room temperature. After stirring for 15 minutes at room temperature, methyl 4-methoxy-3-(6- (trifluoromethyl)-lH-indazol-4-yl)benzoate (0.1 g, 0.285 mmol) was added. The mixture was heated at 110C for 1 hour in a microwave reactor and was subsequently transferred to a round bottom flask. The reaction mixture was quenched with concentrated HC1 and concentrated. The crude residue was purified by preparative HPLC, eluting with 35% acetonitrile (containing 0.035% TFA) in H20 (containing 0.05% TFA) over a period of 5 minutes. The product-containing fractions were combined and the volatiles removed in vacuo to give a TFA salt of the title compound as light brown semisolid (0.024 g, 19%). 1H NMR (400 MHz, DMSO-<) delta ppm 2.86 (s, 3 H), 3.37 (t, J=5.43 Hz, 2 H), 3.70-3.86 (m, 5 H), 4.12 (s, 2 H), 7.29 (d, J=8.59 Hz, 1 H), 7.37 (d, J=1.01 Hz, 1 H), 7.52 (d, J=2.02 Hz, 1 H), 7.61 (dd, J=8.59, 2.27 Hz, 1 H), 7.94 (s, 1 H), 7.99 (d, J=0.76 Hz, 1 H); ESI-MS m/z [M+H]+ calc'd for C2iHi9F3N403, 433.1; found 433.22., 109384-27-2

109384-27-2 1-Methylpiperazin-2-one hydrochloride 17060766, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; TAKEDA PHARMACEUTICAL COMPANY LIMITED; CHERUVALLATH, Zacharia; ERICKSON, Philip; FENG, Jun; KOMANDLA, Mallareddy; LAWSON, John David; MCBRIDE, Christopher; MIURA, Joanne; MURPHY, Sean; TANG, Mingnam; TON-NU, Huong-Thu; WO2013/130855; (2013); 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

To a stirred solution of X (0.120 g, 0.33 mmol), V (0.090 g, 0.33 mmol) added HATU (0.255 g,0.67 mmol) and DIPEA (0.2 mL, 1.08 mmol) in DMF (2 mL). Reaction was allowed to stir at RT for 24 h.After completion of reaction, reaction mixture was diluted with water and extracted with ethyl acetate (15mL x 3). Brine washing was given to the organic layer and dried over anhydrous Na2SO4. Organic layerwas concentrated under vacuum to obtain crude which was purified by using reverse phase HPLC to obtain5 (0.021 g, 10%).LCMS: 613 [M+1]+1HNMR (400 MHz, DMSO) delta10.4 (s, 1H), 10.6 (s, 1H), 8.3 (s, 1H), 8.2 (d, 2H), 8.1 (d, 1H), 7.9 (t, 3H),7.8 (d, 1H), 7.7 (d, 1H), 7.6 (m, 3H), 7.2 (t, 1H), 3.6 (s, 2H), 2.3 (m, 8H), 2.1 (s, 3H).

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

Reference：
Article; Ramachandran, Sreekanth A.; Jadhavar, Pradeep S.; Miglani, Sandeep K.; Singh, Manvendra P.; Kalane, Deepak P.; Agarwal, Anil K.; Sathe, Balaji D.; Mukherjee, Kakoli; Gupta, Ashu; Haldar, Srijan; Raja, Mohd; Singh, Siddhartha; Pham, Son M.; Chakravarty, Sarvajit; Quinn, Kevin; Belmar, Sebastian; Alfaro, Ivan E.; Higgs, Christopher; Bernales, Sebastian; Herrera, Francisco J.; Rai, Roopa; Bioorganic and Medicinal Chemistry Letters; vol. 27; 10; (2017); p. 2153 – 2160;,
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 5-amino-3,6-dichloro-l,2,4-triazine (253.3 mg, 1.535 mmol), diisopropylethylamine (2.0 mL, 1 1.48 mmol), (S)-tert-butyl 2-(3- (hydroxymethyl)piperazin-l-yl)acetate (410.9 mg, 1.731 mmol) in dioxane (2 mL). The mixture was heated at 120 C for 5 h using microwave. The mixture was concentrated to remove all of solvent. The residue was dissolved in dichloromethane, washed with aqueous sodium bicarbonate solution. The organic solution was separated. The aqueous solution was mixed with brine, extracted with dichloromethane (2 x 35 mL). The combined organic solution was dried over anhydrous sodium sulfate, concentrated to afford a residue. The residue was dissolved into small amount of dichloromethane, filtered. The solid was collected the first batch of product. The solution was purified with flash column chromatography on silica using 1-10% methanol in dichloromethane to afford another batch of product. The product was slight yellow solid (343 mg) and the yield was 65%. NMR (500 MHz, Chloroform-d) delta 5.26 (br, 2H), 4.76 (s, lH), 4.43 (d, J = 13.3 Hz, lH), 4.23 – 3.92 (s, 2H), 3.65 (m, 2H), 3.16 – 2.90 (s, 4H), 1.47 (s, 9H). MS for Ci3H21ClN603: 345.0 (MH+)., 314741-40-7

As the paragraph descriping shows that 314741-40-7 is playing an increasingly important role.

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;,
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