Heterocyclic Building Blocks-piperazine

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.150407-69-5,(S)-1-((Benzyloxy)carbonyl)-4-(tert-butoxycarbonyl)piperazine-2-carboxylic acid,as a common compound, the synthetic route is as follows.

Step A – Preparation of Int Int 48-1 To a solution of piperazine carboxylic acid (10 g, 27 mmol) in DCM (50 mL) was added TEA (2.39 mL, 54 mmol) and HATU (11.4 g, 30 mmol) with stirring. The reaction mixture was stirred at room temperature for 30 mins then treated with piperidine (2.57 g, 30 mmol). The reaction solution was stirred for 48 hrs then concentrated. The residue was purified by column chromatography on silica gel eluted with petroleum ether / EtOAc (3 : 1) to afford compound Int 48-1 as yellow oil (10.7g). MS-ESI (m/z): 432 (M+l)+ R 0.6 (PE : EtOAc= 1 : 1) H NMR (CDC13) delta: 7.30-7.24 (m, 5H), 5.25 (s, 1H), 5.14 (d, J=12.3 Hz, 1H), 5.06-4.98 (m, 1H), 4.18-3.80 (m, 5H), 3.41 (s, 2H), 3.21 (d, J=13 Hz, 3H), 1.61 (s, 2H), 1.52 (t, J7=16.6 Hz,, 150407-69-5

As the paragraph descriping shows that 150407-69-5 is playing an increasingly important role.

Reference：
Patent; MERCK SHARP & DOHME CORP.; COBURN, Craig, A.; MALETIC, Milana, M.; LUO, Yunfu; QI, Zhiqi; YU, Tingting; SOLL, Richard; WO2015/73310; (2015); A1;,
Piperazine – Wikipedia
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106261-48-7, 4-((4-Methylpiperazin-1-yl)methyl)benzoic acid is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

General procedure: The mixture containing compound 6 (2.51 mmol), methanol (5.0 mL), 2 M NaOH (1.6 mL) was stirred at room temperature for 4 h, concentrated under reduced pressure and acidified with concentrated hydrochloric acid to pH 2. The aqueous phase was concentrated to dryness under reduced pressure to afford the crude 4-aminomethylbenzoic acid (containing sodium chloride) which was carried on the next step without further purification. The 4-aminomethylbenzoic acid (2.51 mmol) and 2 drops of DMF were added to thionyl chloride (10 mL). The mixture was refluxed for2 h. The volatile was removed under reduced pressure to give a pale yellow solid which was then dissolved in anhydrous THF (10 mL) and was added dropwise to a suspension of sodium azide (0.24 g, 3.77 mmol) in 10 mL of THF/H2O (4:1, v/v) at 0-5C. Then the mixture was stirred at room temperature overnight and THF was removed under reduced pressure. The aqueous phase was extracted with dichloromethane (20 mL 3). The organic layerwas combined, washed with brine (20 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to produce compounds 7a-7f as yellow or brown oil., 106261-48-7

Big data shows that 106261-48-7 is playing an increasingly important role.

Reference：
Article; Zuo, Sai-Jie; Zhang, Sai; Mao, Shuai; Xie, Xiao-Xiao; Xiao, Xue; Xin, Min-Hnag; Xuan, Wei; He, Yuan-Yuan; Cao, Yong-Xiao; Zhang, San-Qi; Bioorganic and Medicinal Chemistry; vol. 24; 2; (2016); p. 179 – 190;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

106261-48-7, 4-((4-Methylpiperazin-1-yl)methyl)benzoic acid is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Example 12: 4-( 4-Methvl-piperazin-1-vlmethvl)-N-r 4-(5-thiophen-3-vl-pvrimidin-2-vlamino )-phenvll- benzamide; 4-Chloromethylbenzoic acid (1.7 g, 10 mmol) and 2.78 mL (20 mmol) of triethylamine in 50 mL of dimethylformamide was stirred with 1.22 mL (11 mmol) of N-methylpiperazine overnight at room temperature. The white solid was collected by vacuum filtration and washed with dichloromethane. The combined filtrates were rotary evaporated to dryness to give 4-(4-methyl-piperazin-1-ylmethyl)-benzoic acid. N-(5-Thiophen-3-yl-pyrimidin-2-yl)-benzene-1 ,4-diamine (55 mg, 0.20 mmol), triethylamine (0.112 mL, 0.80 mmol), BOP reagent (265 mg, 0.6 mmol) and 93 mg (0.4 mmol) of 4-(4-methyl-piperazin-1- ylmethyl) -benzoic acid in 1 mL of dimethylformamide were stirred overnight at room temperature. The solvent was evaporated and the residue purified by flash chromatography eluting with dichloromethane:methanol 20: 1 and then dichlormehane:methanol 15: 1 to give 4-(4-methyl-piperazin-1- ylmethyl)-N[4-(5-thiophen-3-yl-pyrimidin-2-ylamino)-phenyl]-benzamide. H-NMR (dimethylsulfoxide-d6) 8 10.03 (s, 1 H), 9.65 (s, 1 H), 8.80 (s, 2H), 7.85 (m, 3H), 7.67 (m, 2H), 7.63 (m, 2H), 7.57 (d, 1 H), 7.38 (d, 2H), 3.45 (s, 2H), 2.50 (m, 8H), 2.30 (s, 3H). MS (m/z) 485 [M+1]., 106261-48-7

As the paragraph descriping shows that 106261-48-7 is playing an increasingly important role.

Reference：
Patent; SUGEN, INC.; WO2005/113548; (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.142-64-3,Piperazine Dihydrochloride,as a common compound, the synthetic route is as follows.

217 mg (1 mmol) of alkaloid and 183 mg (1.5 mmol)Monopiperazine hydrochloride was added to 10 mL of methanol and 62 mg (0.1 mmol)In the mixed system of Yb(OTf)3, the reaction was stirred at room temperature for 3 days, and the reaction was completed by TLC.Add 100 mg (1.2 mmol) of NaHCO3 powder and continue to stir for 12 h.Concentrate to dryness under reduced pressure and add 10 mL of benzene to residue.After stirring for 10 min, it was quickly demineralized by a neutral Al2O3 column, concentrated, and purified by silica gel column chromatography (benzene: acetone: ammonia = 10:1:2) to obtain intermediate (III) in a yield of 79%.

142-64-3, As the paragraph descriping shows that 142-64-3 is playing an increasingly important role.

Reference：
Patent; Shijiazhuang College; Zhang Baohua; Shi Lanxiang; (8 pag.)CN109776575; (2019); A;,
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Piperazines – an overview | ScienceDirect Topics

4318-42-7,4318-42-7, 1-Isopropylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

General procedure: In an oven-dried RB flask, compound 6c (250mg, 1.01mmol) and formaldehyde solution, 37?41wt.percent in water (0.15mL, 2.02mmol) were mixed in glacial acetic acid (5mL). Morpholine (220.4mg, 2.53mmol) was added drop wise at 0°C. The resulting mixture was stirred at room temperature for 12h. After completion of the reaction, the excess solvent was evaporated to dryness under reduced pressure. The residue was neutralized with 10percent NaHCO3 solution, the solid formed was collected by filtration, washed with water and dried. The crude product was purified by silica gel column chromatography to provide title compound.

As the paragraph descriping shows that 4318-42-7 is playing an increasingly important role.

Reference：
Article; Jose, Gilish; Kumara, T. H. Suresha; Nagendrappa, Gopalpur; Sowmya; Jasinski, Jerry P.; Millikan, Sean P.; More, Sunil S.; Janardhan, Bhavya; Harish; Chandrika; Journal of Molecular Structure; vol. 1081; (2015); p. 85 – 95;,
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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

b. 7-[3-(4-Methyl-piperazin-1-yl)-propoxy]-4-piperidin-4-yl-quinazoline; Solid KOtBu (1.36 g, 12.1 mmol) was added in one portion under air to a homogeneous solution of 4-(7-Fluoro-quinazolin-4-yl)-piperidine-1-carboxylic acid tert-butyl ester (3.33 g, 10.1 mmol), as prepared in the preceding step, and commercial 3-(4-methyl-piperazin-1-yl)-propan-1-ol (1.50 g, 9.50 mmol) in dry THF (10 mL), while stirring on an ice bath. Following KOtBu addition, the ice bath was immediately removed, and the resulting homogeneous amber solution was stirred for 6 hr. 6 M aqueous HCl (10 mL, 60 mmol) was then added in one portion, and the reaction was stirred overnight (mild bubbles were seen following HCl addition, but these subsided after 15 min). The reaction was then partitioned with 9:1 DCM/MeOH (50 mL) and 2.5 M NaOH (28 mL, 70 mmol), and the aqueous layer was extracted with 9:1 DCM/MeOH (1×50 mL). The combined organic layers were dried (Na2SO4) and concentrated by rotary evaporation at 90 C. to provide the crude title compound as a clear yellow oil (3.79 g, ?102%? crude yield). LC/MS (ESI): calcd mass 369.3, found 370.2 (MH)+.

The synthetic route of 5317-33-9 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Baindur, Nand; Gaul, Michael David; Kreutter, Kevin Douglas; Baumann, Christian Andrew; Kim, Alexander J.; Xu, Guozhang; Tuman, Robert W.; Johnson, Dana L.; US2006/281772; (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.169447-86-3,(S)-tert-Butyl 2-benzylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

Step A: Amination of halopyrazine; Preparation of 2-amino-5-bromo-3-r(S)-4-Boc-3-benzylpiperazinyllpyrazine 108; To a solution of 2-arnino-3,5-dibromopyrazine 106 (0.2 g, 0.79 mmol.) and (S)- 1 -Boc-2-benzylpiperazine 107 (0.44 g, 1.59 mmol) in dioxane (2 ml_) and trifluoromethylbenzene (2 ml_) was added diisopropylethylamine (0.31 g, 2.4 mmol). The reaction mixture was heated in a microwave reactor at 210 0C for 20 minutes. Ethyl acetate (100 ml_) was added. The organic layer was washed with water and brine. The organic layer was dried over sodium sulfate. The organic solvent was evaporated under reduced pressure. The crude product was purified by RP-HPLC to yield the desired 2-amino-5-bromo-3-[(S)-4-Boc-3-benzylpiperazinyl]pyrazine 108 (0.24 g, 0.536 mmol).

169447-86-3, 169447-86-3 (S)-tert-Butyl 2-benzylpiperazine-1-carboxylate 17750441, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; SCHERING CORPORATION; WO2007/126964; (2007); A2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

196811-66-2, tert-Butyl 4-carbamothioylpiperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To a stirred solution of tert-butyl 4-carbamothioylpiperazine-1-carboxylate (synthesized according to Example 5, Step 1, 1.3g, 5.3 mmol) in dioxane (10 mL), TEA(1 mL, 7 mmol) and 1-bromo-3,3-dimethylbutan-2-one (0.94 mL, 6.8 mmol) were added at rt and stirred for 16 h at 90 C. The completion of the reaction was monitored by TLC. Thereaction mixture was quenched with water and extracted with EtOAc. The organic layer was dried over anhydrous Na2504, concentrated under vacuum and the resulting crude product was taken as such for next step without further purification. Yield: 88% (1.5 g, black liquid). LCMS: (Method A) 326.2 (M+H), Rt. 3.75 mm, 60.4% (Max)., 196811-66-2

196811-66-2 tert-Butyl 4-carbamothioylpiperazine-1-carboxylate 12093220, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; ASCENEURON S. A.; QUATTROPANI, Anna; KULKARNI, Santosh, S.; GIRI, Awadut Gajendra; TORONTO, Dawn, V.; CROWE, David, Malcolm; (150 pag.)WO2017/144637; (2017); A1;,
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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

Sodium hydride (60percent in mineral oil; 43.56 g; 1089 mmol) was added to a 3L reaction flask under nitrogen. A mechanical stirrer and thermocouple was attached. Dry diglyme (400 mL) was added. A solution of 2-(4-methylpiperazin-l-yl)ethanol (157 g; 1089 mmol) in diglyme (450 mL) was added slowly with stirring. The mixture was stirred with warming to 40 °C for 1 hour. 4-Chloropyridin-2-amine (70.0 g; 544.5 mmol) was added as a solid. The mixture was heated to 80 °C with stirring until effervescence had ceased. The temperature was increased to 157 °C for 16 hours. The mixture was allowed to cool and diluted with water (500 mL). THF (1000 mL) was added followed by sodium chloride (sufficient to saturate the aqueous phase). The phases were separated and the aqueous phase was further extracted with THF (3 x 800 mL). Additional water was added as required to aid in phase separation. The combined organic phases were dried with sodium sulfate (1000 g) for 16 hours and filtered. The solvent was removed under vacuum to remove the majority of the THF. The solution was filtered through Celite.(R). to remove fine particulates rinsing with diglyme. The diglyme was removed under vacuum (10 mm Hg vacuum, with the bath temperature increased to 60 °C). The residue was placed under high vacuum for 1 hour and then triturated with ether (400 mL). The resulting solids were collected by filtration, washed with ether and dried under vacuum to give the product (100.4 g) as an off white solid.

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

Reference：
Patent; ARRAY BIOPHARMA INC.; BOYS, Mark Laurence; BRADLEY, Michael; DELISLE, Robert Kirk; HENNINGS, D. David; KENNEDY, April L.; MARMSATER, Fredrik P.; MEDINA, Matthew; MUNSON, Mark C.; RAST, Bryson; RIZZI, James P.; RODRIGUEZ, Martha E.; TOPALOV, George T.; ZHAO, Qian; WO2011/79076; (2011); A1;,
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Piperazines – an overview | ScienceDirect Topics

129799-15-1, Methyl 1-Boc-piperazine-2-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To a mixture of 1-tert-butyl 2-methyl piperazine- 1,2-dicarboxylate (5.0 g, 22.6 mmol, 1.00 eq) in MeOH (50.0 mL) was added HCl/dioxane (4.0 M, 134 mL). The reaction mixture was degassed and purged with nitrogen 3 times, and the mixture was stirred at 25 C for 12 hours under a nitrogen atmosphere. The reaction mixture was concentrated under reduced pressure to dryness to give methyl piperazine- 2-carboxylate (4.89 g, 2HC1, crude) as a white solid, which was used directly in the next step without further purification.

129799-15-1, 129799-15-1 Methyl 1-Boc-piperazine-2-carboxylate 2756818, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; MIRATI THERAPEUTICS, INC.; ARRAY BIOPHARMA, INC.; FISCHER, John, P.; FELL, Jay, Bradford; BLAKE, James, F.; HINKLIN, Ronald, Jay; MEJIA, Macedonio, J.; HICKEN, Erik, James; CHICARELLI, Mark, Joseph; GAUDINO, John, J.; VIGERS, Guy, P.A.; BURGESS, Laurence, E.; MARX, Matthew, Arnold; CHRISTENSEN, James, Gail; LEE, Matthew, Randolf; SAVECHENKOV, Pavel; ZECCA, Henry, J.; (529 pag.)WO2017/201161; (2017); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics