Heterocyclic Building Blocks-piperazine

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.

Intermediate 5-1 tert-Butyl {2-[2-(4-benzoylpiperazin-1-yl)-2-oxoethyl]-6-methyl-2H-indazol-5-yl}carbamate (0828) (0829) 181 mg (0.59 mmol) of {5-[(tert-butoxycarbonyl)amino]-6-methyl-2H-indazol-2-yl}acetic acid (Intermediate 4-1) and 169 mg (0.89 mmol) of phenyl(piperazin-1-yl)methanone were initially charged in 5 ml of tetrahydrofuran and 0.5 ml of N,N-dimethylformamide 91 mg (0.59 mmol) of 1-hydroxy-1H-benzotriazole hydrate, 227 mg (1.19 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 0.25 ml (1.79 mmol) of triethylamine were added and the mixture was stirred at 25 C. for 18 h. The mixture was diluted with water and ethyl acetate and the precipitated solid was filtered off, washed with water and diethyl ether and dried under reduced pressure. This gave 248 mg (85% of theory) of the title compound. (0830) UPLC-MS (Method A1): Rt=1.07 min (0831) MS (ESIpos): m/z=478 (M+H)+ (0832) 1H NMR (400 MHz, DMSO-d6): delta=1.42 (s, 9H), 2.24 (s, 3H), 3.32-3.82 (m, 8H), 5.41 (br. s., 2H), 7.33 (s, 1H), 7.38-7.48 (m, 5H), 7.52 (s, 1H), 8.12-8.16 (m, 1H), 8.35 (s, 1H).

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

Reference：
Patent; Bayer Pharma Aktiengesellschaft; BOTHE, Ulrich; SIEBENEICHER, Holger; SCHMIDT, Nicole; ROTGERI, Andrea; BOeMER, Ulf; RING, Sven; IRLBACHER, Horst; GUeNTHER, Judith; STEUBER, Holger; LANGE, Martin; SCHAeFER, Martina; (191 pag.)US2016/311833; (2016); A1;,
Piperazine – Wikipedia
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215309-01-6, 3-(4-Methylpiperazin-1-yl)benzoic acid is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Example 41 : lambdaf-{2-cyano-9-[2-(dimethylamino)ethyl]-9Hphiurin-6-yl}-lambdaf <:yclopentyl-3- (4-methyl-1 -piperazinyl)benzohydrazide bis(trifluoroacetate). Intermediate 51 (0.3 g, 1.36 mmol) was suspended in oxalyl chloride (ALDRICH, 1 ml.) and the mixture was stirred at rt for 16 h. Then, dry DCM (4 ml.) was added and after further 8 h, more oxalyl chloride (ALDRICH, 2 mL) and dry DCM (2 mL) were added. These additions were continued until the reaction was complete. Then, solvent was removed in vacuo yielding the corresponding acid chloride. It was then added over a solution of Intermediate 57 (0.1 1 g, 0.37 mmol), potassium te/f-butoxide (ALDRICH, 0.14 g, 1.28 mmol) and DIPEA (FLUKA, 0.08 mL, 0.45 mmol) in dry THF (12 mL). The reaction mixture was stirred at rt and more Intermediate 51 (0.09 g, 0.29 mmol) in dry THF (2 mL) was added in order to drive the reaction to completion. After 2 days, solvent was removed under reduced pressure and the residue partitioned between DCM and sat. NH4CI. The aqueous phase was basified to pH 10 with 2N NaOH and product was extracted with DCM. The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated to dryness. The crude product was purified by preparative HPLC (X-Terra 30×150 mm, ACN:H2O, 0.1%TFA, isocratic 20%, then, re-purified using gradient 20- 60%, and, then, SunFire 19x 150 mm, ACN:H2O, 0.1% TFA, gradient 20- 40%). The product obtained was dissolved in DCM (25 mL) and washed with sat. NaHCO3 (25 mL). The organic layer was washed with brine and then, 4 M HCI in dioxane was added dropwise in order to form the corresponding hydrochloride. It was then purified by preparative HPLC (X-Terra, 3Ox 150 mm, ACN;H2O, 0.1% TFA, isocratic 20%) to give the title compound. 1H NMR (300 MHz, d6-DMSO, 80 0C) delta ppm: 10.86- 10.53 (br., 1 H), 8.48- 8.25 (br., 1 H), 7.56- 7.36 (m, 3H), 7.29- 7.19 (m, 1 H), 6.01- 5.22 (br., 1 H), 4.64- 4.50 (m, 2H), 4.07- 2.91 (br., 10H), 2.88 (s, 3H), 2.81 (s, 6H), 2.07- 1.76 (m, 4H), 1.76- 1.50 (m, 4H). [ES+ MS] m/z 517 (M)+.

215309-01-6, 215309-01-6 3-(4-Methylpiperazin-1-yl)benzoic acid 4741681, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; GLAXO GROUP LIMITED; WO2008/107368; (2008); 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.479353-63-4,1-Boc-4-(4-Carboxybenzyl)piperazine,as a common compound, the synthetic route is as follows.

Example 51 tert-Butyl 4-{4-[({4-[(E,Z)-[(3-bromo-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}amino)carbonyl]benzyl}piperazine-1-carboxylate trifluoroacetate A solution of 3-(4-amino-1,2,5-oxadiazol-3-yl)-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one (30 mg, 88 mumol), 4-{[4-(tert-butoxycarbonyl)piperazin-1-yl]methyl}benzoic acid (84 mg, 0.26 mmol), and 4-dimethylaminopyridine (6.4 mg, 53 mumol) in pyridine (0.75 mL) was treated with phosphoryl chloride (25 muL, 0.27 mmol) dropwise at -15 C. The reaction mixture was heated in a microwave at 100 C. for 5 min. The reaction mixture was concentrated to residue which was rediluted with methanol (1 mL), treated with 2.0 M sodium hydroxide in water (0.3 mL, 0.6 mmol), and stirred for 30 min. The reaction mixture was quenched with acetic acid (50 muL, 0.9 mmol), filtered, and purified by preparative LCMS to give the desired product (29 mg, 45%). LCMS for C26H30BrFN7O5 (M+H)+: m/z=618.0, 620.0.

479353-63-4, 479353-63-4 1-Boc-4-(4-Carboxybenzyl)piperazine 2795516, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; Combs, Andrew P.; Yue, Eddy W.; US2006/258719; (2006); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

75336-86-6, (R)-2-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Example 106: Synthesis of 6-(( R )-4-(4-Cyanophenyl)-2-methylpiperazin-1-yl)- N -(( E )-5-hydroxyadamantan-2-yl)picolinamide [300] [301] Step 1: Synthesis of ( R )-4-(3-methylpiperazin-1-yl)benzonitrile [302] 4-Bromobenzonitrile (200 mg, 1.099 mmol), (R)-2-methylpiperazine (121 mg, 1.209 mmol), Pd2(dba)3 (20 mg, 0.022 mmol), BINAP (41 mg, 0.066 mmol), and sodium-tert-butoxide (211 mg, 2.199 mmol) were suspended in toluene (5 ml), and then the resulting liquid was stirred at 100oC under nitrogen stream for 5 hours. 1N aqueous HCl solution (20 ml) was added to the resulting reaction liquid, followed by extraction with MC (10 ml x 2). The aqueous layer was neutralized by addition of 5N aqueous NaOH solution, followed by extraction with 5percent MeOH/MC (20 ml x 2). The organic layer was dried over anhydrous sodium sulfate, followed by filtration and concentration, and then the residue thus obtained was subjected to MPLC (10percent MeOH/MC), to obtain 152 mg of pale yellow oil (69percent)., 75336-86-6

As the paragraph descriping shows that 75336-86-6 is playing an increasingly important role.

Reference：
Patent; SK Chemicals Co.,Ltd.; RYU, Je Ho; KIM, Shin Ae; RYU, Keun Ho; KIM, Jae Sun; KIM, Nam Ho; HAN, Hye Young; KIM, Yong Hyuk; YOUN, Won-No; LEE, Yoon-Jung; SON, Hyun Joo; LEE, Bong-yong; PARK, Sung Hoon; LEE, Ju Young; LEE, Hyun Jung; JUNG, Hoe Chul; SHIN, Young Ah; LEE, Jung A; LEE, Bo Ram; SA, Joon Ho; WO2011/139107; (2011); 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.21655-48-1,cis-2,6-Dimethylpiperazine,as a common compound, the synthetic route is as follows.

Methyl 8-cyclohexyl-1a[[[3R,5S]-3,5-dimethyl-1-piperizinylycarbonyl]-12-methoxy-1,1a,2,12b-tetrahydrocyclopropa[d]indolo[2,1,-a][2]benzazepine-5-carboxylate. To the 8-cyclohexyl-12-methoxy-5-(methoxycarbonyl)-1,12b-dihydrocyclopropa [d]indolo[2,1-a][2]benzazepine-1a(2H)-carboxylic acid(70 mg, 0.15 mmol) in 1.0 mL of an. DMF in a 3 dram vial equipped with a Teflon lined screw cap was added DIPEA (0.1 mL, 0.57 mmol), 2-(1H-Benzotriazole-1-yl)-1,1,3,3,-Tetramethyluronium Tetrafluoroborate (TBTU, 67 mg, 0.21 mmol) followed by 2,6-dimethyl piperizine (21 mg, 0.18 mmol). The reaction was shaken on an Innova 2000 orbital shaker at 240 rpm overnight at room temperature. The reaction solution was filtered and purified by Prep HPLC (Acetonitrile/water with TFA buffer) to yield the title compound as yellow solid (70 mg, 85percent yield). MS m/e 556 (MH+).

21655-48-1, As the paragraph descriping shows that 21655-48-1 is playing an increasingly important role.

Reference：
Patent; Bristol-Myers Squibb Company; US2007/270406; (2007); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

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 3; Example 3A; 1 -f 2.4-difIuorophenyl)-4-(2-naphthv1sulfonyl)rhoiperazine; Step 3A; To a stirred solution of naphthalene-2-sulfonyl chloride (350 mg, 1.54 mmol) and l-(2,4-difluororhohenyl)piperazine (305.0 mg, 1.54 mmol) in anhydrous dichloromethane (5 mL) was added diisopropylethylamine (0.670 mL, 3.85 mmol). The mixture was stirred for 30 minutes. Reaction was complete as determined by TLC. The reaction mixture was purified via flash column chromatography to afford l-(2,4-difluorophenyl)-4-(2-naphthylsulfonyl)piperazine in 55% yield (327 mg) as white solid.IH NMR (400 MHz, DMSO-D6) delta ppm 3.00 – 3.07 (m, 4 H) 3.07 – 3.15 (m, 4 H) 6.94 – 7.02 (m, 1 H) 7.03 – 7.12 (m, 1 H) 7.12 – 7.21 (m, 1 H) 7.67 – 7.84 (m, 3 H) 8.11 (d, J=8.08 Hz, 1 H) 8.21 (d, J=8.59 Hz, 1 H) 8.25 (d, J=8.08 Hz, 1 H) 8.49 (d, J=I.77 Hz, 1 H). HRMS: calcd for C20H18F2N2O2S + H+, 389.11298; found (ESI-FTMS, [M+H]l+), 389.113. HPLC Method 1: room temperature, 6.658 min, 96.32%, HPLC Method 2: room temperature, 7.312 min, 99.29%., 115761-79-0

As the paragraph descriping shows that 115761-79-0 is playing an increasingly important role.

Reference：
Patent; WYETH; WO2007/92435; (2007); 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.78818-15-2,Benzyl 3-oxopiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.,78818-15-2

Preparation 57; 4-{5-[4-(2-Methoxy-(1S)-methyl-ethoxy)-phenyl]-[1,3,4]oxadiazol-2-ylmethyl}-3- oxo-piperazine-1-carboxvlic acid benzyl ester; A solution of potassium carbonate (136mg, 2. 4mmol) suspended in tetrahydrofuran (3mL) was cooled to 0C. Tetrabutylammonium bromide (130mg, 0. 40mol), 4-benzyloxycarbonyl piperazin-2-one (568mg, 2. 43mmol), and the product of preparation 48 (572mg, 2. 02mmol), were added in tetrahydrofuran (3mL) and the mixture was allowed to warm to room temperature and stir for 18 hours. The solvent was then evaporated under reduced pressure and the residue was dissolved in ethyl acetate and washed with water and brine. The organic phase was dried over magnesium sulfate and concentrated in vacuo to give an oil. Purification by column chromatography on silica gel, eluting with pentane: diethyl ether 90: 10 to 20: 80, gave the title compound as a pale brown foam in 70% yield, (679mg). ‘H NMR (CDCI3, 400MHz) d : 1.40 (d, 3H), 3.40 (s, 3H), 3.50 (m, 1H), 3.55 (t, 2H), 3.60 (m, 1H), 3.80 (t, 2H), 4.15 (s, 2H), 4.64 (m, 1H), 4.90 (s, 2H), 5.15 (s, 2H), 7.00 (d, 2H), 7.40 (m, 5H), 7.95 (d, 2H). MS APCI+ m/z 481 [MH] +

78818-15-2 Benzyl 3-oxopiperazine-1-carboxylate 736777, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; PFIZER LIMITED; PFIZER INC.; WO2005/82866; (2005); A2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

4318-42-7,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.4318-42-7,1-Isopropylpiperazine,as a common compound, the synthetic route is as follows.

[18041 Step 1: Synthesis of methyl4-(((3R.55?)-4-(3-((4-isopropylpiperazin- 1 -yflmethyflbenzyfl-3.5-dimethylpiperazin- 1- yl?)methyflbenzoate[18051 Methyl 4-(((3R,55)-4-(3-formylbenzyl)-3 ,5-dimethylpiperazin- 1 -yl)methyl)benzoate (formula 5-1, 0.200 g, 0.526 mmol) and 1-isopropylpiperazine (0.113 mL, 0.788 mmol) were dissolved in methylene chloride (4 mL), and the solution was stirred at room temperature for 1 hour. Na(OAc)3BH (0.223 g, 1.051 mmol) was added to the solution, followed by stirring at the same temperature for 17 hours. Then, a saturated aqueous solution of sodium hydrogen carbonate was added to the reaction mixture, followed by extraction with methylene chloride. The extract was filtered through a plastic filter to remove solid residue and an aqueous layer, and then concentrated under reduced pressure. The concentrate was purified by column chromatography (silicon dioxide, 4 g cartridge; methanol/methylene chloride = from 0 percent to 10 percent) and concentrated to afford the desired compound (0.225 g, 86.9 percent) as a pale brown oil.

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

Reference：
Patent; CHONG KUN DANG PHARMACEUTICAL CORP.; SONG, Hyeseung; LEE, Changgon; KWAK, Dalyong; LEE, Jaeyoung; BAE, Suyeal; KIM, Yuntae; BAE, Daekwon; HA, Nina; BAE, Miseon; KIM, Jihyun; WO2015/137750; (2015); A1;,
Piperazine – Wikipedia
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: A mixture of carboxylic acid 6 (3.5 mol), EDC*HCl (5.4 mol), HOBt (5.4 mol) in anhydrous DMF (20 mL) was stirred at RT. Substituted piperazine (3.5 mol) was then added and the mixture was further stirred at RT for 10-12 hr40. After completion of the reaction as indicated by TLC, the reaction mixture was quenched in crushed ice. The precipitated solid was washed with NaHCO3 and dil. HCl. The product thus obtained was purified by silica gel column chromatography using hexane: ethyl acetate as eluent., 30459-17-7

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

Reference：
Article; Raundal, Hemant N.; Jadhav, Rahul P.; Patil, Amar A.; Bobade, Vivek D.; Indian Journal of Chemistry – Section B Organic and Medicinal Chemistry; vol. 54B; 8; (2015); p. 979 – 987;,
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.1152367-80-0,(S)-1,3-Dimethylpiperazine,as a common compound, the synthetic route is as follows.

Part A 2-[(2S)-2,4-Dimethyl-1-piperazinyl]-4-pyrimidinamine A mixture of 2-chloro-4-pyrimidinamine (200 mg, 1.544 mmol), Hunig’s base (1348 mul, 7.72 mmol) and (3S)-1,3-dimethylpiperazine (Ref.: WO2009061879 (A1)) (318 mg, 1.698 mmol) in N,N-dimethylformamide (DMF) (1.7 ml) was heated to 220 C. via a microwave reactor for 15 min. The reaction mixture was purified by RP-HPLC to yield 2-[(2S)-2,4-dimethyl-1-piperazinyl]-4-pyrimidinamine (88 mg, 0.425 mmol, 28% yield). MS (ES+) m/z 208.0 (MH+).

1152367-80-0, 1152367-80-0 (S)-1,3-Dimethylpiperazine 13152036, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; GlaxoSmithKline Intellectual Property (No. 2) Limited; Aubart, Kelly M.; Benowitz, Andrew B.; Fang, Yuhong; Hoffman, James; Karpinski, Joseph M.; Knox, Andrew Nicholson; Liao, Xiangmin; Qin, Donghui; Shi, Dongchuan; Spletstoser, Jared T.; US8901119; (2014); B2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics