Heterocyclic Building Blocks-piperazine

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.109-07-9,2-Methylpiperazine,as a common compound, the synthetic route is as follows.

[Referential Example 82]; 3-Methylpiperazine-1-carboxylic acid tert-butyl ester; [] 2-Methylpiperazine (3.19 g) was added to 2-(tert-butylcarbonyloxyimino)-2-phenylacetonitrile (7.87 g) in tetrahydrofuran (100 mL) at 0C, followed by stirring for 2 hours. The residue obtained by removal through evaporation of the reaction solvent under reduced pressure was purified through silica gel column chromatography (chloroform – 7N ammonia/methanol mixture), to thereby give the title compound as an oily product (5.70 g, 89%).1H-NMR(400MHz,CDCl3)delta: 1.05(3H,d,J=6.4Hz), 1.46(9H,s), 2.40(1H,br), 2.65-2.84(3H,m), 2.90-3.00(1H,br), 3.94(2H,br). MS(ESI)m/z: 201(M+H)+.

109-07-9, The synthetic route of 109-07-9 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; DAIICHI PHARMACEUTICAL CO., LTD.; EP1591443; (2005); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

122323-88-0, Methyl piperazine-2-carboxylate dihydrochloride is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Reference Example 16 A solution of di-tert-butyl dicarbonate (5.0 g) in dichloromethane (30 ml) is added dropwise, taking one hour at 0 C while stirring, to a mixture of methyl piperazine-2-carboxylate dihydrochloride (5.0 g), triethylamine (7 g) and dichloromethane (70 ml). The reaction mixture is poured into ice-water and extracted with dichloromethane. The organic layer is washed with water and dried, then the solvent is distilled off under reduced pressure. The residue is purified by means of a silica gel column chromatography (eluent, dichloromethane:acetone:ethanol = 5:5:1) to afford methyl 4-tert-butoxycarbonylpiperazine-2-carboxylate as a colorless oily product (4.9 g)., 122323-88-0

As the paragraph descriping shows that 122323-88-0 is playing an increasingly important role.

Reference£º
Patent; Takeda Chemical Industries, Ltd.; EP368670; (1990); 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.,21655-48-1

To a solution of 4-(trifluoromethoxy)-benzaldehyde (776 uL, 4.38 mmol) in methylene chloride (30 mL) was added cis-2,6-dimethyl piperazine (1.0 g, 8.77 mmol). After 1 hour sodium triacetoxy borohydride (2.45 g, 8.77 mmol) was added to the mixture. The solution was stirred at room temperature for an additional 4 hours. The reaction was concentrated in vacuo, diluted with ethyl acetate and extracted with 1N HCl (2*50 mL). The aqueous layer was then neutralized with NaOH and extracted with ethyl acetate (3*50 mL). The organic layer was dried (Na2SO4) and concentrated to provide cis-3,5-dimethyl-1-(4-trifluoromethoxy-benzyl)-piperazine (1.01 g, 80percent). 1H NMR (400 MHz, CD3OD) delta 7.42 (d, 2H), 7.23 (d, 2H), 3.54 (s, 2H), 2.98-2.88 (m, 2H), 2.82-2.74 (m, 2H), 1.69 (t, 2H), 1.05 (d, 6H); LCMS 289.5 (M+1)+.

The synthetic route of 21655-48-1 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; KALYPSYS, INC.; US2007/249519; (2007); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

300543-56-0, (R)-1-((4-Chlorophenyl)(phenyl)methyl)piperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

40.0 g of 1-[(R)-(4-chlorophenyl) (phenyl) methyl] piperazine, 14.1 g of sodium hydrogen carbonateAnd a mixture of 78.1 g of N-methyl-2-pyrrolidoneHeat to 120 C, ethyl (2-chloroethoxy) acetateAfter 27.9 g was dropped over 30 minutes, the mixture was stirred for 6 hours.After cooling the obtained suspension to room temperature, 200 g of waterAnd toluene 69gAnd the mixture was separated.120 g of water is added to the obtained organic layer, and liquid separation is performed again to obtain the formula (6).; Example 1 32 g of water was added to a toluene solution of the compound (6) obtained in Reference Example 1, and a solution of 7.0 g of lithium hydroxide monohydrate dissolved in 44 g of water was added dropwise at room temperature. It stirred until it became 0.2% or less. Liquid separation was carried out after the obtained solution, 8 g of N-methyl-2-pyrrolidone for washing, 139 g of toluene and 25 g of acetone were mixed. To the separated aqueous layer were added 139 g of toluene and 13 g of acetone to carry out liquid separation again. Further, 139 g of toluene and 9 g of acetone were added to the separated aqueous layer, and liquid separation was performed again. 35 g of toluene and 193 g of methyl ethyl ketone were added to the obtained aqueous layer, and 29.1 g of 35% hydrochloric acid was dropped to adjust the pH to 2.4, and the solution was heated to 45 C. to separate. After 35 g of toluene was added to the obtained organic layer, concentration was performed until the remaining amount became 95 g. Furthermore, 97 g of methyl ethyl ketone and 35 g of toluene were added and concentrated until the remaining amount reached 99 g, and further 24 g of methyl ethyl ketone and 9 g of toluene were added and concentrated until the remaining amount became 101 g. After adding methyl ethyl ketone 64g and acetone 411g at room temperature and dropping 7.3g of 35% hydrochloric acid,0.04 g of levocetirizine dihydrochloride was added.Subsequently, 316 g of acetone was dropped, and after stirring for 1.5 hours, 6.9 g of 35% hydrochloric acid was dropped. After filtering the obtained suspension, the obtained solid was washed with 95 g of acetone. The obtained crystals were dried under reduced pressure at 40 C. to obtain 54.6 g of levocetirizine dihydrochloride. The purity was 99.8% or more, 300543-56-0

The synthetic route of 300543-56-0 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; Sumitomo Chemical Co., Ltd.; Yoshida, Kazuhiro; Ando, Kenichi; (13 pag.)JP2019/43885; (2019); A;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

5308-25-8, 1-Ethylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

According to scheme I, to a 250-mL flash were added Compound Ia-1, i.e. 2,6-dichloro-3,5-dimethoxyaniline (10mmol) and AcOH (24ml), and added dropwisely under an ice-bath a solution of sodium nitrite (15mmol) in sulphuric acid (5.8ml) . The mixture was stirred at 25C until the solution became clear. The resulting dark yellow solution was poured into 150ml of an ice-water, and urea (6mmol) was added. The mixture was stirred and filtered. An aqueous solution of potassium iodide (15mmol) was added to the above dark-yellow solution. The mixture was heated at 85C for 2 hours, and cooled to room temperature. NaHSO3 (3.4 mmol) was added, and the mixture was stirred for 10 minutes. The resulting yellow solid was filtered, dried, and separated by column chromatography to produce Compound Ib-1 (8mmol). Compound Ib-1 (4 mmol), and Compound A-1, i.e. 4-piperidinone ethylene ketal (6 mmol) were dissolved in 50ml toluene, and palladium acetate (0.4 mmol), BINAP (0.48 mmol), and cesium carbonate (18 mmol) were added. The mixture was refluxed under the nitrogen protection for 3 days, and separated by column chromatography to produce Compound Ic-1. Compound Ic-1 (2.5 mmol) was dissolved in 10ml THF, and 10% aqueous H2SO4 solution (10ml) was added. The mixture was heated at 60C overnight, and separated by column chromatography to produce Compound Id-1. Compound Id-1 (1.0 mmol) was dissolved in 10ml dioxane, and DMF.DMA (6.0 mmol) and triethylamine (1.0 mmol) were added. The mixture was refluxed under the nitrogen protection for 2 days, and separated by thin layer chromatography to produce Compound Ie-1. Compound B-1, i.e., 1-fluoro-4-nitrobenzene (10 mmol) was dissolved in 20ml DMF, and C-1, i.e., N-ethylpiperazine (11 mmol), and potassium carbonate (30 mmol) were added. The mixture was reacted at 70C overnight. After cooling, the mixture was poured into ice-water, and filtered to produce Compound If-1. Compound If-1 (10 mmol) was dissolved in 20ml methanol or ethanol, and palladium/carbon (1mmol) was added. The mixture was hydrogenated at room temperature for 7 hours. The mixture was separated by column chromatography to produce Compound Ig-1. Compound Ig-1 (2.6 mmol) was dissolved in 10ml dioxane, and cyanoamine (2.73 mmol), and concentrated hydrochloric acid (3.9 mmol) were added. The mixture was stirred under reflux overnight to produce Compound Ih-1. Compound Ie-1 (1mmol) and Compound Ih-1 (1.05mmol) were dissolved in 8ml ethanol, and sodium acetate (2mmol) and triethylamine (1.05mmol) were added. The mixture was stirred under flux for 7 hours, ethanol concentrated, and water and dichloromethane were added. The organic phase was separated, dried over anhydrous sodium sulphate, and separated by thin layer chromatography to produce Compound I-1 (0.1mmol) in a yield of 10%.H1-NMR(deuterated MeOH) : delta8.11(s, 1H), delta7.56(d, 2H), delta6.99(d, 2H), delta6.72(s, 1H), delta4.25(s, 2H), delta3.93(s, 6H), delta3.56(t, 2H), delta3.23(m, 4H), delta2.92(t, 2H), delta2.8(m, 4H), delta2.64(m, 3H), delta1.2(t, 3H). ESI(+)m/z: 543

5308-25-8, The synthetic route of 5308-25-8 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; Shanghai Allist Pharmaceutical and Medical Technology Corporations; KUANG, Rongren; (39 pag.)EP3466948; (2019); A1;,
Piperazine – Wikipedia
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

1-lsopropyl-4-(5-nitro-Pyridin-2-yl)-piperazine (NVP-BKT293)N-lsopropylpiperazine (1.8 mL, 12.7 mmol, 2 equiv) is added to a cold (5¡ãC) mixture of 2- chloro-5-nitropyridine (1 g, 6.3 mmol) in DCM (5 mL). The reaction mixture is allowed to warm to RT, stirred for 16h, diluted with DCM/H2O and extracted with DCM. The organic phase is washed with brine, dried (Na2SO4), filtered and concentrated to provide the title compound as a yellow solid: ES-MS: 251.2 [MH]+; tR= 2.20 min (system 1).

The synthetic route of 4318-42-7 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; NOVARTIS AG; NOVARTIS PHARMA GmbH; WO2007/71752; (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.122833-04-9,2-Methoxy-4-(4-methylpiperazin-1-yl)aniline,as a common compound, the synthetic route is as follows.

To a stirred solution of 2,5-dichloro-4-(3-fluoro-5-nitrophenoxy)-7-((2-(trimethylsilyl)ethoxy) methyl)-7H-pyrrolo[2,3-d]pyrimidine (2, 0.25 g, 0.5 mmol) in t-BuOH ( 10 mL), 2-methoxy-4-(4- methylpiperazin- l -yl)aniline (3, 0.1 16 g, 0.5 mmol), Pd2(dba)3 ( 13 mg, 0.01 mmol), X-PHOS (12 mg, 0.02 mmol), 2C03 (0.145 g, 1.0 mmol) were added and stirred at 90 C for 14 h. Reaction was monitored by TLC and LCMS. After completion of the reaction, reaction mixture was concentrated under reduced pressure, water was added, extracted with ethyl acetate. Organic layer was washed with brine, dried over anhydrous sodium sulfate and evaporated to dryness. Crude product was purified by column chromatography using 4% MeOH-DCM to afford 5-chloro-4-(3-fluoro-5-nitrophenoxy)-N-(2- methoxy-4-(4-methylpiperazin- l -yl)phenyl)-7-((2-(trimethylsilyl)ethoxy) methyl)-7H-pyrrolo[2,3- d]pyrimidin-2-amine (4, 0.233 g, 67%). NMR (400 MHz, CDC13): delta 8.10 (s, 1 H), 7.90-7.80 (d, 1 H), 7.42-7.40 (d, 1H), 7.30 (s, 1 H), 6.90 (s, 1H), 6.50 (s, 1 H), 6.40-6.30 (d, 1 H), 5.50 (s, 2H), 3.80 (s, 3H), 3.60-3.50 (t, 2H), 3.20-3.10 (m, 4H), 2.70-2.60 (m, 4H), 2.40 (s, 3H), 1.00-0.95 (t, 2H), 0.2 (s, 9H)., 122833-04-9

The synthetic route of 122833-04-9 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; GATEKEEPER PHARMACEUTICAL, INC.; GRAY, Nathanael, S.; ZHOU, Wenjun; WO2011/79231; (2011); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

31166-44-6, 1-Cbz-Piperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

In 2 mL of dimethyl acetamide were combined tert-butyl 4-chloro-5,8-dihydropyrido[3,4-d]pyrimidine-7(6H)-carboxylate (1.0 g, 3.7 mmol), triethylamine (1.0 mL, 7.4 mmol), and benzyl 1-piperazinecarboxylate (0.86 mL, 4.4 mmol). The reaction vessel was sealed and the reaction mixture was heated to 90¡ã C. with stirring. After 5 hours, the reaction was diluted with brine and extracted with methyl t-butyl ether. The combined organic layers were washed sequentially with saturated ammonium chloride and brine, dried over MgSO 4, and concentrated under reduced pressure to a thick oil. The oil was chromatographed (RediSep , 24 g) eluting with 1:1 ethyl acetate/Hexanes to give tert-butyl 4-(4-((benzyloxy)carbonyl)piperazin-1-yl)-5,8-dihydropyrido [3,4-d]pyrimidine-7(6H)-carboxylate (1.3 g, 2.9 mmol, 77% yield). ES+APCI MS m/z 454.2 [M+H] +., 31166-44-6

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

Reference£º
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

55112-42-0,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.55112-42-0,4-Methyl-1-piperazinecarbonyl Chloride Hydrochloride,as a common compound, the synthetic route is as follows.

Example 2: Preparation of Zopiclone in iso-Butyl acetate[0065] To a slurry of l-chlorocarbonyl-4-methyl piperazine hydrochloride(CMP) (52.96g) in iso-Butyl acetate (500 ml) were added Et3N (46.12g), DMAP (4.62g) and 7-OH-Py (5Og). The slurry was heated to 8O0C and the heating was maintained for about 5.5 h. After about 2h at 800C, 100 ml iso-Butyl acetate was added to the slurry. After the reaction completion (5.5 h, heating), the reaction was stopped and the slurry was cooled to the room temperature. Water (600ml) was added to the reaction mixture and the slurry was stirred at room temperature for 1 h. The formed solid was filtered, washed with water (50 ml) and acetone (25 ml) and dried in vacuum oven at 400C overnight to give zopiclone crude (74.97g .yield 91.7%, purity 98.86% by HPLC).

As the paragraph descriping shows that 55112-42-0 is playing an increasingly important role.

Reference£º
Patent; TEVA PHARMACEUTICAL INDUSTRIES LTD.; TEVA PHARMACEUTICALS USA, INC.; WO2008/2629; (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.129779-30-2,(3R,5S)-rel-tert-Butyl 3,5-dimethylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

[21851 Step 1: Synthesis of tert-butyl(3R.5S?)-4-(3-formylbenzyl)-3 .5-dimethylpiperazine- 1 -carboxylate[21861 (3R,55)-tert-butyl 3 ,5-dimethylpiperazine- 1 -carboxylate (formula 8-1, 2.730 g, 12.739 mmol), 3-(bromomethyl)benzaldehyde (2.789 g, 14.013 mmol) and Cs2CO3 (8.301 g, 25.478 mmol) were mixed in acetonitrile (50 mL) at room temperature, and the mixture was stirred at the same temperature for 18 hours. The reaction mixture was filtered through a paper filter to remove solids, and the filtrate was purified by column chromatography (silicon dioxide, 120 g cartridge; ethyl acetate/hexane = from 5 % to 30 %) and concentrated to afford the desired compound (2.730 g, 64.5 %) as a yellow oil.

129779-30-2, The synthetic route of 129779-30-2 has been constantly updated, and we look forward to future research findings.

Reference£º
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