Heterocyclic Building Blocks-piperazine

21043-40-3, 1-Cyclopentylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,21043-40-3

(General Procedure 16)4-Cyclopentyl-piperazine-1-carboxylic Acid 4-iodo-pyrazol-1-yl Ester The title compound was prepared from 1-hydroxy-4-iodopyrazole and N-cyclopentylpiperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane-3% Et3N) (61%, crystals). 1H NMR (300 MHz; CDCl3): delta 1.33-1.94 (m, 8H), 2.46-2.61 (m, 5H), 3.57 (bt, 2H), 3.67 (bt, 2H), 3.63 (bs, 2H), 3.77 (bs, 2H), 7.40 (d, 1H), 7.44 (d, 1H); HPLC-MS: m/z=391.1 (M+1); Rt=1.31 min.

21043-40-3 1-Cyclopentylpiperazine 806421, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; Ebdrup, Soren; de Jong, Johannes Cornelis; Jacobsen, Poul; Hansen, Holger Claus; Vedso, Per; US2003/166644; (2003); A1;,
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109-01-3, 1-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

350 ml of ethanol was added to 155 g (1.547 mol) of N-methylpiperazine. At room temperature (25+/-3 C.), 60 g (0.351 mol) of 4-chloromethylbenzoic acid was added thereto and stirred for 6-7 hours. The reaction was analyzed by HPLC, and then the reaction solution was distilled under reduced pressure to remove ethanol, and 60 ml of 1-butanol was added thereto. The mixture was azeotropically distilled at 70+/-2 C. and concentrated to produce a solid. 600 ml of 2-propanol was added thereto and the mixture was stirred at room temperature (25+/-3 C.) for 30 minutes, stirred under reflux for 15 minutes, and then stirred at room temperature (25+/-3 C.) for 12 hours with slow cooling. The produced precipitate was cooled to 19+/-3 C., stirred for 1 hour and then filtered. The filtrate was washed with 50 ml of cooled 2-propanol and dried in an oven at 60 C., thereby obtaining a white compound of formula (2) (60 g, yield: 72%, purity: 95% or higher).HPLC purity: 99.123% (desmethyl impurity: 0.042%, starting material 0.42%).Thin layer chromatography: Methanol-Dichloromethane (7:5), Rf: 0.2., 109-01-3

109-01-3 1-Methylpiperazine 53167, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; BCWORLD PHARM. CO., LTD.; US2012/330014; (2012); A1;,
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With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.163765-44-4,(R)-1-Boc-3-Methylpiperazine,as a common compound, the synthetic route is as follows.

Intermediate 8 tert-Butyl (3R)-4-(chlorocarbonyl)-3 -methylpiperazine- 1 -carboxylateTo a mixture of triphosgene (23 g, 75 mmol) in anhydrous DCM (250 mL) was added pyridine (18 g, 225 mmol) drop-wise followed by addition of tert-butyl (3R)-3- methylpiperazine-1 -carboxylate (15 g, 75 mmol) at 0 C. The mixture was stirred overnight at RT. TLC showed the starting material had been consumed. The mixture was concentrated to afford Intermediate 8 as yellow solid, which was used without further purification., 163765-44-4

As the paragraph descriping shows that 163765-44-4 is playing an increasingly important role.

Reference：
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; LI, David, Yunzhi; WANG, Jiabing; YANG, Zhenfan; ZENG, Qingbei; ZHANG, Xiaolin; WO2014/135876; (2014); A1;,
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25057-77-6, 1,2-Dimethylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Reference Example 7 To a solution of N-benzyl-4-piperidone (8.0 g) and 3,4-dimethylpiperazine (9.5 g) in ethanol (100 ml) are added 5% platinum-carbon (2 g) and acetic acid (14.4 ml), and the mixture is subjected to catalytic hydrogenation at room temperature under atmospheric pressure. The catalyst is removed by filtration, and the filtrate is concentrated under reduced pressure. Water is added to the resultant, and the mixture is basified with a 5% aqueous sodium hydroxide solution, and the mixture is extracted with diethyl ether. The extract is washed with water, dried and concentrated under reduced pressure to remove the solvent. The residue is dissolved in ethanol, and thereto is added to conc. hydrochloric acid to give a hydrochloride. The resulting white powder is collected by filtration, dissolved in water, and basified with a 5% aqueous sodium hydroxide solution. The mixture is extracted with diethyl ether, washed with water, dried, and concentrated under reduced pressure to give 4-(3,4-dimethyl-1-piperazinyl)-1-benzylpiperidine (4.2 g). 1 H-NMR (CDCl3) deltappm: 1.04 (3H, d, J=6 Hz), 1.45-2.5 (12H, m), 2.27 (3H, s), 2.7-3.05 (4H, m), 3.48 (2H, s), 7.31 (5H, m).

25057-77-6, The synthetic route of 25057-77-6 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Otsuka Pharmaceutical Company, Limited; US6140330; (2000); A;,
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With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.259808-67-8,1-Boc-3,3-Dimethylpiperazine,as a common compound, the synthetic route is as follows.

To a solution of tert-butyl 3,3-dimethylpiperazine-l-carboxylate (500 mg, 2.333 mmol) in DCM (11 ml) at 0 C was added TEA (0.976 ml, 7.00 mmol) and methanesulfonyl chloride (321 mg, 2.80 mmol) and the resulting mixture was stirred RT for 3 h. The volatiles were removed under reduced pressure. The residue was purified via silica gel chromatography (5 – 100 % EtOAc in hexanes) to give tert-butyl 3,3-dimethyl-4-(methylsulfonyl)piperazine-l-carboxylate (600 mg, 2.052 mmol, 88 % yield) as a colorless liquid. MS (ES+) C^H^C^S requires: 292, found: 293 [M+H] +., 259808-67-8

The synthetic route of 259808-67-8 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; TESARO, INC.; LEWIS, Richard T.; JONES, Philip; PETROCCHI, Alessia; REYNA, Naphtali; HAMILTON, Matthew; CROSS, Jason; TREMBLAY, Martin; LEONARD, Paul Graham; (216 pag.)WO2018/136887; (2018); A1;,
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123987-13-3, (3-(4-Methylpiperazin-1-yl)phenyl)methanol is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

A mixture of 18 (5.00 g, 19.1 mmol), /V-methylpiperazine (5.73 g, 57.2 mmol), Pd2(dba)3(3.49 g, 3.82 mmol), Cs2C03(12.4 g, 38.2 mmol) and 2,2′-bis(diphenylphosphino)-1 ,1 ‘-binaphthalene (3.56 g, 5.72 mmol) in 1 ,4-dioxane (5 mL) was degassed and purged with N2for 3 times, and then the mixture was stirred at 80 C for 18 h under N2atmosphere. Then the mixture was cooled to 15 C, filtered and concentrated in vacuum. The residue was purified via column chromatography (DCM/MeOH = 20:1) to give 19 (1.40 g, 31 %) as brown oil.1H NMR (400 MHz, DMSO-d6) 7.60 (s, 1 H), 7.52 (d, J = 7.5 Hz, 1 H), 7.34 – 7.30 (m, 1 H), 7.12 (dd, J = 7.7, 2.4 Hz, 1 H), 3.91 (s, 3H), 3.29 – 3.25 (m, 4H), 2.62 – 2.65 (m, 4H), 2.37 (s, 3H). To a solution of 19 (1.40 g, 5.98 mmol) in THF (10 mL) was added LiAIH4(454 mg, 12.0 mmol) at 0 C. The mixture was stirred at 70 C for 2 h. The mixture was cooled to 0 C and quenched by saturated solution of potassium sodium tartrate (3 mL), the precipitate formed was collected, filtered to remove the precipitate. The organic phase was concentrated in vacuum. The residue was purified via column chromatography (DCM/MeOH = 20:1) to give 20 (530 mg, 43%) as brown solid.1H NMR (400 MHz, DMSO-de) 7.26 (s, 1 H), 6.96 (s, 1 H), 6.91 – 6.80 (m, 2H), 4.66 (s, 2H), 3.32 – 3.05 (m, 4H), 2.66 – 2.48 (m, 4H), 2.36 (s, 3H). To a solution of 20 (530 mg, 2.57 mmol) in DCM (10 mL) was added /V-Boc- (S)-valine (670 mg, 3.08 mmol), DCC (795 mg, 3.86 mmol) and DMAP (62.8 mg, 0.514 mmol). The mixture was stirred at 15 C for 24 h. The mixture was filtered and concentrated in vacuum. The residue was purified by column chromatography (DC / eOH = 20:1) to give 21 (600 mg, 58%) as a brown solid. To a solution of 21 (200 mg, 0.493 mmol) in EtOAc (5 mL) was added HCI/EtOAc (4 , 2 mL). The mixture was stirred at 15 C for 15 h. Then the mixture was concentrated in vacuum, the precipitate formed was collected by filtration to give 22 (120 mg, 71 %) as a yellow solid.

123987-13-3, The synthetic route of 123987-13-3 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; ANACOR PHARMACEUTICALS, INC.; AKAMA, Tsutomu; CARTER, David Scott; HALLADAY, Jason S.; JACOBS, Robert T.; LIU, Yang; PLATTNER, Jacob J.; ZHANG, Yong-Kang; WITTY, Michael John; (149 pag.)WO2017/195069; (2017); A1;,
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With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.75336-86-6,(R)-2-Methylpiperazine,as a common compound, the synthetic route is as follows.,75336-86-6

i) tert-Butyl (3/?)-3-methylpiperazine-l-carboxylate;To a solution of (2No.)-2-methylpiperazine (Ig) in THF (10ml) was added di-tert-butyldicarbonate (1.45g). The reaction mixture was allowed to stir at room temperaturefor 18h.The reaction mixture was then partitioned between DCM (100 ml) and HaO (100 ml). Theorganics were separated and the aqueous layer was re-extracted with DCM (2 x 150ml).Organics were combined, dried (MgSO4) and reduced in vacuo to give the subtitle compoundas a clear oil. Yield: 1. Ig’H NMR: (DMSO) 8 0.92 (d, 3H), 1.38 (s, 9H), 2.57-2.70 (m, 1H), 2.76-2.81 (m, 1H), 2.87-2.99 (m, 1H), 3.66-3.74 (m, 4H)

The synthetic route of 75336-86-6 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2006/24823; (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.57260-71-6,tert-Butyl piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

57260-71-6, b) 4-(5-Trifluoromethyl-thiazol-2-yl)-piperazine-l-carboxylic acid tert-butyl esterTo a solution of 17.5 mmol 2-benzenesulfonyl-3-trifluoromethyl-oxirane in 20 ml N,N-dimethylformamide was added 15.9 mmol 4-thiocarbamoyl-piperazine-l-carboxylic acid tert-butyl ester (prepared from tert-butyl 1-piperazinecarboxylate, 1,1′- thiocarbonyldiimidazole and ammonia according to the procedure of J. Med. Chem. 1998, 41, 5037-5054). The mixture was heated at 90 0C for 10 h. The reaction mixture was then concentrated in vacuo and the residue purified by chromatography (SiO2, ethyl acetate/heptane) to afford the title compound as an orange crystalline solid (yield 26%). MS (m/e): 338.1 (M+H+, 100%).; a) 4-(5-Hydroxymethyl-thiazol-2-yl)-piperazine-l-carboxylic acid tert-butyl esterTo a solution of 179 mmol 30% aqueous hydrogen peroxide in 60 ml water was added 1 N aqueous sodium hydroxide solution until the pH was 9. The reaction mixture was then cooled to 100C and 163 mmol acrolein was added dropwise. Further amounts of 1 N aqueous sodium hydroxide solution were added during the addition in order to maintain the pH of the reaction mixture between pH 8 and 9. The mixture was stirred for 30 min at 0 0C and then 40.8 mmol thiocarbamoyl-piperazine-1-carboxylic acid tert- butyl ester (prepared from tert-butyl 1-piperazinecarboxylate, 1,1′- thiocarbonyldiimidazole and ammonia according to the procedure of J. Med. Chem. 1998, 41, 5037-5054) was added. To the resulting suspension was added 25 ml ethanol and the mixture was heated at 80 0C for 30 min. The resulting solution was diluted with ethyl acetate/tetrahydrofuran (1:1) and the mixture was washed twice with brine. The organic phase was dried over sodium sulphate and concentrated in vacuo to afford the title compound as a yellow oil (yield 99%). MS (m/e): 300.3 (M+H+, 100%).;f) 4-(4-Methyl-5-trifluoromethyl-thiazol-2-yl)-piperazine-l-carboxylic acid tert-butyl esterA mixture of 4.92 mmol rac-2-benzenesulfonyl-2-methyl-3-trifluoromethyl- oxirane and 5.41 mmol 4-thiocarbamoyl-piperazine-l-carboxylic acid tert-butyl ester (prepared from tert-butyl 1-piperazinecarboxylate, l.l’-thiocarbonyldiimidazole and ammonia according to the procedure of J. Med. Chem. 1998, 41, 5037-5054) in 15 ml N,N-dimethylformamide was heated at 100 0C for 4.5 h. The reaction mixture was then concentrated in vacuo and the residue purified by chromatography (SiO2, ethyl acetate/heptane) to afford the title compound as a yellow crystalline solid (yield 30%). MS (m/e): 352.3 (M+H+, 100%).; a) 4-(Dimethylaminomethylene-thiocarbamoyl)-piperazine-l-carboxylic acid tert-butyl esterA mixture of 122 mmol N,N-dirnethylformamide dimethyl acetal and 6.11 mmol 4- thiocarbamoyl-piperazine-1-carboxylic acid tert-butyl ester (prepared from tert-butyl 1- piperazinecarboxylate, lj’-thiocarbonyldiimidazole and ammonia according to the procedure of J. Med. Chem. 1998, 41, 5037-5054) was heated at 110 0C for 3 h. The reaction mixture was then concentrated in vacuo and the residue was resuspended in ethyl acetate/ tetrahydrofuran ( 1:1) and washed with brine. The organic phase was dried over sodium sulphate and concentrated in vacuo to afford the title compound as a light yellow crystalline solid (yield 95%). MS (m/e): 301.4 (M+H+, 100%).

57260-71-6 tert-Butyl piperazine-1-carboxylate 143452, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; F. HOFFMANN-LA ROCHE AG; WO2006/72436; (2006); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

59702-07-7,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.59702-07-7,1-Methylpiperazin-2-one,as a common compound, the synthetic route is as follows.

An oven-dried microwave vial (0.5-2.0 ml_ volume) was charged with (S)-2- cyclopropyl-10-((2,5-dichloropyrimidin-4-yl)amino)-3,3-difluoro-7-methyl-1 ,2,3,4-tetrahydro- [1 ,4]oxazepino[2,3-c]quinolin-6(7/-/)-one (Intermediate A10a; 7 mg, 0.015 mmol), 1- methylpiperazin-2-one (4 mg, 0.037 mmol) and DIPEA (13 uL, 0.075 mmol). The reaction vial was flushed with Ar and sealed with a cap. NMP (0.65 ml_) was added and the reaction mixture was heated at 140C under microwave irradiation for 1 h. The reaction mixture was dissolved in DMSO (0.8 ml_) and directly purified by reverse-phase chromatography (Biotage reverse-phase 12 g Ultra C-18 column; 10-60-80-100% MeOH in H2O (containing 0.1 % formic acid)). The product-containing fractions were combined, passed through an SCX-2 (1 g), additional MeOH (10 ml_) was passed through and the product was eluted with 2 N methanolic ammonia (25 ml_). The solvent was removed in vacuo affording the title compound (5 mg, 57%) as an off-white solid. 1 H NMR (600 MHz, methanol-d?) d 8.04 (d, J = 2.2 Hz, 1 H), 8.01 (s, 1 H), 7.92 (dd, J = 9.1 , 2.2 Hz, 1 H), 7.57 (d, J = 9.1 Hz, 1 H), 4.53- 4.38 (m, 2 H), 4.24 (d, J = 18.2 Hz, 1 H), 4.18 (d, J = 18.2 Hz, 1 H), 3.98-3.92 (m, 1 H), 3.92-3.87 (m, 1 H), 3.73 (s, 3 H), 3.47-3.39 (m, 2 H), 3.35-3.28 (m, 1 H), 2.98 (s, 3 H), 1.42-1.37 (m, 1 H), 0.82-0.75 (m, 1 H) 0.68-0.57 (m, 2 H), 0.37-0.31 (m, 1 H); LCMS (Method X4) RT 2.85 min; m/z calcd for C25H27CIF2N703+ [M+H]+: 546.1832, Found: 546.18342.

59702-07-7 1-Methylpiperazin-2-one 4399042, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; CANCER RESEARCH TECHNOLOGY LIMITED; THE INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL; BELLENIE, Benjamin Richard; CHEUNG, Kwai Ming Jack; DAVIS, Owen Alexander; HOELDER, Swen; HUCKVALE, Rosemary; COLLIE, Gavin; MENICONI, Mirco; BRENNAN, Alfie; LLOYD, Matthew Garth; (222 pag.)WO2019/197842; (2019); A1;,
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70261-82-4, 4-(4-Methylpiperazin-1-ylmethyl)phenylamine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Example 249; 2 ‘-Chloro-5 ‘-(cyclohexanecarbonyl-amino)-biphenyl-4-carboxylic acid [4-(4-methyl- piperazin- 1 -ylmethyl)-phenyl] -amide; A mixture of 2′-Chloro-5’-(cyclohexanecarbonyl-amino)-biphenyl-4-carboxylic acid(103mg), 4-(4-methyl-pirhoerazin-l-ylmethyl)-phenylamine (59mg) and HBTU (148mg) in dry DMF (1 OmI) containing triethylamine (362mul) was stirred at room temp for 18h.Most of the DMF was evaporated and the residue diluted with water. The resulting solid was collected by filtration. This material was then purified by reverse phase Prep HPLC giving the title compound as a yellow solid (51mg) EPO 1H NMR (DMSO, delta) 1.10-1.81 (1OH, m), 2.17 (3H, s), 2.24-2.28 (9H, m), 3.43 (2H, s),7.29 (2H, d), 7.41-7.61 (2H, m), 7.67 (IH, dd), 7.71-7.81 (2H, m), 8.05 (2H5 d,), 8.83(2H, m), 10.13 (IH, s), 10.36 (IH, s).LCMS- ES+ = 544,546., 70261-82-4

70261-82-4 4-(4-Methylpiperazin-1-ylmethyl)phenylamine 3153996, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; ARROW THERAPEUTICS LIMITED; WO2007/31791; (2007); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics