Heterocyclic Building Blocks-piperazine

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.20327-23-5,1-Cyclopropylpiperazine,as a common compound, the synthetic route is as follows.

The title compound (pale beige solid, 26.5 mg, 40%) was prepared by a procedure similar to Example 400 using (S)-2-methyl-4-(5-(4,4,5,5-tetramethyl- l,3,2-dioxaborolan-2-yl)pyridin-2-yl)mo holine (50 mg, 80% purity, 0.16 mmol) and N-(5-bromo-4-fluoro-2-((3S,5R)-3,4,5-trimethylpiperazin-l-yl)phenyl)-6-oxo-4- (trifluoromethyl)-l,6-dihydropyridine-3-carboxamide (50.5 mg, 0.1 mmol). 1H NMR (500MHz, METHANOL-d4) delta = 8.32 (s, 1H), 7.97 (s, 1H), 7.92 (br d, J=8.4 Hz, 1H), 7.79 (br d, J=8.8 Hz, 1H), 7.07 (d, J=12.1 Hz, 1H), 6.95 – 6.90 (m, 2H), 4.16 (br d, J=12.7 Hz, 1H), 4.10 – 3.99 (m, 2H), 3.75 – 3.66 (m, 2H), 3.07 (br d, J=10.5 Hz, 2H), 2.96 (dt, J=3.4, 12.3 Hz, 1H), 2.70 – 2.56 (m, 5H), 2.41 (s, 3H), 1.26 (d, J=6.2 Hz, 3H), 1.19 (d, J=5.7 Hz, 6H); LCMS [M + H]+ 603.6.

20327-23-5, As the paragraph descriping shows that 20327-23-5 is playing an increasingly important role.

Reference：
Patent; ONTARIO INSTITUTE FOR CANCER RESEARCH (OICR); AL-AWAR, Rima; ZEPEDA-VELAZQUEZ, Carlos Armando; PODA, Gennady; ISAAC, Methvin; UEHLING, David; WILSON, Brian; JOSEPH, Babu; LIU, Yong; SUBRAMANIAN, Pandiaraju; MAMAI, Ahmed; PRAKESCH, Michael; STILLE, Julia Kathleen; (1053 pag.)WO2017/147700; (2017); A1;,
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314741-39-4, (S)-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 solution of Example 1(c) in dry tetrahydrofuran (40ml) at 0C was treated with lithium aluminium hydride (0.50g) and the mixture was stirred at 0C for 1.5 hours.. The cooled solution was treated dropwise with a solution of 2M sodium hydroxide until a white precipitate had formed.. Dichloromethane and anhydrous sodium sulfate were added and the solution was filtered and evaporated to give a pale yellow oil (3.0g). MS (+ve ion electrospray) m/z 217 (MH+).

314741-39-4, 314741-39-4 (S)-1-tert-Butyl 3-methyl piperazine-1,3-dicarboxylate 1501855, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; SmithKline Beecham plc; EP1187828; (2004); B1;,
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Piperazines – an overview | ScienceDirect Topics

21655-48-1, cis-2,6-Dimethylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

General procedure: Methyl 4-fluorobenzoate (4.6 g, 29.7 mmol) was dissolved in DMSO (20 mL), followed by the addition of K2CO3 (12.3 g, 89.1 mmol) and 1-ethylpiperazine (7.6 mL, 59.4 mmol). The mixture was heated to 110 °C and stirred for 10 h before being cooled to room temperature and diluted with water (50 mL) and EtOAc (200 mL). The organic phase was washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated. The residue was purified by silica gel column chromatography using CH2Cl2?MeOH (10:1) to get 4a (6.4 g, 89.2percent) as a yellow solid.

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

Reference：
Article; Cui, Jing; Peng, Xia; Gao, Dingding; Dai, Yang; Ai, Jing; Li, Yingxia; Bioorganic and Medicinal Chemistry Letters; vol. 27; 16; (2017); p. 3782 – 3786;,
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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 Intermediate E (59 mg, 0.20 mmol) in DMF (3 mL) were added tert-butyl 3,3-dimethylpiperazine-1-carboxylate (50.7 mg, 0.24 mmol), HATU (97.4 mg, 0.26 mmol) and DIPEA (51 mg, 69 .iL, 0.39 mmol) and the resulting mixture was stirred at rt ON. The reaction mixture was then diluted with EtOAc, washed with water and brine consecutively, dried over anhydrous sodium sulfate, filtered and concentrated to dryness. The residue was purified by flash chromatography eluting with EtOAc/Hexanes 0-50% in 20 CV to obtain tert-butyl 4- [6-(4-fluorophenyl)-8-isopropyl-imidazo[ 1 ,2-b]pyridazine-2-carbonyl] – 3,3-dimethyl-piperazine-1-carboxylate (58 mg) as a white solid. ?H NMR (400 MHz, CDC13) oe 8.33 (s, 1H), 8.11 -7.87 (m, 2H), 7.24-7.10 (m, 3H), 4.28 (s, 2H), 3.77 -3.43 (m, 5H), 1.61 (s, 6H), 1.51 – 1.40 (m, 15H). LC-MS: 497.5 (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; VERTEX PHARMACEUTICALS INCORPORATED; FARMER, Luc J.; FOURNIER, Pierre-Andre; LESSARD, Stephanie; LIU, Bingcan; ST-ONGE, Miguel; STURINO, Claudio; SZYCHOWSKI, Janek; YANNOPOULOS, Constantin; WO2015/48245; (2015); A1;,
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301673-16-5, tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Sodium hydroxide (IN aqueous solution, 20 mL, 20 mmol) was added to a solution of Intermediate B (2.59 g, 10.7 mmol) in EtOH (20 mL), and the reaction mixture was heated to 70 0C for 1 h. Upon cooling to rt, the EtOH was removed under reduced pressure. The aqueous solution was diluted with THF (40 mL) and benzyl chloroformate (1.60 mL, 10.7 mmol) was added. After 1 h, the reaction mixture was diluted with water (50 mL) and was extracted with EtOAc (3 x 50 mL). The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The material was purified by column chomatography (20 to 40percent EtOAc in Hexane gradient) to give 3.16 g (85percent) of the desired product as a thick oil. LC-MS: RT = 8.41 min., [M+H]+ = 373.1.

301673-16-5, As the paragraph descriping shows that 301673-16-5 is playing an increasingly important role.

Reference：
Patent; CRITICAL THERAPEUTICS, INC.; WO2007/146066; (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.120737-59-9,tert-Butyl 3-methylpiperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

1-(tert-Butoxycarbonyl)-3-methylpiperazine (Oakwood Co., 1.36 g), 5-bromo-2-chlorobenzotrifluoride (Tokyo Chemical Industry CO., LTD., 2.0 g), 2-(di-tert-phosphino)biphenyl (STREM, 41 mg), tris(dibenzylideneacetone)dipalladium (Aldrich Co., 62 mg) and sodium tert-butoxide (980 mg) were added to toluene (10 ml), and the mixture was stirred with heating at 60°C for 3 hr. After completion of the reaction, the insoluble material was filtered off, and the filtrate was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (elution solvent: hexane-ethyl acetate (7:1-3:1)). A 4N hydrochloric acid-ethyl acetate solution was added to the obtained solid and the mixture was stirred for 5 hr. Diethyl ether was added thereto, and the precipitated solid was collected by filtration to give 1-[4-chloro-3-(trifluoromethyl)phenyl]-2-methylpiperazine hydrochloride (692 mg, yield 32percent). 1H-NMR(400MHz,DMSO-d6)delta(ppm): 1.11-1.23 (3H,m), 3.01-3.30(5H,m), 4.27-4.31(1H,m), 7.21-7.55(3H,m), 9.10(1H,s), 9.61(1H,s)., 120737-59-9

Big data shows that 120737-59-9 is playing an increasingly important role.

Reference：
Patent; Mitsubishi Pharma Corporation; EP1714961; (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.630125-91-6,4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline,as a common compound, the synthetic route is as follows.

To a stirred solution of 4-((4-ethylpiperazin- 1 -yl)methyl)-3-(trifluoromethyl)aniline (Intermediate Cl) (150 mg, 0.52 mmol) in THF (20 mL) was added triphosgene (54 mg, 0.18 mmol) and the resulting mixture was stirred at 70 C. After 1 h of heating the mixture wasconcentrated under reduced pressure and the residue was dissolved in THF (20 mL). That solution was added dropwise to a stirred mixture of tert-butyl 4-(5-amino-2-chlorophenoxy)- 6H-pyrimido [5,4-b] [1 ,4]oxazine-8(7H-carboxylate (step 1 intermediate) (150 mg, 0.40 mmol) and triethylamine (172 jiL, 1.19 mmol) in THF (20 mL) at RT. The resultant mixture was stirred for 2 h at 70 C. The mixture was cooled to RT and quenched with water. Theaqueous mixture was extracted twice with ethyl acetate. The combined organic layers were washed with water followed by brine. The solution was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue thus obtained was purified by silica gel column chromatography to yield 100 mg of the desired product. ?H NMR (400 MHz, DMSO-d6) oe 1.09 (t, J= 7.2 Hz, 3H), 1.50 (s, 9H), 2.42-2.5 1 (m, 1OH), 3.54 (br s, 2H),3.94 (t, J= 8.4 Hz, 2H), 4.40 (t, J= 7.6 Hz, 2H), 7.29 (dd, J, = 2.4 Hz, J2 = 8.0 Hz, 1H), 7.48(d, J 8.8 Hz, 1H), 7.55-7.94 (m, 3H), 7.95 (s, 1H), 8.05 (s, 1H), 9.15 (s, 1H), 9.20 (s, 1H)., 630125-91-6

The synthetic route of 630125-91-6 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; GLENMARK PHARMACEUTICALS S.A.; PATEL, Vinod; REDDY, Venkateshwar; GHARAT, Laxmikant Atmaram; CHAUDHARI, Sachin Sundarlal; DAS, Sanjib; VELGALETI, Ranganadh; SHAH, Daisy Manish; BAJPAI, Malini; (262 pag.)WO2018/215668; (2018); A1;,
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Piperazines – an overview | ScienceDirect Topics

109-07-9, 2-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Example 1 In a 100 ml four-neck flask, 5.00 g (= 0.0499 mole) of racemic 2-methylpiperazine was placed, and 44 g of 1-butanol (water content 0.05 wt%) was added for dissolution. The solution was cooled to 0C, and 8.47 g of benzyl chlorocarbonate (= 0.0489 mole, purity by HPLC determination analysis 98.5 wt%, 0.98 molar time) was added dropwise in a liquid temperature range from 0 to 8C. Then, stirring was carried out at 0 to 5C for 2 hours, and the reaction solution was partially sampled and determined by the internal standard method (internal standard: anisole). As a result, the reaction yield of 1-benzyloxycarbonyl-3-methylpiperazine was 83.9% (based on the amount of 2-methylpiperazine). The reaction solution was further stirred at room temperature for 12 hours and analyzed. As a result, the reaction yield was 85.1%. Example 3 A reaction was performed as described for Example 1, except that the amount of benzyl chlorocarbonate used was changed from 8.47 g to 10.1 g (= 0.0597 mole, 1.17 molar times). As a result, the reaction yield of 1-benzyloxycarbonyl-3-methylpiperazine was 93.8% (based on the amount of 2-methylpiperazine) after lapse of 2 hours at 0 to 5C. Stirring was carried out at room temperature for further 12 hours, being followed by analysis. As a result, the reaction yield was 95.1%., 109-07-9

As the paragraph descriping shows that 109-07-9 is playing an increasingly important role.

Reference：
Patent; Toray Fine Chemicals Co., Ltd.; EP1548010; (2005); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

50606-32-1,50606-32-1, Butyl piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

50.3. 4-[(R)-2-tert-Butoxycarbonylamino-3-(diethoxy-phosphoryl)-propionyl]-piperazine-l- carboxylic acid butyl ester: To a solution of intermediate 50.2 (7.37 g) in DCM (95 mL), THF (24 mL) and DIPEA (16.3 mL) were added HOBT (3.83 g) and EDC-HCl (4.78 g), and the reaction mixture was stirred at RT for 10 min. Subsequently, piperazine- 1 -carboxylic acid butyl ester (5.31 g) was added and the mixture stirred at RT for 2.5 h. The reaction mixture was diluted with DCM, the org. phase washed with sat. aq. NaHCO3 and the aq. phase re-extracted with DCM. The combined org. phases were washed with brine, dried over Na2SO^ and concentrated to dryness. Purification by CC (EtOAc/MeOH 1:0 to 9: 1) gave 7.66 g of the desired product. LC-MS: tR = 0.94 min; [M+H]+: 494.00

50606-32-1 Butyl piperazine-1-carboxylate 21963126, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; ACTELION PHARMACEUTICALS LTD; CAROFF, Eva; HILPERT, Kurt; HUBLER, Francis; MEYER, Emmanuel; RENNEBERG, Dorte; WO2010/116328; (2010); A2;,
Piperazine – Wikipedia
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With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.54699-92-2,4-Methyl-1-piperazineacetic acid,as a common compound, the synthetic route is as follows.,54699-92-2

Example 11; Synthesis of Active Esters Of N-Methyl Piperazine Acetic Acid Via Oxalyl Chloride (Scheme B, FIG. 4B); To a suspension of N-methyl piperazine acetic acid (N-MPAA) (79 mg, 0.5 mmol) in DCM (25 mL) was added a solution of oxalyl chloride (4 mL, 0.8 mmol, 2.0 M solution in DCM) over 10 minute at room temperature. After another 30 minutes of reaction, solvent and excess reagent were removed under reduced pressure to give a white solid (23). A solution of NHS (57 mg, 0.5 mmol) in DCM (25 mL) was added to the solid followed by ss-TBD (390 mg, 1 mmol, 2.6 mmol/g). The resulting solution was sonicated for 5 minute when all solid dissolved. The ss-TBD resin was removed by filtration and solvent was evaporated to yield a white foam (97% yield). Product was characterized by ES-MS as before.

The synthetic route of 54699-92-2 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Applera Corporation.; US2005/148773; (2005); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics