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1235865-77-6 2-((1H-Pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid 66713100, apiperazines compound, is more and more widely used in various fields.

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.1235865-77-6,2-((1H-Pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid,as a common compound, the synthetic route is as follows.

(0413) To a solution of Compound 3J (90 mg), Compound 130C (64.2 mg), triethylamine (0.077 ml), N,N-dimethylpyridin-4-amine (38.5 mg) in a mixture of dichloromethane (5 ml) and N,N-dimethylformamide (0.5 ml) was added N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine, hydrochloric acid (60.4 mg) and the mixture was stirred 18 hours. This was concentrated on high vacuum and the crude was purified by reverse phase chromatography with ammonium acetate buffer/acetonitrile. 1H NMR (500 MHz, pyridine-d5) delta 13.03 (s, 1H), 9.27 (d, 1H), 8.59 (d, 1H), 8.43 (d, 1H), 8.37 (dd, 1H), 8.11 (d, 1H), 7.65-7.67 (m, 2H), 7.44 (d, 2H), 7.07 (d, 2H), 6.88 (d, 1H), 6.76 (dd, 1H), 6.54 (d, 1H), 6.48 (m, 1H), 4.06 (m, 1H), 3.98 (d, 2H), 3.35 (t, 2H), 3.07 (m, 4H), 2.73-2.80 (m, 4H), 2.68-2.72 (m, 1H), 2.36 (q, 1H), 2.11-2.30 (m, 9H), 1.97 (m, 2H), 1.62-1.71 (m, 3H), 1.48-1.58 (m, 2H), 1.39 (t, 2H), 0.94 (s, 6H)., 1235865-77-6

Reference：
Patent; AbbVie Inc.; Catron, Nathaniel; Lindley, David; Miller, Jonathan M.; Schmitt, Eric A.; Tong, Ping; US10213433; (2019); B2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

New learning discoveries about 2-((1H-Pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid

1235865-77-6, As the paragraph descriping shows that 1235865-77-6 is playing an increasingly important role.

(0122) To a mixture of Compound 3J (59.8 mg, 0.105 mmol), Compound 11B (33 mg, 0.105 mmol) and N,N-dimethylpyridin-4-amine (38.4 mg, 0.314 mmol) in dichloromethane (5 ml) was added 1-ethyl-3-[3-(dimethylamino)propyl]-carbodiimide hydrochloride (24.07 mg, 0.13 mmol). The reaction mixture was stirred at room temperature overnight and concentrated. The residue was purified by reverse phase HPLC on a C18 column using a gradient of 40-60% acetonitrile/0.1% trifluoroacetic acid in water to give the title compound as the trifluoroacetate salt. The trifluoroacetic acid salt was dissolved in dichloromethane (6 ml) and washed with 50% aqueous NaHCO3. The organic layer was dried over anhydrous Na2SO4 and concentrated to give the title compound. 1H NMR (500 MHz, dimethylsulfoxide-d6) delta 11.68 (s, 1 H), 11.40 (s, br, 1 H), 8.53-8.58 (m, 2 H), 8.04 (d, 1 H), 7.80 (dd, 1 H), 7.47-7.54 (m, 3 H), 7.34 (d, 2 H), 7.02-7.09 (m, 3 H), 6.67 (dd, 1 H), 6.39 (dd, 1 H), 6.19 (d, 1 H), 3.79 (dd, 1 H), 3.69-3.73 (m, 1 H), 3.22-3.37 (m, 3 H), 3.16-3.21 (m, 1 H), 3.07 (s, 4 H), 2.74 (s, 2 H), 2.09-2.24 (m, 6 H), 1.95 (s, 2 H), 1.86-1.93 (m, 1 H), 1.79-1.85 (m, 1 H), 1.58-1.64 (m, 1 H), 1.42-1.51 (m, 1 H), 1.38 (t, 2 H), 1.25-1.34 (m, 1 H), 0.92 (s, 6 H).

1235865-77-6, As the paragraph descriping shows that 1235865-77-6 is playing an increasingly important role.

Reference£º
Patent; AbbVie Inc.; Catron, Nathaniel; Lindley, David; Miller, Jonathan M.; Schmitt, Eric A.; Tong, Ping; US10213433; (2019); B2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

Analyzing the synthesis route of 2-((1H-Pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid

1235865-77-6, The synthetic route of 1235865-77-6 has been constantly updated, and we look forward to future research findings.

The sulfonamide (compound 3, 158.9 g), DMAP (123.7 g), EDCI (126.5 g) and dichloromethane (3678 mL) were combined at 25C (reactor I). In a second reactor (reactor II), the benzoic acid derivative (compound 2, 340.0 g), Et3N (140 mL) and dichloromethane (2936 mL) were combined and stirred for 15 minutes. The resulting acid solution (reactor II) was slowly added to the suspension of the sulfonamide (reactor I) within 120 minutes and reaction mixture agitated until reaction completion. After 22 hours the reaction mixture was washed with 10% acetic acid solution twice (2×2056 mL). The lower organic layer was diluted with more dichloromethane (882 mL) and methanol (146 mL), before separation of the organic layer. After phase separation the organic layer was washed with 5% aq. NaHCO3 (2059 mL) and then with 5% NaCl solution (2059 mL) at room temperature. The lower organic layer was separated and the concentrated to dryness, resulting a yellow solid. Dichloromethane (2014 mL) and methanol (206 mL) were added, the suspension was heated to 38C under stirring. Ethyl acetate (1840 mL) was added slowly within 40 minutes to the yellow solution. Heating was turned off and the suspension was cooled to 0-5 C and stirred at 5C overnight. The filtrated product was washed with Ethyl acetate (735 ml) and dried under vacuum (100 mbar) at 50C overnight to yield Venetoclax as yellow solid (273.6 g; 62.5 %, HPLC purity 95.36 A%).

1235865-77-6, The synthetic route of 1235865-77-6 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; ASSIA CHEMICAL INDUSTRIES LTD.; TEVA PHARMACEUTICALS USA, INC.; POTARINE JUHASZ, Zsuzsa; STRUBA, Szabolcs; NEMETHNE RACZ, Csilla; TOTH, Zoltan Gabor; SZILAGYI, Andrea; KERTI-FERENCZI, Renata; MOLNAR, Sandor Janos; PASZTOR-DEBRECZENI, Nora; HAJKO, Janos; (100 pag.)WO2017/156398; (2017); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

Simple exploration of 2-((1H-Pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid

1235865-77-6, 2-((1H-Pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

General procedure: 2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazin-1-yl)benzoic acid (5) was synthesized by the method reported. [Nat Med. 2013, 19(2): 202-8] To a solution of compound 5 (100 mg, 0.175 mmol) in anhydrous dichloromethane, compound 4g (68 mg, 0.175 mmol), EDCI (167 mg, 0.875 mmol) and DMAP (25.6 mg, 0.21 mmol) were added. Afterwards, the mixture solution was stirred for 24 h at room temperature. Completion of the reaction was confirmed by TCL. The reaction mixture was washed with HCl (1 M), NaHCO3 saturated solution and brine, concentrated and purified to afford 6g (160 mg, 85% yield) as a yellow solid., 1235865-77-6

Reference£º
Article; Zhou, Ruolan; Fang, Shaoyu; Zhang, Minmin; Zhang, Qingsen; Hu, Jian; Wang, Mingping; Wang, Chongqing; Zhu, Ju; Shen, Aijun; Chen, Xin; Zheng, Canhui; Bioorganic and Medicinal Chemistry Letters; vol. 29; 3; (2019); p. 349 – 352;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

New learning discoveries about 1235865-77-6

As the paragraph descriping shows that 1235865-77-6 is playing an increasingly important role.

In a 100-mL three necked round bottom flask equipped with magnetic stirrer, thermometer, condenser, charged 15 mL of 2-[(1H-Pyrrolo[2,3-b]pyridine-5-yl)oxy]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl]methyl]piperazin-1-yl]benzoic acid in THF (assay: 1 g, 1.75 mmol), heated up to 50-55C and 0.4 mL (5.25 mmol) trifluoroacetic acid in THF (2 mL) was added. The reaction mixture was stirred for 30 min at 50-55C and n-heptane (25 mL) was added dropwise at this temperature. The reaction mixture was cooled to 0-5C, stirred for 30 min and filtered. The wet cake was washed with n-heptane (2.5 mL) and dried under vacuum at 40- 45C overnight to obtain desired compound (assay: 0.85 g, 85%, TFA: 14.8%)., 1235865-77-6

As the paragraph descriping shows that 1235865-77-6 is playing an increasingly important role.

Analyzing the synthesis route of 1235865-77-6

1235865-77-6, The synthetic route of 1235865-77-6 has been constantly updated, and we look forward to future research findings.

EXAMPLE 1 J (3.39 g), EXAMPLE 2A (1.87 g), l-ethyl-3-[3-(dimethylamino)propyl]- carbodiimide hydrochloride (2.39 g), and 4-dimethylaminopyridine (1.09 g) were stirred in CH2C12 (40 mL) for 24 hours. The residue was purified by flash chromatography, eluting with 25-100%o ethyl acetate in hexanes, then 10% methanol in ethyl acetate with 1% acetic acid to give the product as a white solid. .H NMR (300MHz, dimethylsulfoxide-d6) 11.65 (brs, 1H), 8.55 (br s, 1H), 8.04 (d, 1H), 7.89 (dd, 1H), 7.51 (m, 3H), 7.33 (d, 2H), 7.08 (m, 1H), 7.04 (d, 2H), 6.68 (dd, 1H), 6.39 (d, 1H), 6.19 (d, 1H), 3.84 (m, 1H), 3.30 (m, 4H), 3.07 (m, 4H), 2.73(m, 2H), 2.18 (m, 6H), 1.95 (m, 2H), 1.61 (dd, 2H), 1.38 (m, 2H), 1.24 (m, 4H), 0.92 (s, 6H).

1235865-77-6, The synthetic route of 1235865-77-6 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; ABBOTT LABORATORIES; TAO, Zhi-Fu; WANG, Xilu; SOUERS, Andrew J.; CATRON, Nathaniel D.; SULLIVAN, Gerard; WO2011/150016; (2011); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

Brief introduction of 1235865-77-6

The synthetic route of 1235865-77-6 has been constantly updated, and we look forward to future research findings.

Compound IX 20.3 g (0.064 mol), 15.8 g (0.13 mol) DMAP, 20.9 g were added to a 2 L reaction flask.(0.11 mol) EDCI and 500 mL dichloromethane (DCM),The system was stirred at 20 C.A solution of 37.5 g (0.064 mol) of compound VIII and 23.7 g (0.23 mol) of triethylamine and 200 mL of dichloromethane prepared in advance was slowly added dropwise to the above system.After the completion of the dropwise addition, the mixture was stirred at 20 C for 3 hours, and then controlled by HPLC or TLC. The starting material was completely reacted.To the system was added 14.1 g of N,N’-dimethylethylenediamine.The system is heated to 35 C and stirring is continued.After the temperature is stable, add 200 mL of 12% acetic acid solution.After stirring for 10 min, the layers were separated, and the organic layer was washed with 5% sodium hydrogen carbonate solution (200 mL) and then washed with 5% sodium chloride solution (200 mL).The organic layer was dried, filtered, and evaporated to dryness.After the system is heated to 30 C, the methanol solution is added dropwise.After the system is clarified, start to cool down to 0-5 C, and stir for 1 h.After filtration, the cake was dried to give a white solid compound I about 50.8 g.The yield is 91.4%,, 1235865-77-6

The synthetic route of 1235865-77-6 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; Jiangsu Zhongbang Pharmaceutical Co., Ltd.; Huang Shuang; Yang Jian; Wu Xiaogang; Shi Lingyun; Liu Liping; (21 pag.)CN108997333; (2018); A;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

Downstream synthetic route of 1235865-77-6

As the paragraph descriping shows that 1235865-77-6 is playing an increasingly important role.

In 25 ml water compound is added in the bottle (J) 100 mg, EDCI67mg, dichloromethane 10 ml, reaction solution stirring 30 minutes, the compound is added (K) (in accordance with WO2012058392 method preparation) 55 mg, finally adding catalytic DMAP, reaction solution adding stirring reaction sleepovers, to splines end of the detection reaction TLC solvent, ABT-199 HPLC purified to get the pure product 98 mg, yield 65%., 1235865-77-6

As the paragraph descriping shows that 1235865-77-6 is playing an increasingly important role.

Reference£º
Patent; Nanjing Acesys Pharmatech Co., Ltd; GE, MIN; XU, YUNLEI; (8 pag.)CN104370905; (2016); B;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

Brief introduction of 1235865-77-6

The synthetic route of 1235865-77-6 has been constantly updated, and we look forward to future research findings.

Example 130D 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-[(3-nitro-4-{[(3R)-1-tetrahydro-2H-pyran-4-ylpyrrolidin-3-yl]amino}phenyl)sulfonyl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide To a solution of EXAMPLE 3J (90 mg), EXAMPLE 130C (64.2 mg), triethylamine (0.077 ml), N,N-dimethylpyridin-4-amine (38.5 mg) in a mixture of dichloromethane (5 ml) and N,N-dimethylformamide (0.5 ml) was added N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine, hydrochloric acid (60.4 mg) and the mixture was stirred 18 hours. This was concentrated on high vacuum and the crude was purified by reverse phase chromatography with ammonium acetate buffer/acetonitrile. 1H NMR (500 MHz, pyridine-d5) delta 13.03 (s, 1H), 9.27 (d, 1H), 8.59 (d, 1H), 8.43 (d, 1H), 8.37 (dd, 1H), 8.11 (d, 1H), 7.65-7.67 (m, 2H), 7.44 (d, 2H), 7.07 (d, 2H), 6.88 (d, 1H), 6.76 (dd, 1H), 6.54 (d, 1H), 6.48 (m, 1H), 4.06 (m, 1H), 3.98 (d, 2H), 3.35 (t, 2H), 3.07 (m, 4H), 2.73-2.80 (m, 4H), 2.68-2.72 (m, 1H), 2.36 (q, 1H), 2.11-2.30 (m, 9H), 1.97 (m, 2H), 1.62-1.71 (m, 3H), 1.48-1.58 (m, 2H), 1.39 (t, 2H), 0.94 (s, 6H)., 1235865-77-6

The synthetic route of 1235865-77-6 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; ABBOTT LABORATORIES; US2010/305122; (2010); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

Analyzing the synthesis route of 1235865-77-6

The synthetic route of 1235865-77-6 has been constantly updated, and we look forward to future research findings.

Example 1O 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-[(4-{[(2R)-1,4-dioxan-2-ylmethyl]amino}-3-nitrophenyl)sulfonyl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide EXAMPLE 1N (170 mg), EXAMPLE 1J (340 mg), 1-ethyl-3-[3-(dimethylamino)propyl]-carbodiimide hydrochloride (150 mg), and 4-dimethylaminopyridine (130 mg) were stirred in CH2Cl2 (5 mL) overnight. N1,N1-dimethylethane-1,2-diamine (0.19 mL) was then added and the mixture was stirred for 90 minutes. Dichloromethane (15 mL) was added, and the reaction mixture was washed with 10% acetic acid:0.75% NaCl in water (2*12 mL). The combined aqueous layers were back-extracted with dichloromethane, and the combined organics were washed with brine, and dried over Na2SO4. After filtration and concentration, the crude material was chromatographed on silica gel with 3/7 dichloromethane/ethyl acetate. The material was then chromatographed on silica gel with 1.5-2.5% CH3OH in dichloromethane. The material was triturated with CH3CN to afford the title compound. 1H NMR (400 MHz, dimethylsulfoxide-d6) delta ppm 11.65 (s, 1H), 8.55 (t, 1H), 8.54 (d, 1H), 8.01 (d, 1H), 7.81 (dd, 1H), 7.50 (m, 3H), 7.32 (d, 2H), 7.07 (d, 1H), 7.02 (d, 2H), 6.66 (dd, 1H), 6.37 (m, 1H), 6.18 (d, 1H), 3.77 (m, 3H), 3.63 (m, 2H), 3.47 (m, 2H), 3.31 (m, 2H), 3.06 (br m, 4H), 2.74 (br s, 2H), 2.19 (br m, 4H), 2.13 (br m, 2H), 1.94 (br m, 2H), 1.37 (t, 2H), 0.90 (s, 6H)., 1235865-77-6

The synthetic route of 1235865-77-6 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; Tao, Zhi-Fu; Wang, Xilu; Wendt, Michael; Souers, Andrew; Judd, Andrew; Kunzer, Aaron; Sullivan, Gerard; US2014/275082; (2014); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics