Triazoles

Application of 4928-87-4, These common heterocyclic compound, 4928-87-4, name is 1,2,4-Triazole-3-carboxylic acid, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

A mixture of 5-((lR,3s,5S)-8-azabicyclo[3.2.1]octan-3-yl)-3-(6-phenylpyridin-3-yl)- 8H-pyrazolo[l,5-a]pyrrolo[3,2-e]pyrimidine (0.19 mmol), lH-l,2,4-triazole-3-carboxylic acid (21.7mg, 0.19 mmol), EDC (58.6 mg, OJ lmmol), HOBt (25.9 mg, 0.19 mmol) and DIEA (200 uL, 1.15 mmol) in DMF (5 mL) was stirred at room temperature for 2 h. Purification with prep-LC provided ((lR,3s,5S)-3-(3-(6-phenylpyridin-3-yl)-8H-pyrazolo[l,5- a]pyrrolo[3,2-e]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octan-8-yl)(4H-l,2,4-triazol-3- yl)mefhanone.

The synthetic route of 4928-87-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME CORP.; MENG, Zhaoyang; PATEL, Mehul, F.; SIDDIQUI, M. Arshad; REDDY, Panduranga Adulla, P.; NAN, Yang; WO2013/16164; (2013); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

These common heterocyclic compound, 4928-88-5, name is Methyl 1H-1,2,4-triazole-3-carboxylate, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. Formula: C4H5N3O2

EXAMPLE 7 A mixture of methyl 1,2,4-triazole-3-carboxylate (26.4 g, 0.21 mole) and beta-D-ribofuranosyl-1,2,3,5-tetraacetate (60.2 g, 0.19 mole) was melted and then 1.8 g (0.05 eq.) of p-toluenesulfonic acid was added thereto. The reaction mixture was reacted for 5 hours, while maintaining the temperature of the reaction mixture at 95+-5¡ã C. And then, the reaction mixture was crystallized with 300.8 nm of methanol to give 61.7 g of 1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-1,2,4-triazole-3-carboxylic acid methyl ester (yield: 85percent).

The synthetic route of Methyl 1H-1,2,4-triazole-3-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Lee, Tai-Au; Park, Nam-Jin; Khoo, Ja-Heouk; Lee, Byung-Cheol; US2003/120064; (2003); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 584-13-4, name is 4H-1,2,4-Triazol-4-amine, A new synthetic method of this compound is introduced below., SDS of cas: 584-13-4

5-(4H-l,2,4~Triazol-4-yIaraino)-4t-fluorobiphenyl-2-carbonitrile (CAB06062)To a solution of 4/f-l ,2,4-triazol-4-amme (1.711 g, 20.35 mmol) in DMSO (30 mL) was added KOtBu (2.28 g, 20.35 mmol). The mixture was stirred for 0.5 h at room temperature before CAB06058 (2.19 g, 10.17 mmol) was added and stirring was continued for 1 hour. The mixture was poured into crushed ice and neutralized with 2M KHSO4 solution. The precipitate was filtered off, washed with water and reciystallised from ElOAc/n-hexane to afford CAB06062 (2,07 g, 73%) as a light yellow crystalline solid. Mp- 231-234 0C; 1H NMR (400 MHz, DMSO-rfbeta) delta 6.50 (d, .1 = 2 4 Hz3 IH), 6.58 (dd, J = 8.6, 2.4 Hz, IH)3 7.32-738 (m. 2H), 7.51-7.58 (m, 2H), 7.80 (d, J = 8.6 Hz, IH), 8.86 (s, 2H)5 1032 (s, IH); LRMS (ES+): mfz 280.1 (100%, [M+H]+); HRMS (ES+) calcd for Ci5HnFN5 [M+H]+: 280.0993, found 280.0982; Anal Calcd for C15Hj0FN5: C, 64.51 ; H, 3.61; N, 25.08 Found C, 64.4; H3 3.57; N, 24.8.

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; STERIX LIMITED; WOO, Lok Wai Lawrence; BUBERT, Christian; WOOD, Paul Michael; PUTEY, Aurelien; PUROHIT, Atul; POTTER, Barry Victor Lloyd; WO2011/23989; (2011); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Synthetic Route of 16681-70-2, The chemical industry reduces the impact on the environment during synthesis 16681-70-2, name is 1H-[1,2,3]Triazole-4-carboxylic acid, I believe this compound will play a more active role in future production and life.

Preparation 14 (2S,4R)-5-(4-Bromophenyl)-2-hydroxymethyl-2-methyl-4-[(1H-[1,2,3]triazole-4-carbonyl)amino]pentanoic Acid (2S,4R)-5-(4-bromophenyl)-4-t-butoxycarbonylamino)-2-(hydroxymethyl)-2-methylpentanoic acid (1.0 g, 2.4 mmol) was combined with MeCN (20 mL). 4N HCl in dioxane 1.8 mL, 7.2 mmol) was added. The resulting mixture was stirred for 30 minutes then concentrated under reduced pressure. 1H-[1,2,3]Triazole-4-carboxylic acid (272 mg, 2.4 mmol) and HATU (959 mg, 2.5 mmol) were combined in DMF (2 mL) and stirred for 10 minutes. DIPEA (1.3 mL, 7.2 mmol) and Compound 1 in DMF (2 mL) were added and the resulting mixture was stirred for 30 minutes then concentrated. The residue was purified by reverse phase chromatography (20-100% MeCN in water) to yield the title compound (287 mg).

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, 1H-[1,2,3]Triazole-4-carboxylic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Fleury, Melissa; Hughes, Adam D.; US2014/45906; (2014); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Synthetic Route of 118863-62-0, Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 118863-62-0, name is 3-(4-Bromophenyl)-1H-[1,2,4]triazole, This compound has unique chemical properties. The synthetic route is as follows.

Into a 1000 mL 3-necked flask, was placed a solution of ethyl 4- bromobenzenecarboximidoate (54.0 g, 237 mmol) in xylene (500 mL). To the mixture was added NH2NHCHO (14.22 g, 237 mmol). The resulting solution was heated to reflux overnight. The reaction mixture was cooled in an ice bath and filtered. The solid was washed with 700 mL of petroleum ether and dried in an oven under reduced pressure to afford 3-(4-bromophenyl)-lH- 1,2,4-triazole (crude) as a white solid.Into a 500 mL 3-necked flask was placed a solution of 3-(4-bromophenyl)-lH- 1,2,4-triazole (2.24 g, 10.0 mmol) in TetaF (200 mL). To this was added TEA (1.10 g, 10.9 mmol). To the mixture was added BoC2O (2.39 g, 11.0 mmol). The resulting solution was stirred overnight at room temperature. The mixture was evaporated, and the residue was purified by chromatography (1 :20 EtOAc/PE) to provide tert-butyl 3-(4-bromophenyl)-4H-l,2,4-triazole- 4-carboxylate as a white solid.Into a 2000 mL 3-necked flask was placed a solution of tert-butyl 3-(4- bromophenyl)-4H-l ,2,4-triazole-4-carboxylate (80.0 g, 247 mmol) in CH2Cl2 (800 mL). To the mixture was added TFA (400 mL). The resulting solution was stirred at room temperature for 1 h. The reaction was evaporated to provide 3-(4-bromophenyl)-l//-l,2,4-triazole as a white solid. 1H NMR (300 MHz, DMSOd6) 8.52 (s, IH), 7.97 (d, 2H), 7.69 (d, 2H). Calc’d for C8H7BrN3 [M+H]+ 224, found 224.

The chemical industry reduces the impact on the environment during synthesis 3-(4-Bromophenyl)-1H-[1,2,4]triazole. I believe this compound will play a more active role in future production and life.

Reference:
Patent; MERCK & CO., INC.; WO2008/156726; (2008); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 27996-86-7, name is 4-[1,2,4]Triazol-1-yl-benzaldehyde, belongs to Triazoles compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 27996-86-7, COA of Formula: C9H7N3O

A mixture of alpha ionone (1.152 g, 1.23 ml, 6 mmol), 4-(1H-1,2,4-triazol-1-yl) benzaldehydes (0.865 g, 5 mmol), cetyltrimethyl ammonium bromide (0.070 g, 0.5 mmol), sodium hydroxide (0.600 g, 15 mmol) and water (25 ml) was stirred at room temperature for 24 h. Reaction progress was monitored by TLC and compound was extracted with ethyl acetate (2 ¡Á 50 ml). The combined organic extract was washed with water (2 ¡Á 50 ml), brine solution (50 ml), dried (Na2SO4) and the solvent was removed in vacuum. The crude product was purified by column chromatography (SiO2, 60-120 mesh). Elution with 10 % ethyl acetate in hexane furnished a pale yellow coloured solid (0.400g, 23%). Mp: 108-110OC; IR (KBr, cm-1): 2915, 1651 (C=O), 1598 (C=N); 1H NMR (CDCl3, 300 MHz): delta 0.88 (s, 3H), 0.95 (s, 3H), 1.22-1.29 (m, 1H), 1.43-1.52 (m, 1H), 1.60 (s, 3H), 2.07 (brs, 2H), 2.36 (d, J = 9 Hz, 1H), 5.53 (brs, 1H), 6.39 (d, J = 16 Hz, 1H), 6.85 (dd, J = 16, 9 Hz, 1H), 7.01 (d, J = 16 Hz, 1H), 7.63-7.74 (m, 5H), 8.11 (s, 1H), 8.60 (s, 1H); 13C NMR (CDCl3, 75 MHz): delta 22.92, 23.10, 26.90, 27.95, 31.25, 32.75, 54.67, 2¡Á120.13, 122.83, 125.72, 2¡Á129.72, 130.54, 131.93, 134.81, 137.99, 140.89, 141.16, 149.44, 152.81, 188.53; ESI-MS m/z: 348 [M+1]+; Analysis calculated for C22H25N3O: C, 76.05; H, 7.25; N, 12.09; Found: C, 76.05; H, 7.29; N, 12.03.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Article; Suryawanshi; Tiwari, Avinash; Kumar, Santosh; Shivahare, Rahul; Mittal, Monika; Kant, Padam; Gupta, Suman; Bioorganic and Medicinal Chemistry Letters; vol. 23; 10; (2013); p. 2925 – 2928;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

These common heterocyclic compound, 27996-86-7, name is 4-[1,2,4]Triazol-1-yl-benzaldehyde, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. Safety of 4-[1,2,4]Triazol-1-yl-benzaldehyde

A mixture of beta ionone (0.48 g, 0.507 ml, 2.5 mmol), 4-(1H-1,2,4-triazol-1-yl) benzaldehydes (0.346 g, 2 mmol), cetyltrimethyl ammonium bromide (0.028 g, 0.20 mmol), sodium hydroxide (0.240 g, 6 mmol) and water (10 ml) was stirred at room temperature for 24 h. Reaction progress was monitored by TLC and compound was extracted with ethyl acetate (2 ¡Á 30 ml). The combined organic extract was washed with water (2 ¡Á 30 ml), brine solution (25 ml), dried (Na2SO4) and the solvent was removed in vacuum. The crude product was purified by column chromatography (SiO2, 60-120 mesh). Elution with 10 % ethyl acetate in hexane furnished a yellow coloured solid (0.164 g, 24%). Mp: 103-104OC; IR (KBr, cm-1): 2929, 1643 (C=O), 1590 (C=N); 1H NMR (CDCl3, 300 MHz): delta 1.05 (s, 6 H, CH3-8? and CH3-9?), 1.41-1.45 (m, 2H, CH2-5?), 1.55-1.61 (m, 2H, CH2-4?), 1.77 (s, 3H, CH3-7?), 2.04 (t, J = 6 Hz, 2 H, H-3?), 6.42 (d, J = 16 Hz, 1H, H-4), 6.96 (d, J = 16 Hz, 1H, H-2), 7.48 (d, J = 16 Hz, 1H, H-5), 7.61 (d, J = 16 Hz, 1H, H-1), 7.67 (brs, 4H, H-2?, H-3?, H-5? and H-6?), 8.06 (s, 1H, H-3???), 8.55 (s, 1H, H-5???); 13C NMR (CDCl3, 75 MHz): delta 18.86, 21.89, 2¡Á28.87, 33.76, 34.18, 39.85, 2¡Á120.08, 126.64, 129.35, 2¡Á129.63, 134.87, 136.50, 137.26, 137.89, 140.69, 140.82, 143.54, 152.78, 188.66; ESI-MS m/z: 348 [M+1]+; Analysis calculated for C22H25N3O: C, 76.05; H, 7.25; N, 12.09; Found: C, 76.10; H, 7.19; N, 12.11.

The synthetic route of 4-[1,2,4]Triazol-1-yl-benzaldehyde has been constantly updated, and we look forward to future research findings.

Reference:
Article; Suryawanshi; Tiwari, Avinash; Kumar, Santosh; Shivahare, Rahul; Mittal, Monika; Kant, Padam; Gupta, Suman; Bioorganic and Medicinal Chemistry Letters; vol. 23; 10; (2013); p. 2925 – 2928;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 16681-65-5, name is 1-Methyl-1H-1,2,3-triazole, A new synthetic method of this compound is introduced below., Product Details of 16681-65-5

n-BuLi (1.23 M in hexanes, 1.1 mL, 1.35 mmol) was added dropwise to a stirred slurry of 1-methyl-1,2,3-triazole (112 mg, 1.35 mmol) in THF (1 mL) at -40 C. under nitrogen. After stirring for another 30 minutes, the mixture was treated dropwise with a solution of (4-chloro-3-isopropoxy-2-methoxyquinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)methanone (252 mg, 0.67 mmol, Intermediate 27) in THF (5 mL). The reaction was allowed to warm to room temperature over 1 hour. The reaction was then quenched with saturated aqueous NH4Cl. The mixture was poured into a separatory funnel and extracted with DCM (4*60 mL). The organics were combined, washed with brine, dried (Na2SO4), filtered and concentrated to dryness to afford a light yellow oil. The crude material was purified by FCC (1-7.5% MeOH/DCM) followed by reverse-phase HPLC (acetonitrile/water+NH4OH) to provide the title compound as a white solid. 1H NMR (400 MHz, CDCl3) delta ppm 8.08 (d, J=2.2 Hz, 1H), 7.78 (d, J=8.7 Hz, 1H), 7.33 (dd, J=8.6, 2.2 Hz, 1H), 7.18 (s, 1H), 6.18 (s, 1H), 4.74-4.67 (m, 1H), 4.32 (s, 1H), 4.13 (s, 3H), 3.94 (s, 3H), 3.39 (s, 3H), 2.32 (s, 3H), 1.39 (d, J=6.2 Hz, 6H). MS (ESI): mass calcd. for C22H25ClN6O3, 456.2. m/z found, 457.0 [M+H]+. [4-Chloro-2-methoxy-3-(1-methylethoxyl)quinolin-6-yl](1,2-dimethyl-1H-imidazol-5-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol was purified by chiral SFC (Stationary phase: CHIRALPAK AD-H 5 muM 250*20 mm, Mobile phase: 70% CO2, 30% MeOH/iPrOH 50/50 v/v+(0.3% iPrNH2)) to give 2 enantiomers. The first eluting enantiomer was Example 80b: 1H NMR (400 MHz, CDCl3) delta ppm 8.09 (d, J=2.2 Hz, 1H), 7.77 (d, J=8.7 Hz, 1H), 7.32 (dd, J=8.7, 2.2 Hz, 1H), 7.17 (s, 1H), 6.17 (s, 1H), 4.75-4.66 (m, 1H), 4.36 (s, 1H), 4.13 (s, 3H), 3.94 (s, 3H), 3.39 (s, 3H), 2.32 (s, 3H), 1.39 (d, J=6.2 Hz, 6H). MS (ESI): mass calcd. for C22H25ClN6O3, 456.2. m/z found, 457.2 [M+H]+ and the second eluting enantiomer was Example 80c: 1H NMR (400 MHz, CDCl3) delta ppm 8.06 (d, J=2.2 Hz, 1H), 7.80 (d, J=8.7 Hz, 1H), 7.35-7.32 (m, 1H), 7.21 (s, 1H), 6.24 (s, 1H), 4.74-4.67 (m, 1H), 4.13 (s, 3H), 3.95 (s, 3H), 3.52 (s, 1H), 3.42 (s, 3H), 2.37 (s, 3H), 1.39 (d, J=6.2 Hz, 6H). MS (ESI): mass calcd. for C22H25ClN6O3, 456.2. m/z found, 457.2 [M+H]+.

The synthetic route of 16681-65-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; JOHNSON & JOHNSON; LEONARD, KRISTI A.; BARBAY, KENT; EDWARDS, JAMES P.; KREUTTER, KEVIN D.; KUMMER, DAVID A.; MAHAROOF, UMAR; NISHIMURA, RACHEL; URBANSKI, MAUD; VENKATESAN, HARIHARAN; WANG, AIHUA; WOLIN, RONALD L.; WOODS, CRAIG R.; FOURIE, ANNE; XUE, XIAOHUA; CUMMINGS, MAXWELL D.; MCCLURE, KELLY; TANIS, VIRGINIA; US2015/111870; (2015); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Synthetic Route of 16681-70-2, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 16681-70-2 name is 1H-[1,2,3]Triazole-4-carboxylic acid, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

[0760] lH-1,2,3-triazole-4-carboxylic acid (2.6 mg, 23f.tmol) was combined with HATU (9.6 mg, 25 flillOl) in DMF(3.0 mL) and stirred at room temperature for 15 minutes.Compound 2 (13 mg, 29 f.tmol) was dissolved in DIPEA (12f.LL, 69 f.tmol) and combined with the activated acid solution.The mixture was stirred at room temperature for 15 minutes,after which time LCMS indicated desired product formation.The solvent was removed in vacuo and the crude residue waspurified by reverse phase chromatography to yield Compoundb (0.8 mg) as a TFA salt. MS m/z [M+Ht calc’d forC25H27ClF3N50 3 , 538.18. found 538.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1H-[1,2,3]Triazole-4-carboxylic acid, and friends who are interested can also refer to it.

Reference:
Patent; THERAVANCE BIOPHARMA R&D IP, LLC; Fleury, Melissa; Beausoliel, Anne-Marie; Hughes, Adam D.; Long, Daniel D.; Wilton, Donna A.A.; US2015/210690; (2015); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Synthetic Route of 13273-53-5, A common heterocyclic compound, 13273-53-5, name is 4-Bromo-1-methyl-1H-1,2,3-triazole, molecular formula is C3H4BrN3, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

Step 1. (S)-(6-bromo-5-(2,5-difluoro-4-nitrophenoxy)-2-methyl-3,4-dihydroquinoliii-l(2H)- yl)(cyclopropyl)methanone and (S)-(6-bromo-5-(4,5-difluoro-2-nitrophenoxy)-2-methyl-3,4- dihydroquinolin-l(2H)-yl)(cyclopropyl)methanone [0568] A 100-mL, 3-necked round-bottom flask was charged with a solution of (S)-(6-bromo-5- hydroxy-2-methyl-3,4-dihydroquinolin-l(2H)-yl)(cyclopropyl)methanone (2.00 g, 6.45 mmol) in tetrahydrofuran (20 mL). Potassium tert-butoxide (0.797 g, 7.10 mmol) was added in portions at 0 C and the mixture stirred for 5 minutes. 1 ,2,4-Trifluoro-5-nitrobenzene (1.72 g, 9.71 mmol) was then added, and the resulting mixture stirred at 0 C for 3 h. Hydrochloric acid (I aqueous, 10 mL) was added, and the aqueous phase was separated and extracted with ethyl acetate (2 x 15 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified via column chromatography on silica gel (eluting with 1 : 10, ethyl acetate/petroleum ether) to afford a mixture of (S)-(6-bromo-5-(2,5-difluoro-4-nitrophenoxy)-2- methyl-3,4-dihydroquinolin-l(2H)-yl)(cyclopropyl)methanone and (S)-(6-bromo-5-(4,5-difluoro-2- nitrophenoxy)-2-methyl-3,4-dihydroquinolin-l(2H)-yl)(cyclopropyl)methanone (2.1 g, 70%) as yellow oil. MS (ESI, pos. ion) m/z 467,469[M+H]+ Step 2. (S)-(5-(4-amino-2,5-difluorophenoxy)-6-bromo-2-methyl-3,4-dihydroquinoliii-l(2H)- yl)(cyclopropyl)methanone and (S)-(5-(2-amino-4,5-difluorophenoxy)-6-bromo-2-methyl-3,4- dihydroquinolin-l(2H)-yl)(cyclopropyl)methanone [0569] A 100-mL, round-bottom flask was charged with a mixture of (S)-(6-bromo-5-(2,5-difiuoro- 4-nitrophenoxy)-2-methyl-3,4-dihydroquinolin- 1 (2H)-yl)(cyclopropyl)methanone and (S)-(6- bromo-5-(4,5-difiuoro-2-nitrophenoxy)-2-methyl-3,4-dihydroquinolin-l(2H)- yl)(cyclopropyl)methanone (2.1 g, 4.49 mmol), iron powder (1.26 g, 22.5 mmol), ammonium chloride (0.476 g, 8.90 mmol), tetrahydrofuran (10 mL), ethanol (10 mL), and water (3 mL). The resulting mixture stirred overnight at 80 C. After cooling to room temperature, the reaction mixture was filtered, and the filtrate was extracted with ethyl acetate (2 x 15 mL). The combined organic layers were concentrated under vacuum to afford a mixture of (S)-(5-(4-amino-2,5- difluorophenoxy)-6-bromo-2-methyl-3,4-dihydroquinolin- 1 (2H)-yl)(cyclopropyl)methanone and (S)-(5-(2-amino-4,5-difluorophenoxy)-6-bromo-2-methyl-3,4-dihydroquinolin-l(2H)- yl)(cyclopropyl)methanone (1.8 g, 96%) as brown oil, which was directly used in next step without further purification. MS (ESI, pos. ion) m/z 437,439[M+H]+ Step 3. (S)-(6-bromo-5-(3,4-difluorophenoxy)-2-methyl-3,4-dihydroquinolin-l(2H)- yl)(cyclopropyl)methanone and (S)-(6-bromo-5-(2,5-difluorophenoxy)-2-methyl-3,4- dihydroquinolin-l(2H)-yl)(cyclopropyl)methanone [0570] A 100-mL, round-bottom flask was charged with a mixture of (S)-(5-(2-amino-4,5- difluorophenoxy)-6-bromo-2-methyl-3,4-dihydroquinolin- 1 (2H)-yl)(cyclopropyl)methanone and (S)-(5-(4-amino-2,5-difluorophenoxy)-6-bromo-2-methyl-3,4-dihydroquinolin-l(2H)- yl)(cyclopropyl)methanone (1.8 g, 4.12 mmol) and N,N-dimethylformamide (10 mL). A solution of tert-butyl nitrite (1.2 g, 11.64 mmol) in N,N-dimethylformamide (10 mL) was added dropwise, and the resulting solution stirred for 4 h at 50 C. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (100 mL). The organic layer was washed with water (3 x 20 mL) and brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified via column chromatography on silica gel (eluting with 1 : 10, ethyl acetate/petroleum ether) to afford a mixture of (S)-(6-bromo-5-(3,4-difluorophenoxy)-2-methyl-3,4- dihydroquinolin- 1 (2H)-yl)(cyclopropyl)methanone and (S)-(6-bromo-5-(2,5-difluorophenoxy)-2- methyl-3,4-dihydroquinolin-l(2H)-yl)(cyclopropyl)methanone (0.600 g, 35%) as yellow oil. MS (ESI, pos. ion) m/z 422,424[M+H]+. Step 2. (S)-cyclopropyl(5-(3,4-difluorophenoxy)-2-methyl-6-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)-3,4-dihydroquinolin-l(2H)-yl)methanone and (S)-cyclopropyl(5-(2,5- difluorophenoxy)-2-methyl-6-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-3,4- dihydroquinolin-l(2H)-yl)methanone [0666] A mixture of (S)-(6-bromo-5-(3,4-difluorophenoxy)-2-methyl-3,4-dihydroquinolin-l(2H)- yl)(cyclopropyl)methanone and (S)-(6-bromo-5-(2,5-difiuorophenoxy)-2-methyl-3,4- dihydroquinolin-l(2H)-yl)(cyclopropyl)methanone (0.100 g, 0.24 mmol), bis(pinacolato)diboron (0.600 g, 2.37 mmol), [l, -bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (0.019 g, 0.02 mmol), and potassium acetate (0.046 mg, 0.47 mmol) in 1,4-dioxane (10 mL) was stirred overnight at 80 C. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (50 mL), washed with water (20 mL) and brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified by p…

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; BAIR, Kenneth W.; HERBERTZ, Torsten; KAUFFMAN, Goss Stryker; KAYSER-BRICKER, Katherine J.; LUKE, George P.; MARTIN, Matthew W.; MILLAN, David S.; SCHILLER, Shawn E. R.; TALBOT, Adam C.; WO2015/74064; (2015); A2;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics