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Chemistry
Organic Building Blocks
Aryls
benzyl
1-Ethynyl-3-(trifluoromethyl)benzene
Chemistry
Organic Building Blocks
Aryls
Trifluoromethyls Benzene Compounds Alkynes
benzyl
ethynylbenzene (trifluoromethyl)benzene

[ CAS No. 705-28-2 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
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3d Animation Molecule Structure of 705-28-2
Chemical Structure| 705-28-2
Chemical Structure| 705-28-2
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Quality Control of [ 705-28-2 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 705-28-2 ]

SDS Specification
Alternatived Products of [ 705-28-2 ]

Product Details of [ 705-28-2 ]

CAS No. :705-28-2 MDL No. :MFCD00467355
Formula : C9H5F3 Boiling Point : -
Linear Structure Formula :- InChI Key :PAHXLHWOHJTWRU-UHFFFAOYSA-N
M.W : 170.13 Pubchem ID :2778490
Synonyms :

Calculated chemistry of [ 705-28-2 ]

Physicochemical Properties

Num. heavy atoms : 12
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.11
Num. rotatable bonds : 1
Num. H-bond acceptors : 3.0
Num. H-bond donors : 0.0
Molar Refractivity : 39.38
TPSA : 0.0 Ų

Pharmacokinetics

GI absorption : Low
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.07 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.29
Log Po/w (XLOGP3) : 3.19
Log Po/w (WLOGP) : 3.92
Log Po/w (MLOGP) : 3.89
Log Po/w (SILICOS-IT) : 3.45
Consensus Log Po/w : 3.35

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -3.21
Solubility : 0.105 mg/ml ; 0.000619 mol/l
Class : Soluble
Log S (Ali) : -2.86
Solubility : 0.234 mg/ml ; 0.00138 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.36
Solubility : 0.0743 mg/ml ; 0.000437 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.98

Safety of [ 705-28-2 ]

Signal Word:Danger Class:3
Precautionary Statements:P210-P280 UN#:1993
Hazard Statements:H225-H302-H312-H332 Packing Group:Ⅱ
GHS Pictogram:

Application In Synthesis of [ 705-28-2 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 705-28-2 ]

[ 705-28-2 ] Synthesis Path-Downstream   1~88

  • 1
  • [ 705-28-2 ]
  • [ 33675-55-7 ]
YieldReaction ConditionsOperation in experiment
78% With iodine; sodium methylate In methanol at 20℃;
With iodine In ammonia
Reference： [1]Xu, Wei; Chen, Qing-Yun [Journal of Organic Chemistry, 2002, vol. 67, # 26, p. 9421 - 9427]
[2]Verploegh,M.C. et al. [Recueil des Travaux Chimiques des Pays-Bas, 1971, vol. 90, p. 765 - 778]
  • 2
  • [ 40230-93-1 ]
  • [ 705-28-2 ]
YieldReaction ConditionsOperation in experiment
96% With potassium carbonate In methanol; dichloromethane Inert atmosphere; Schlenk technique;
77% With potassium carbonate In ethanol at 20℃; for 16h; 13.b Add potassium carbonate (307 mg, 2. 22 mmol) to a solution of trimethyl- (3- trifluoromethylphenylethynyl)-silane (1. 07 g, 4. 42 mmol) in ethanol (15 mL). Stir at room temperature for 16 h. Neutralized with 10% aqueous hydrochloric acid solution. Add water and extract the product with hexanes. Evaportae hexanes slowly in a cool water bath (<15 °C) to give the title compound (580 mg, 77%). 1H NMR (300 MHz, CDC13) 6 3. 15 (s, 1H), 7. 45 (t, J = 7. 7 Hz, 1H), 7. 60 (d, J = 7. 7 Hz, 1H), 7. 66 (d, J = 7. 7 Hz, 1H), 7. 75 (s, 1H).
59.8% With potassium carbonate In methanol at 25℃; for 16h;
52% With N,N,N-tributylbutan-1-aminium fluoride In tetrahydrofuran at 0℃; for 1h;
(alkaline hydrolysis);
With sodium hydroxide In tetrahydrofuran; methanol; lithium hydroxide monohydrate at 20℃; for 0.5h;
With methanol; potassium carbonate In dichloromethane at 20℃; for 2h; Inert atmosphere;
0.5 g With ethanol; potassium carbonate at 20℃; for 18h; 50.2 Preparation of1-ethynyl-3-(trifluoromethyl)benzene To a solution of trimethyl((3-(trifluoromethyl)phenyl)ethynyl)silane (0.500 g, 2.06 mmol) in ethanol (10 mL) was added potassium carbonate (0.253g, 1.8 mmol) and the reaction mixture was stirred at RT for 18 h. The reaction mass was quenched in water, neutralized with dil. HC1 and extracted with hexane and concentrated to afford 0.200 g of the crude product which was further purified by column chromatography using silica (60- 120 mesh) eluting with pet. ether to afford 0.500 g of pure product. 1H NMR (300 MHz, DMSO d6): δ 4.41 (s, 1H), 7.64 (d, = 7.5 Hz, 1H), 7.77- 7.81 (m, 3H).
219 mg With N,N,N-tributylbutan-1-aminium fluoride In tetrahydrofuran at 20℃; for 4h;

Reference： [1]Ervik, Karina; Vidar Hansen, Trond [Tetrahedron Letters, 2022, vol. 100]
[2]Current Patent Assignee: ELI LILLY &amp; CO - WO2005/94822, 2005, A1 Location in patent: Page/Page column 31
[3]Austin, William B.; Bilow, Norman; Kelleghan, William J.; Lau, Kreisler S. Y. [Journal of Organic Chemistry, 1981, vol. 46, # 11, p. 2280 - 2286]
[4]Biletskyi, Bohdan; Kong, Lingyu; Tenaglia, Alphonse; Clavier, Hervé [Advanced Synthesis and Catalysis, 2021, vol. 363, # 10, p. 2578 - 2585]
[5]Oliver; Walton [Tetrahedron Letters, 1972, vol. 13, # 51, p. 5209 - 5212]
[6]Pasquini, Chiara; Bassetti, Mauro [Advanced Synthesis and Catalysis, 2010, vol. 352, # 14-15, p. 2405 - 2410]
[7]Miersch, Anne; Hilt, Gerhard [Chemistry - A European Journal, 2012, vol. 18, # 32, p. 9798 - 9801]
[8]Current Patent Assignee: ICHNOS SCIENCES INC - WO2013/186692, 2013, A1 Location in patent: Page/Page column 116
[9]Cloutier, Mélissa; Roudias, Majdouline; Paquin, Jean-François [Organic Letters, 2019, vol. 21, # 10, p. 3866 - 3870]
  • 3
  • [ 401-06-9 ]
  • [ 705-28-2 ]
YieldReaction ConditionsOperation in experiment
80% With n-butyllithium In diethyl ether
With n-butyllithium
Reference： [1]Kodaira, Kazuo; Okuhara, Kunio [Bulletin of the Chemical Society of Japan, 1988, vol. 61, # 5, p. 1625 - 1632]
[2]Okuhara, K.; Kodaira, K. [Journal of Fluorine Chemistry, 1983, vol. 23, p. 497]
  • 4
  • [ 705-28-2 ]
  • [ 1079-66-9 ]
  • diphenyl-(3-trifluoromethyl-phenylethynyl)-phosphane [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% With copper(l) iodide; triethylamine In toluene at 20℃;
Reference： [1]Afanasiev, Vladimir V.; Beletskaya, Irina P.; Kazankova, Marina A.; Efimova, Irina V.; Antipin, Mikhail U. [Synthesis, 2003, # 18, p. 2835 - 2838]
  • 5
  • [ 705-28-2 ]
  • [ 152711-55-2 ]
  • 3-[4-(3-trifluoromethyl-phenyl)-[1,2,3]triazol-1-yl]-chromen-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium L-ascorbate In water; dimethyl sulfoxide at 20℃; for 12h;
Reference： [1]Sivakumar, Krishnamoorthy; Xie, Fang; Cash, Brandon M.; Long, Su; Barnhill, Hannah N.; Wang, Qian [Organic Letters, 2004, vol. 6, # 24, p. 4603 - 4606]
  • 6
  • [ 705-28-2 ]
  • [ 817638-69-0 ]
  • 7-methoxy-3-[4-(3-trifluoromethyl-phenyl)-[1,2,3]triazol-1-yl]-chromen-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium L-ascorbate In water; dimethyl sulfoxide at 20℃; for 12h;
Reference： [1]Sivakumar, Krishnamoorthy; Xie, Fang; Cash, Brandon M.; Long, Su; Barnhill, Hannah N.; Wang, Qian [Organic Letters, 2004, vol. 6, # 24, p. 4603 - 4606]
  • 7
  • [ 705-28-2 ]
  • [ 817638-73-6 ]
  • 6-bromo-3-[4-(3-trifluoromethyl-phenyl)-[1,2,3]triazol-1-yl]-chromen-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium L-ascorbate In water; dimethyl sulfoxide at 20℃; for 12h;
Reference： [1]Sivakumar, Krishnamoorthy; Xie, Fang; Cash, Brandon M.; Long, Su; Barnhill, Hannah N.; Wang, Qian [Organic Letters, 2004, vol. 6, # 24, p. 4603 - 4606]
  • 8
  • [ 705-28-2 ]
  • [ 817638-68-9 ]
  • 7-hydroxy-3-[4-(3-trifluoromethyl-phenyl)-[1,2,3]triazol-1-yl]-chromen-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium L-ascorbate In water; dimethyl sulfoxide at 20℃; for 12h;
Reference： [1]Sivakumar, Krishnamoorthy; Xie, Fang; Cash, Brandon M.; Long, Su; Barnhill, Hannah N.; Wang, Qian [Organic Letters, 2004, vol. 6, # 24, p. 4603 - 4606]
  • 9
  • [ 705-28-2 ]
  • [ 817638-74-7 ]
  • 8-ethoxy-3-[4-(3-trifluoromethyl-phenyl)-[1,2,3]triazol-1-yl]-chromen-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium L-ascorbate In water; dimethyl sulfoxide at 20℃; for 12h;
Reference： [1]Sivakumar, Krishnamoorthy; Xie, Fang; Cash, Brandon M.; Long, Su; Barnhill, Hannah N.; Wang, Qian [Organic Letters, 2004, vol. 6, # 24, p. 4603 - 4606]
  • 10
  • [ 705-28-2 ]
  • [ 817638-70-3 ]
  • acetic acid 2-oxo-3-[4-(3-trifluoromethyl-phenyl)-[1,2,3]triazol-1-yl]-2<i>H</i>-chromen-7-yl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium L-ascorbate In water; dimethyl sulfoxide at 20℃; for 12h;
Reference： [1]Sivakumar, Krishnamoorthy; Xie, Fang; Cash, Brandon M.; Long, Su; Barnhill, Hannah N.; Wang, Qian [Organic Letters, 2004, vol. 6, # 24, p. 4603 - 4606]
  • 11
  • [ 705-28-2 ]
  • [ 817638-71-4 ]
  • 7-diethylamino-3-[4-(3-trifluoromethyl-phenyl)-[1,2,3]triazol-1-yl]-chromen-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium L-ascorbate In ethanol; water at 4℃;
Reference： [1]Sivakumar, Krishnamoorthy; Xie, Fang; Cash, Brandon M.; Long, Su; Barnhill, Hannah N.; Wang, Qian [Organic Letters, 2004, vol. 6, # 24, p. 4603 - 4606]
  • 12
  • [ 705-28-2 ]
  • [ 817638-72-5 ]
  • 9-[4-(3-trifluoromethyl-phenyl)-[1,2,3]triazol-1-yl]-2,3,5,6-tetrahydro-1<i>H</i>,4<i>H</i>-11-oxa-3a-aza-benzo[<i>de</i>]anthracen-10-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium L-ascorbate In ethanol; water at 4℃;
Reference： [1]Sivakumar, Krishnamoorthy; Xie, Fang; Cash, Brandon M.; Long, Su; Barnhill, Hannah N.; Wang, Qian [Organic Letters, 2004, vol. 6, # 24, p. 4603 - 4606]
  • 13
  • [ 705-28-2 ]
  • [ 446312-35-2 ]
  • [ 851227-30-0 ]
YieldReaction ConditionsOperation in experiment
75% Stage #1: 1-ethynyl-3-trifluoromethylbenzene With potassium hexamethylsilazane In tetrahydrofuran; toluene at -78℃; for 0.5h; Stage #2: With 9-methoxy-9-BBN In tetrahydrofuran; hexane; toluene at -78℃; for 2h; Stage #3: [4-(3-iodo-5-isopropyl-4-methoxymethoxybenzyl)-3,5-dimethylphenoxy]acetic acid methyl ester With bis-triphenylphosphine-palladium(II) chloride In tetrahydrofuran; hexane; toluene for 12h; Heating;
Reference： [1]Nguyen, Ngoc-Ha; Apriletti, James W.; Baxter, John D.; Scanlan, Thomas S. [Journal of the American Chemical Society, 2005, vol. 127, # 13, p. 4599 - 4608]
  • 14
  • [ 2295-08-1 ]
  • [ 705-28-2 ]
  • 1-[(3-dimethylsilanyl-propyl)-dimethyl-silanyl]-ethynyl}-3-trifluoromethyl-benzene [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% Stage #1: 1-ethynyl-3-trifluoromethylbenzene With n-butyllithium In tetrahydrofuran at -70℃; for 0.5h; Stage #2: chlorodimethyl<3-(dimethylsilyl)propyl>silane In tetrahydrofuran for 2h; Heating;
Reference： [1]Mueller, Thomas; Margraf, Dominik; Syha, Yvonne [Journal of the American Chemical Society, 2005, vol. 127, # 31, p. 10852 - 10860]
  • 15
  • [ 705-28-2 ]
  • [ 80778-47-8 ]
  • [ 870010-39-2 ]
YieldReaction ConditionsOperation in experiment
94% With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 50℃;
Reference： [1]Fuerstner, Alois; Davies, Paul W. [Journal of the American Chemical Society, 2005, vol. 127, # 43, p. 15024 - 15025]
  • 16
  • [ 672299-20-6 ]
  • [ 705-28-2 ]
  • N6-methoxy-2-[3-(trifluoromethyl)phenyl]ethynyl}adenosine [ No CAS ]
YieldReaction ConditionsOperation in experiment
74% With triethylamine In N,N-dimethyl-formamide at 20℃; for 17h;
Reference： [1]Volpini, Rosaria; Dal Ben, Diego; Lambertucci, Catia; Taffi, Sara; Vittori, Sauro; Klotz, Karl-Norbert; Cristalli, Gloria [Journal of Medicinal Chemistry, 2007, vol. 50, # 6, p. 1222 - 1230]
  • 17
  • [ 95080-93-6 ]
  • [ 705-28-2 ]
  • [ 871676-36-7 ]
YieldReaction ConditionsOperation in experiment
With triethylamine In tetrahydrofuran at 0 - 20℃; 1.E.1 E. Preparation of a Compound of Formula (4c) in which R is 3-trifluoromethylphenyl Step 1- Preparation of a Compound of Formula (k) To a stirred solution of ethyl chlorooximidoacetate (6.68 g, 44.09 mmol) in tetrahydrofuran (90 mL) in an ice bath was added 3-(trifluoromethyl)phenylacetylene (5.0 g, 29.39 mmol) slowly, followed by triethylamine (8.19 mL, 58.78 mmol) dropwise. The resulting mixture was stirred at room temperature overnight, which was then filtered through a layer of silica gel (top) and anhydrous Na2SO4 (bottom), and washed with ethyl acetate. The filtrate was washed with water, the organic layer dried over sodium sulfate, and the solvent removed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:Hexanes=1:9) to afford ethyl 5-[3-(trifluoromethyl)phenyl]isoxazole-3-carboxylate.
Reference： [1]Current Patent Assignee: AMYGDALA NEUROSCIENCES INC - US2008/32995, 2008, A1 Location in patent: Page/Page column 22
  • 18
  • [ 705-28-2 ]
  • [ 615-43-0 ]
  • [ 221910-15-2 ]
YieldReaction ConditionsOperation in experiment
With copper(l) iodide; diethylamine In N,N-dimethyl-formamide at 20℃; for 18h; Intermediate 26: Ethyl 3-[3-(thfluoromethyl)phenyl]methyl}-1 H-indole-2- carboxylateTo a solution of 2-iodoaniline (5.4g, 24.5 mmol) in DMF (4OmL) was added 3- thfluoromethylphenyl acetylene (5.Og, 29.4mmol), Et2NH (15.2ml_, 146.9mmol), CuI (93mg, O.δmmol) and bis(triphenylphosphine)-palladium (II) acetate (183mg, 0.24mmol). The mixture was stirred at ambient temperature for 18 hours. The reaction was poured into saturated ammonium chloride (20OmL) and extracted with ether (2 x 15OmL). The combined ether was dried over magnesium sulfate and concentrated to afford 2-[3- (trifluoromethyl)phenyl]ethynyl}aniline (intermediate 26a, 6.8g) as a dark oil. Material used without further purification. 1 H NMR (400MHz, DMSO-d6); δ 8.03 (s, 1 H), 7.86 (d, 1 H), 7.69 (d, 1 H), 7.61 (t, 1 H), 7.23 (d, 1 H), 7.08 (t, 1 H), 6.71 (d, 1 H), 6.51 (t, 1 H), 5.65 (s, 2H); C15H10F3N1.
Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2008/28118, 2008, A1 Location in patent: Page/Page column 78
  • 19
  • [ 454-91-1 ]
  • P2O5 [ No CAS ]
  • [ 705-28-2 ]
Reference： [1]Journal of Chemical Research, Miniprint,1981,p. 3216 - 3245
  • 20
  • [ 454-91-1 ]
  • [ 705-28-2 ]
Reference： [1]Journal of the American Chemical Society,1963,vol. 85,p. 3492 - 3496
  • 21
  • [ 50-00-0 ]
  • [ 705-28-2 ]
  • [ 29053-62-1 ]
  • 4-{3-[3-(trifluoromethyl)phenyl]prop-2-yn-1-yl}-1,4-diazepane-1-carbaldehyde [ No CAS ]
YieldReaction ConditionsOperation in experiment
With copper diacetate In 1,4-dioxane at 80℃; for 4h; 2.1 A mixture of 1.28 g (10 mmol) of 1,4-diazepane-1-carbaldehyde and 0.33 g (11 mmol) of paraformaldehyde in 13 ml of dioxane is heated at 80° C. until a homogeneous solution is obtained. 1.70 g (10 mmol) of 3-trifluoromethylphenylacetylene in solution in 7 ml of dioxane and 1.81 g (10 mmol) of copper diacetate are added. The mixture is heated at 80° C. for 4 hours. It is cooled to ambient temperature and diluted with 75 ml of ethyl acetate. The organic phase is washed with 25 ml of 30% ammonia solution and with saturated aqueous sodium chloride solution. It is dried over sodium sulphate and evaporated to dryness. The residue is purified by chromatography on silica gel, eluding with a 98/2/0.2 then 96/4/0.4 and 94/6/0.6 mixture of dichloromethane, methanol and 30% ammonia, to give 2.67 g of product in the form of a yellow oil.
Reference： [1]Current Patent Assignee: SANOFI - US2007/27141, 2007, A1 Location in patent: Page/Page column 6
  • 22
  • [ 705-28-2 ]
  • [ 626-01-7 ]
  • [ 138781-90-5 ]
YieldReaction ConditionsOperation in experiment
95% With copper(l) iodide In diethylamine at 50℃; for 15h; 1-III To a 27 mL diethylamine solution of 3.0 g (13.7 mmoles) of iodoaniline, 52 mg (0.274 mmole) of copper iodide, and 96 mg (0.137 mmole) of dichlorobis(triphenyl-phosphine)palladium was added 3.5 g (20.5 mmoles) of 3-ethynyl-α,α,α-trifluorotoluene and the mixture was stirred for 15 hours at 50° C. Ethyl acetate was added to the reaction solution, the mixture was filtered, water was added to the filtrate, and the filtrate was extracted. The organic layer was sequentially washed with a saturated sodium hydrogencarbonate aqueous solution and saturated brine, and then dried with anhydrous magnesium sulfate. The solvent was removed under reduced pressure. The residue was purified by basic silica gel column chromatography, yielding 3.4 g (95 percent) of aniline compound. 71 mg (0.383 mmole) of 2-sulfobenzoic anhydride was added to a 2 mL toluene solution of 100 mg (0.383 mmole) of the aniline compound and the mixture was stirred for one hour at room temperature. The solvent was removed under reduced pressure and the residue was purified by thin-layer chromatography, yielding 68 mg (40 percent) of Compound 16-III.
Reference： [1]Current Patent Assignee: AJINOMOTO COMPANY INC - US2007/105899, 2007, A1 Location in patent: Page/Page column 73
  • 23
  • [ 705-28-2 ]
  • [ 540-37-4 ]
  • [ 869578-08-5 ]
YieldReaction ConditionsOperation in experiment
100% With copper(l) iodide In diethylamine at 50℃; 18-III 5.00 g (22.8 mmole) of 4-iodoaniline was dissolved in 40 mL of diethylamine; 4.29 mL (29.7 mmoles) of 3-ethynyl-α,α,α-trifluorotoluene, 160 mg (0.0228 mmole) of PdCl2 (PPh3)2, and 87 mg (0.456 mmole) of CuI were added, and the mixture was stirred overnight at 50° C. The solvent was removed, ethyl acetate was added to the residue, and the organic layer was sequentially washed with 1N HCl aqueous solution and 1N NaOH aqueous solution. The obtained organic layer was washed with saturated brine and dried with anhydrous sodium sulfate. The solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography, yielding a quantitative amount of aniline compound. 447 mg (1.83 mmole) of the obtained aniline compound was dissolved in CH2Cl2 and cooled to 0° C. Next, 0.409 mL (2.74 mmoles) of diethylaniline and 0.275 mL (2.19 mmoles) of phenyl chloroformate were added and the mixture was stirred for two hours at 0° C. After the reaction had ended, 1N HCl aqueous solution was added to the reaction solution, the mixture was extracted with ethyl acetate, and the obtained organic layer was washed with saturated brine and dried with anhydrous sodium sulfate. The solvent was removed under reduced pressure. The residue was washed with hexane, yielding 607 mg of phenylcarbamate compound. 76 mg (0.200 mole) of the obtained phenylcarbamate compound was dissolved in CHC13, 0.060 mL (0.400 mmole) of DBU and 0.031 mL (0.200 mmole) of ethyl nipecotate were added, and the mixture was stirred for two hours at room temperature. After the reaction had ended, 1N HCl aqueous solution was added to the reaction solution and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine and dried with anhydrous sodium sulfate. The solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography, yielding 79 mg of Embodiment Compound 32-III.
Reference： [1]Current Patent Assignee: AJINOMOTO COMPANY INC - US2007/105899, 2007, A1 Location in patent: Page/Page column 75
  • 24
  • [ 39806-90-1 ]
  • [ 705-28-2 ]
  • [ 951403-43-3 ]
Reference： [1]Heterocycles,2007,vol. 71,p. 1967 - 1974
  • 25
  • [ 705-28-2 ]
  • [ 6647-97-8 ]
  • [ 951403-42-2 ]
Reference： [1]Heterocycles,2007,vol. 71,p. 1967 - 1974
  • 26
  • [ 6427-66-3 ]
  • [ 705-28-2 ]
  • [ 1073613-05-4 ]
YieldReaction ConditionsOperation in experiment
92% With copper(ll) sulfate pentahydrate; sodium L-ascorbate In water; <i>tert</i>-butyl alcohol at 20℃; for 24h;
92% In water; <i>tert</i>-butyl alcohol at 20℃; for 24h; 7 Example 7; Synthesis of the tetrazolo group was performed essentially as described (see, e.g., Rostovtsev et al., Angew. Chem., Int. Ed. 41:2596-2599 (2002)). 1-Ethynyl-3-(trifluoromethyl)-benzen (0.85 g, 5 mmol) and 4-azidobenzoic acid (0.815 g, 5 mmol) were suspended in a 1:1 mixture of water and tert-butyl alcohol (10 mL). Freshly prepared solution of sodium ascorbate (0.3 mmol, 300 μL of 1 M) was added, followed by copper(II) sulfate pentahydrate (7.5 mg, 0.03 mmol, in 100 μL, of water). The mixture was stirred for 24 hr at room temperature until analysis by LC/MS indicated completion of reaction. The reaction mixture was diluted with water, white precipitate collected by filtration, washed and dried. After washing the precipitate with cold water (2×25 mL), the precipitate was dried under vacuum to afford 1.53 g (92%) of pure product as an off-white powder.
Reference： [1]Location in patent: experimental part Sonawane; Verkman [Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 17, p. 8187 - 8195]
[2]Current Patent Assignee: UNIVERSITY OF CALIFORNIA - US2011/105565, 2011, A1 Location in patent: Page/Page column 29
  • 27
  • [ 705-28-2 ]
  • [ 42340-98-7 ]
  • [ 1095393-72-8 ]
YieldReaction ConditionsOperation in experiment
89.2% Stage #1: 1-ethynyl-3-trifluoromethylbenzene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: (R)-1-(1-naphthyl)ethyl isocyanate In tetrahydrofuran; hexane at -78℃; for 0.5h; 4 Example 4 - Alkvne Reduction; [0128] The invention also provides, in another embodiment, an alternative route for synthesizing cinacalcet via the reduction of an alkyne precursor. The precursor is obtained by reacting an aryl acetylene with an appropriately substituted isocyanate. For example, a solution of 3-ethvnyl-α,α,α-trifluorotoluene (0.73mL; 5.06mmol; 2.0 equiv.) in anhydrous THF (20 mL) was cooled to -78°C (acetone/dry ice bath). A hexane solution of n-BuLi (1.6M, 2.69mL; 4.30 mmol; 1.7 equiv.).is then added and the reaction mixture stirred at - 78°C for 30 minutes. A solution of (R)-l-(l-isocyanatoethyl)naphthalene (1.0 equiv.; 2.53 mmol ; 0.447mL) in THF is then added to the reaction mixture which is stirred for an additional 30 minutes at -78°C. The reaction is stopped by the addition of an aqueous solution of ammonium chloride to the organic mixture. The organic layer is repeatedly extracted with water, dried over magnesium sulfate and the solvent removed in vacuo to afford 3-(3-Trifluoromethyl-phenyl)-propynoic acid ((R)-l-naphthalen-l-yl-ethyl)-amide as product. Isolated 830mg, 89.2% yield. The identity of the product is confirmed by 1H NMR and high resolution mass spectrometry. (300MHz, CDCl3) δ ppm 1.77 (d, 3H) 5.97-6.08 (m, IH) 6.15 (br. S., IH) 7.42-7.70 (m, 7H) 7.75 (s, IH) 7.81-7.94 (m, 2H) 8.12 (d, IH) and HRMS (M+l): 368.1
Reference： [1]Current Patent Assignee: AMGEN INC - WO2009/2427, 2008, A2 Location in patent: Page/Page column 41
  • 28
  • [ 705-28-2 ]
  • [ 6630-33-7 ]
  • [ 1173882-91-1 ]
YieldReaction ConditionsOperation in experiment
89% Stage #1: 1-ethynyl-3-trifluoromethylbenzene; ortho-bromobenzaldehyde With trans-bis(triphenylphosphine)palladium dichloride; triethylamine at 20℃; for 0.166667h; Inert atmosphere; Stage #2: With copper(l) iodide at 50℃; for 6h; Inert atmosphere;
74% With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 50℃; for 6h; Inert atmosphere;
74% Stage #1: 1-ethynyl-3-trifluoromethylbenzene; ortho-bromobenzaldehyde With bis-triphenylphosphine-palladium(II) chloride; triethylamine at 20℃; for 0.25h; Inert atmosphere; Stage #2: With copper(l) iodide at 50℃; for 6h; Inert atmosphere;
Stage #1: 1-ethynyl-3-trifluoromethylbenzene; ortho-bromobenzaldehyde With bis-triphenylphosphine-palladium(II) chloride; triethylamine for 0.0833333h; Stage #2: With copper(l) iodide at 50℃; for 4h; Inert atmosphere;
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 50℃; for 4h; Inert atmosphere;

Reference： [1]Dell'Acqua, Monica; Pirovano, Valentina; Peroni, Stefano; Tseberlidis, Giorgio; Nava, Donatella; Rossi, Elisabetta; Abbiati, Giorgio [European Journal of Organic Chemistry, 2017, vol. 2017, # 11, p. 1425 - 1433]
[2]Location in patent: experimental part Alfonsi, Maria; Dell'Acqua, Monica; Facoetti, Diego; Arcadi, Antonio; Abbiati, Giorgio; Rossi, Elisabetta [European Journal of Organic Chemistry, 2009, # 17, p. 2852 - 2862]
[3]Location in patent: experimental part Dell'Acqua, Monica; Facoetti, Diego; Abbiati, Giorgio; Rossi, Elisabetta [Synthesis, 2010, # 14, p. 2367 - 2378]
[4]Jeganathan, Mariappan; Pitchumani, Kasi [RSC Advances, 2014, vol. 4, # 73, p. 38491 - 38497]
[5]Jeganathan, Mariappan; Pitchumani, Kasi [RSC Advances, 2014, vol. 40, # 73, p. 38491 - 38497]
  • 29
  • [ 705-28-2 ]
  • [ 14337-43-0 ]
  • [ 871676-36-7 ]
YieldReaction ConditionsOperation in experiment
With triethylamine In tetrahydrofuran at 20℃; Cooling with ice; 1.E.1 Step 1 - Preparation of a Compound of Formula (k)[0161] To a stirred solution of ethyl chlorooximidoacetate (6.68 g, 44.09 mmol) in tetrahydrofuran (90 mL) in an ice bath was added 3-(trifluoromethyl)phenylacetylene (5.0 g, 29.39 mmol) slowly, followed by triethylamine (8.19 mL, 58.78 mmol) dropwise. The resulting mixture was stirred at room temperature overnight, which was then filtered through a layer of silica gel (top) and anhydrous Na2SO4 (bottom), and washed with ethyl acetate. The filtrate was washed with water, the organic layer dried over sodium sulfate, and the solvent removed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:Hexanes = 1 : 9) to afford ethyl 5-[3-(trifluoromethyl)phenyl]isoxazole-3-carboxylate.
Reference： [1]Current Patent Assignee: GILEAD SCIENCES INC; THE ENDOWMENT FOR RESEARCH IN HUMAN BIOLOGY INC - WO2009/94028, 2009, A1 Location in patent: Page/Page column 55
  • 30
  • [ 880263-69-4 ]
  • [ 705-28-2 ]
  • [ 1196468-56-0 ]
YieldReaction ConditionsOperation in experiment
92% With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine In N,N-dimethyl-formamide at 20℃; Inert atmosphere;
Reference： [1]Location in patent: body text Facoetti, Diego; Abbiati, Giorgio; D'Avolio, Laura; Ackermann, Lutz; Rossi, Elisabetta [Synlett, 2009, # 14, p. 2273 - 2276]
  • 31
  • [ 705-28-2 ]
  • [ 704911-41-1 ]
  • [ 1123187-54-1 ]
YieldReaction ConditionsOperation in experiment
71% With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine In acetonitrile at 100℃; for 0.5h; Microwave irradiation; Inert atmosphere;
Reference： [1]Location in patent: experimental part Wan, Jinqiao; Xia, Yi; Liu, Yang; Wang, Menghua; Rocchi, Palma; Yao, Jianhua; Qu, Fanqi; Neyts, Johan; Iovanna, Juan L.; Peng, Ling [Journal of Medicinal Chemistry, 2009, vol. 52, # 4, p. 1144 - 1155]
  • 32
  • [ 705-28-2 ]
  • 3-bromo-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-1,2,4-triazole-5-carboxylic acid methyl ester [ No CAS ]
  • [ 1106736-14-4 ]
YieldReaction ConditionsOperation in experiment
64% With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine In acetonitrile at 100℃; for 0.5h; Inert atmosphere; Microwave irradiation;
Reference： [1]Location in patent: experimental part Xia, Yi; Liu, Yang; Wan, Jinqiao; Wang, Menghua; Rocchi, Palma; Qu, Fanqi; Iovanna, Juan L.; Peng, Ling [Journal of Medicinal Chemistry, 2009, vol. 52, # 19, p. 6083 - 6096]
  • 33
  • [ 533-58-4 ]
  • [ 705-28-2 ]
  • 2-(3’-trifluoromethylphenyl)benzofuran [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With potassium carbonate; triphenylphosphine at 60℃; for 4h; 2-Phenylbenzofuran (1a); Typical Procedure General procedure: A freshly prepared solution of PdNPs (12.5 mL) was taken up in a 25-mL round-bottomed flask. To this solution K2CO3 (0.276 g, 2 mmol)and Ph3P (0.052 g, 0.2 mmol) were added followed by 2-iodophenol(0.22 g, 1 mmol) and phenylacetylene (0.122 g, 1.2 mmol). Then, themixture was stirred at 60 °C under aerobic conditions. The reactionwas monitored by TLC until complete consumption of phenylacetylene.When the reaction was complete, the solvents were evaporatedand the residue was purified by column chromatography (hexane-EtOAc). Yields for all compounds are calculated after column chromatography.The catalyst could be recycled. The size of the PdNPs afterfour catalytic cycles was found in the range of 12-18 nm by TEM analysisindicating some agglomeration.The reactions of 2-iodophenol or methyl 4-hydroxy-3-iodobenzoatewith arylacetylenes were carried out as given in the typical procedure.However, reactions using alkylacetylenes did not require theuse of Ph3P.
60% With rac-N2,N2'-bis(benzyl)-1,1'-binaphthyl-2,2'-diamine; copper(II) bis(trifluoromethanesulfonate); potassium carbonate In toluene for 24h; Inert atmosphere; Reflux;
Reference： [1]Mandali, Pavan Kumar; Chand, Dillip Kumar [Synthesis, 2015, vol. 47, # 11, p. 1661 - 1668]
[2]Location in patent: experimental part Jaseer; Prasad; Sekar, Govindasamy [Tetrahedron, 2010, vol. 66, # 11, p. 2077 - 2082]
  • 34
  • [ 1229567-38-7 ]
  • [ 705-28-2 ]
  • C21H19F3N2O2 [ No CAS ]
  • C21H19F3N2O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% In ethanol at 80℃; for 18h;
Reference： [1]Dai, Xing; Miller, Michael W.; Stamford, Andrew W. [Organic Letters, 2010, vol. 12, # 12, p. 2718 - 2721]
  • 35
  • [ 705-28-2 ]
  • [ 13073-26-2 ]
  • C15H8F3NO3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With piperidine; bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide In N,N-dimethyl-formamide at 60℃; Inert atmosphere;
Reference： [1]Location in patent: scheme or table Thalji, Reema K.; Aiyar, Nambi; Davenport, Elizabeth A.; Erhardt, Joseph A.; Kallal, Lorena A.; Morrow, Dwight M.; Senadhi, Shobha; Burns-Kurtis, Cynthia L.; Marino Jr., Joseph P. [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 14, p. 4104 - 4107]
  • 36
  • [ 934281-60-4 ]
  • [ 705-28-2 ]
  • [ 1254971-24-8 ]
YieldReaction ConditionsOperation in experiment
72% With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); lithium carbonate In 1,4-dioxane; water at 100℃; for 0.416667h; Inert atmosphere; Microwave irradiation;
Reference： [1]Wang, Menghua; Xia, Yi; Fan, Yuting; Rocchi, Palma; Qu, Fanqi; Iovanna, Juan L.; Peng, Ling [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 20, p. 5979 - 5983]
  • 37
  • [ 705-28-2 ]
  • [ 1258527-91-1 ]
  • [ 1258527-84-2 ]
YieldReaction ConditionsOperation in experiment
48% With sodium 2-(1,2-dihydroxyethyl)-4-hydroxy-5-oxo-2,5-dihydro-furan-3-olate In water; N,N-dimethyl-formamide at 20℃; 2 Step 2 To a stirred solution of 7a (104.5 mg, 0.206 mmol) in DMF (1 mL) was added alkyne (19.6 μl_, 0.206 mmol) at room temperature. 1 M Sodium ascorbate solution in water (41.2 μl_, 0.0412 mmol) was added, followed by the addition of 1 M CuSO4-5H2O solution (20.6 μl_, 0.0206 mmol). The heterogeneous mixture was stirred vigorously at room temperature overnight, at which point it cleared, and TLC analysis indicated reaction completion. The resulting reaction mixture was diluted with H2O, treated with two drops of 30% H2O2 solution (aq) and 1 mL of saturated EDTA (aq). The aqueous layer was extracted with CH2CI2 (50 mL x2). The combined organic layer was washed with H2O, dried over MgSO4, filtered, and concentrated. The resulting crude product was purified by column chromatography to afford 67 mg (48 %) of the title compound 7-1 . MH+ 676
Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2010/147947, 2010, A2 Location in patent: Page/Page column 194-195
  • 38
  • [ 67-56-1 ]
  • [ 705-28-2 ]
  • [ 6630-33-7 ]
  • [ 1246365-05-8 ]
YieldReaction ConditionsOperation in experiment
88% Stage #1: methanol; 1-ethynyl-3-trifluoromethylbenzene; ortho-bromobenzaldehyde With bis-triphenylphosphine-palladium(II) chloride; potassium <i>tert</i>-butylate at 20℃; for 0.166667h; Inert atmosphere; Stage #2: With copper(l) iodide at 80℃; for 2h; Inert atmosphere; Sealed vessel; Microwave irradiation; 4.2. Representative procedure for the synthesis of compounds 3 General procedure: In a 12 mL MW glass vessel, a mixture of the appropriate 2-bromoarylaldehyde 1 (1 mmol), alkyne (1.2 mmol), t-BuOK (337 mg, 3 mmol), and PdCl2(PPh3)2 (14.0 mg, 0.02 mmol) in dry methanol (4 mL) was stirred at room temperature under a nitrogen atmosphere for 10 min, then CuI (3.81 mg, 0.02 mmol) was added. The reactor vessel was sealed and the stirred mixture was heated at the suitable temperature for the proper time in a multimode microwave oven (for times and temperatures see Table 2). After cooling, the reaction mixture was poured into NaHCO3 satd soln (20 mL) and extracted with ethyl acetate (3×10 mL). The organic layer, dried over Na2SO4, was evaporated under reduced pressure. The reaction crude was purified by flash column chromatography on SiO2 (40-63 μm). Compounds 3a-c, e are known.9
Reference： [1]Dell'Acqua, Monica; Facoetti, Diego; Abbiati, Giorgio; Rossi, Elisabetta [Tetrahedron, 2011, vol. 67, # 8, p. 1552 - 1556]
  • 39
  • [ 705-28-2 ]
  • [ 73183-34-3 ]
  • [ 1073354-88-7 ]
YieldReaction ConditionsOperation in experiment
78% Stage #1: bis(pinacol)diborane With [1,3-bis(1-adamantyl)imidazolidin-2-yl]chloro-copper; sodium t-butanolate In tetrahydrofuran at 22℃; for 0.5h; Inert atmosphere; Stage #2: 1-ethynyl-3-trifluoromethylbenzene With methanol In tetrahydrofuran at 22℃; for 12h; Inert atmosphere; regioselective reaction;
Reference： [1]Jang, Hwanjong; Zhugralin, Adil R.; Lee, Yunmi; Hoveyda, Amir H. [Journal of the American Chemical Society, 2011, vol. 133, # 20, p. 7859 - 7871]
  • 40
  • [ 705-28-2 ]
  • [ 73183-34-3 ]
  • 2-phenylvinylboronic acid [ No CAS ]
  • 4,4,5,5-tetramethyl-2-(1-(3-(trifluoromethyl)phenyl)ethenyl)-1,3,2-dioxaborolane [ No CAS ]
YieldReaction ConditionsOperation in experiment
86% Stage #1: bis(pinacol)diborane With C29H39ClCuN; sodium t-butanolate In tetrahydrofuran at 22℃; for 0.0833333h; Inert atmosphere; Stage #2: 1-ethynyl-3-trifluoromethylbenzene In tetrahydrofuran; methanol at 22℃; for 12h; Inert atmosphere;
52% With methanol; (1,3-bis(2,6-di-iso-propylphenyl)-4,5-dihydroimidazol-2-ylidene) copper chloride; sodium t-butanolate In tetrahydrofuran at -15℃; for 24h; Inert atmosphere; regioselective reaction;
Reference： [1]Bertrand, Guy; Engle, Keary M.; Gao, Yang; Grotjahn, Douglas B.; Jazzar, Rodolphe; Junor, Glen P.; Kang, Taeho; Kendrick, Aaron; Yazdani, Sima [Angewandte Chemie - International Edition, 2021, vol. 60, # 36, p. 19871 - 19878][Angew. Chem., 2021, vol. 133, # 36, p. 20024 - 20031]
[2]Location in patent: scheme or table Jang, Hwanjong; Zhugralin, Adil R.; Lee, Yunmi; Hoveyda, Amir H. [Journal of the American Chemical Society, 2011, vol. 133, # 20, p. 7859 - 7871]
  • 41
  • [ 705-28-2 ]
  • [ 166392-81-0 ]
  • [ 1313271-91-8 ]
YieldReaction ConditionsOperation in experiment
94% Stage #1: 1-ethynyl-3-trifluoromethylbenzene; methyl 3-tert-butyldimethylsilyloxy-2-diazobut-3-enoate With Rh2(S-PTAD)4 In dichloromethane at 0℃; for 2.5h; Inert atmosphere; Stage #2: With tetrabutyl ammonium fluoride In dichloromethane at 23℃; Inert atmosphere; optical yield given as %ee; enantioselective reaction; 4.3. General procedure for Rh(II)-catalyzed decompositions of siloxyvinyldiazoacetate 5 in the presence of acetylenes General procedure: A mixture of alkyne 6 (0.5 mmol) and Rh2(S-PTAD)4 (0.01 mmol) was dissolved in 1 mL of dichloromethane and stirred at -45 °C under an atmosphere of argon. Siloxyvinyldiazoacetate 5 (1.0 mmol) in 10 mL dichloromethane was then added to the reaction mixture via syringe pump over 2 h. After the complete addition, the reaction mixture was stirred for additional 20 min followed by addition of TBAF (1.0 mmol) in one portion. The reaction mixture was further stirred at 23 °C followed by aqueous work-up. The organic layer was dried over MgSO4, filtered, and concentrated. The residue was purified on silica using 10:1 hexane/diethyl ether followed by 1:1 hexane/EtOAc as eluents to afford the desired cyclopropenyl ketones.
Reference： [1]Location in patent: experimental part Briones, John F.; Davies, Huw M.L. [Tetrahedron, 2011, vol. 67, # 24, p. 4313 - 4317]
  • 42
  • [ 86-90-8 ]
  • [ 705-28-2 ]
  • [ 1260374-09-1 ]
Reference： [1]Polymer,2011,vol. 52,p. 138 - 148
  • 43
  • [ 705-28-2 ]
  • [ 73183-34-3 ]
  • [ 1073354-88-7 ]
  • 4,4,5,5-tetramethyl-2-(1-(3-(trifluoromethyl)phenyl)ethenyl)-1,3,2-dioxaborolane [ No CAS ]
YieldReaction ConditionsOperation in experiment
52% With NaOC(CH3)3; CH3OH In tetrahydrofuran 1.0 mol% Cu-complex, alkyne, diborane, NaOC(CH3)3, CH3OH, THF, -15°C, 24 h, N2 atm.; 89:11 ratio of isomers;
With C151H156ClCuN2O28; potassium <i>tert</i>-butylate In tetrahydrofuran; methanol at 20℃; for 16h; Inert atmosphere; regioselective reaction;
Reference： [1]Jang, Hwanjong; Zhugralin, Adil R.; Lee, Yunmi; Hoveyda, Amir H. [Journal of the American Chemical Society, 2011, vol. 133, # 20, p. 7859 - 7871]
[2]Zhang, Pinglu; Meijide Suárez, Jorge; Driant, Thomas; Derat, Etienne; Zhang, Yongmin; Ménand, Mickaël; Roland, Sylvain; Sollogoub, Matthieu [Angewandte Chemie - International Edition, 2017, vol. 56, # 36, p. 10821 - 10825][Angew. Chem., 2017, vol. 129, # 36, p. 10961 - 10965]
  • 44
  • [ 705-28-2 ]
  • [ 1329682-05-4 ]
  • [ 1329681-95-9 ]
YieldReaction ConditionsOperation in experiment
92% Stage #1: 1-ethynyl-3-trifluoromethylbenzene With copper(l) iodide; tris((1-(tert-butyl)-1H-1,2,3-triazol-4-yl)methyl)amine In dichloromethane at 20℃; for 0.0833333h; Stage #2: ethyl 5-azido-1-p-tolyl-1H-1,2,4-triazole-3-carboxylate In dichloromethane
Reference： [1]Zibinsky, Mikhail; Fokin, Valery V. [Organic Letters, 2011, vol. 13, # 18, p. 4870 - 4872]
  • 45
  • [ 705-28-2 ]
  • [ 84199-61-1 ]
  • [ 1350844-43-7 ]
Reference： [1]Organic and Biomolecular Chemistry,2011,vol. 9,p. 7836 - 7848
  • 46
  • [ 705-28-2 ]
  • [ 1345974-39-1 ]
  • [ 1345974-55-1 ]
YieldReaction ConditionsOperation in experiment
86% With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 110℃; for 0.166667h; Microwave irradiation;
Reference： [1]Location in patent: experimental part Bengtsson, Christoffer; Almqvist, Fredrik [Journal of Organic Chemistry, 2011, vol. 76, # 23, p. 9817 - 9825]
  • 47
  • [ 705-28-2 ]
  • [ 1380594-88-6 ]
  • [ 1380594-95-5 ]
YieldReaction ConditionsOperation in experiment
89% With copper(I) sulfate; sodium L-ascorbate; tris[(1-benzyl-1H-1,2,3-triazol-4yl)methyl]amine In ethanol; water at 20℃;
Reference： [1]Location in patent: experimental part Wang, Chao; Xie, Fang; Suthiwangcharoen, Nisaraporn; Sun, Jian; Wang, Qian [Science China Chemistry, 2012, vol. 55, # 1, p. 125 - 130]
  • 48
  • [ 705-28-2 ]
  • [ 622-79-7 ]
  • [ 1370006-17-9 ]
YieldReaction ConditionsOperation in experiment
97% With copper(ll) sulfate pentahydrate; betaine; sodium L-ascorbate In water at 30℃; for 24h;
96% With copper(ll) sulfate pentahydrate; sodium L-ascorbate; β‐cyclodextrin In water at 20℃; for 0.116667h;
Reference： [1]Shin, Jung-Ah; Oh, Su-Jin; Lee, Hee-Yoon; Lim, Yeong-Gweon [Catalysis science and technology, 2017, vol. 7, # 12, p. 2450 - 2456]
[2]Location in patent: experimental part Shin, Jung-Ah; Lim, Yeong-Gweon; Lee, Kyung-Hee [Journal of Organic Chemistry, 2012, vol. 77, # 8, p. 4117 - 4122]
  • 49
  • [ 705-28-2 ]
  • [ 119707-89-0 ]
  • [ 1380498-42-9 ]
YieldReaction ConditionsOperation in experiment
100% With sodium L-ascorbate In water; dimethyl sulfoxide at 65℃; for 2.5h; Inert atmosphere; 31 General synthesis procedure of 8-(lH-l,2,3-triazol-l-yl)-lH-purine-2,6(3H,7H)-dione derivatives 25 6 2 wherein X and Y are defined as above.[218] In a 50 mL round bottom flask with magnetic stirrer and reflux condenser, 19.0 mg (0.10 mmol, 0.20 eq.) copper (I) iodide, 19.8 mg (0.10 mmol, 0.20 eq.) (+)-sodium L-ascorbate and (0.50 mmol, 1.0 eq.) 8-azido-lH-purine-2,6(3H,7H)-dione derivative 5 were suspended in 5.0 mL dimethyl sulfoxide and 1.0 mL water. Then, (0.76-1.62 mmol, 1.5-3.2 eq.) alkyne of general formula 6 and Ι .Ο μΙ. (0.15 mmol, 0.30 eq.) Ν,Ν'-dimethylethylenediamine were added and heated at 65 °C under argon atmosphere for 2.5 h. Then, the mixture was cooled to room temperature and water and diluted hydrochloric acid were added. The precipitate was filtered off and washed with water. The solid was dried at 50-75 °C in a drying oven.; Example 31 : l,3-Dimethyl-8-(4-(3-(trifluoromethyl)phenyl)-lH-l,2,3-triazol-l-yl)-lH- purine-2,6(3H,7H)-dione (2a) [220] Reaction conditions: According to the general synthesis procedure 0.11 g (0.50 mmol, 1.0 eq.) 8-azido-l,3-dimethyl-lH-purine-2,6(3H,7H)-dione (5a) and 0.15 g (0.87 mmol, 1.7 eq.) l-ethynyl-3-(trifluoromethyl)benzene (6a) were used. The product 2a was isolated as a light yellow solid in 100 % yield (0.20 g).Analytical data: mp 294 °C. TLC: Rf = 0.41 (silica gel, dichloromethane/methanol 9 : 1). LC-MS (m/z): 364.1 [M-N2+H]+ + 392.5 [M+H]+ + 414.1 [M+Na]+ + 347.1 [M-N2-CH3-H]- + 362.3 [M-N2-H]- + 390.1 [M-H]-. Purity by HPLC-UV (254 nm)-ESI-MS: 99 %. 1H-NMR (500 MHz, DMSO): δ = 3.24 (s; 3H), 3.46 (s; 3H), 7.70-7.71 (m; 2H), 8.28-8.29 (m; 1H), 8.33 (s; 1H). 13C-NMR (126 MHz, DMSO): δ = 27.5, 30.0, 114.4, 121.6 (3JC,F = 3.7 Hz), 121.6 (3JC,F = 3.7 Hz), 123.1 (1JC.F = 272.2 Hz), 124.2 (3JC,F = 3.6 Hz), 124.3 (3JC,F = 3.6 Hz), 125.2 (1JC,F = 272.2 Hz), 129.1, 129.6 (2JC,F = 31.8 Hz), 129.9 (2JC,F = 31.8 Hz), 130.0, 131.7, 144.2, 147.6, 149.1, 151.7, 157.5.
Reference： [1]Current Patent Assignee: LIFE & BRAIN GMBH - WO2012/76974, 2012, A1 Location in patent: Page/Page column 62-64
  • 50
  • [ 705-28-2 ]
  • 2,5‐dimethoxybenzaldoxime [ No CAS ]
  • [ 1391056-61-3 ]
YieldReaction ConditionsOperation in experiment
84% With sodium hypochlorite; triethylamine In dichloromethane; water at 0 - 25℃; for 20h; Inert atmosphere; Typical experimental Procedure for the preparation of compound 9a: General procedure: To a solution of compound 8 (1 g, 5.52 mmol) in DCM (10 mL), phenyl acetylene (0.67 g, 6.62 mmol), TEA (0.83 g, 8.28 mmol), and sodium hypochlorite (9-12% in water) (10 ml) were added at 0 C under nitrogen atmosphere. Then the reaction mixture was stirred at rt 0 °C for 20 h. The progress of the reaction was monitored by TLC analysis (15% EA/pet ether). Then, water (50 ml) was added and the reaction mixture was extracted with DCM. The combined organic layer was washed with water followed by brine and dried over anhydrous Na2SO4. Evaporation of the solvent in high vacuum gave the compound 9a (1.32 g, 88% yield) as off white solid.
Reference： [1]Location in patent: experimental part Ravi Kumar; Behera, Manoranjan; Raghavulu; Jaya Shree; Yennam, Satyanarayana [Tetrahedron Letters, 2012, vol. 53, # 32, p. 4108 - 4113]
  • 51
  • [ 705-28-2 ]
  • [ 56413-96-8 ]
  • [ 1394156-87-6 ]
YieldReaction ConditionsOperation in experiment
70% With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); sodium carbonate In tetrahydrofuran at 80 - 85℃;
Reference： [1]Location in patent: scheme or table Ali, Hasrat; Van Lier, Johan E. [Tetrahedron Letters, 2012, vol. 53, # 36, p. 4824 - 4827]
  • 52
  • [ 705-28-2 ]
  • 1-[2-(methylsulfanyl)phenyl]diazonium tetrafluoroborate [ No CAS ]
  • [ 1276033-51-2 ]
YieldReaction ConditionsOperation in experiment
62% With eosin y In dimethyl sulfoxide at 20℃; for 14h; Irradiation;
Reference： [1]Hari, Durga Prasad; Hering, Thea; Koenig, Burkhard [Organic Letters, 2012, vol. 14, # 20, p. 5334 - 5337,4]
  • 53
  • [ 705-28-2 ]
  • [ 1421615-46-4 ]
  • [ 1421615-61-3 ]
YieldReaction ConditionsOperation in experiment
90% Stage #1: 1-ethynyl-3-trifluoromethylbenzene; (S)-tert-butyl [2,2,2-trifluoro-1-(2-iodophenyl)ethyl]carbamate With bis-triphenylphosphine-palladium(II) chloride; triethylamine In tetrahydrofuran at 20℃; for 0.166667h; Inert atmosphere; Stage #2: With copper(l) iodide In tetrahydrofuran for 6h; Inert atmosphere; Heating;
Reference： [1]Fustero, Santos; Ibáñez, Ignacio; Barrio, Pablo; Maestro, Miguel A.; Catalán, Silvia [Organic Letters, 2013, vol. 15, # 4, p. 832 - 835]
  • 54
  • [ 1143579-84-3 ]
  • [ 705-28-2 ]
  • [ 1421261-12-2 ]
YieldReaction ConditionsOperation in experiment
65% With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 20 - 40℃; Inert atmosphere;
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 40℃;
Reference： [1]He, Yantao; Xu, Jie; Yu, Zhi-Hong; Gunawan, Andrea M.; Wu, Li; Wang, Lina; Zhang, Zhong-Yin [Journal of Medicinal Chemistry, 2013, vol. 56, # 3, p. 832 - 842]
[2]He, Yantao; Liu, Sijiu; Menon, Ambili; Stanford, Stephanie; Oppong, Emmanuel; Gunawan, Andrea M.; Wu, Li; Wu, Dennis J.; Barrios, Amy M.; Bottini, Nunzio; Cato, Andrew C. B.; Zhang, Zhong-Yin [Journal of Medicinal Chemistry, 2013, vol. 56, # 12, p. 4990 - 5008]
  • 55
  • [ 705-28-2 ]
  • [ 73183-34-3 ]
  • 4,4,5,5-tetramethyl-2-(1-(3-(trifluoromethyl)phenyl)ethenyl)-1,3,2-dioxaborolane [ No CAS ]
YieldReaction ConditionsOperation in experiment
26% Stage #1: bis(pinacol)diborane With (1,3-bis(2,6-diisopropylphenyl)-2,3-dihydro-1H-imidazol-2-yl)copper(II) chloride; sodium t-butanolate In tetrahydrofuran at 20 - 25℃; for 0.666667h; Inert atmosphere; Stage #2: 1-ethynyl-3-trifluoromethylbenzene In tetrahydrofuran; methanol at -78 - 25℃; 4,4,5,5-Tetramethyl-2-(l-(3-(trifluoromethyl)phenyl)ethenyl)-l,3,2-dioxaborolane was prepared as follows: A flask was charged with (l ,3-bis(2,6-diisopropylphenyl)-2,3-dihydro-lH-imidazol-2- yl)copper(II) chloride (0.675 g, 1.38 mmol), sodium terr-butoxide (0.133 g, 1.38 mmol) and THF ( 100 ml) and stirred under nitrogen for 10 minutes. Bis(pinacolato)diborane (7.72 g, 30.4 mmol) was added to the solution and the mixture was stirred at room temperature for 30 minutes. The mixture was cooled to -78°C and a solution of 1- ethynyl-3-(trifluoromethyl)benzene (4.7 g, 27.6 mmol) in THF (20 ml) and MeOH (1.23 ml, 30.4 mmol) were added via syringe. The flask was then stirred at -40°C (Acetonitrile/CC>2 bath) overnight. Reaction was at room temperature in the morning. The reaction was cooled to -78°C and then filtered through a pad of silica and diatomaceous earth (sold under the trade mark "Celite") to give a brown solution which was concentrated and the residue was purified by silica chromatography eluting with 0- 5% Et20/Petrol to yield 4,4,5,5-tetramethyl-2-( 1 -(3-(trifluoromethyl)phenyI)ethenyl 1,3,2-dioxaborolane (2.15g, 26%) Ή NMR (400 MHz, Chloroform-d) δ 7.74 (s, 1H), 7.63 - 7.70 (m, 1 H), 7.48 - 7.53 (m, 1H), 7.40 - 7.47 (m, 1 H), 6.09 - 6.20 (m, 2H), 1.34 (s, 12H)
26% Stage #1: bis(pinacol)diborane With chloro[1,3-bis(2,6-di-i-propylphenyl)imidazol-2-ylidene]copper(I); sodium t-butanolate In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Stage #2: 1-ethynyl-3-trifluoromethylbenzene In tetrahydrofuran; methanol at -78 - 20℃; 4,4,5,5-Tetramethyl-2-(1-(3-(trifluoromethyl)phenyl)ethenyl)-1,3,2-dioxaborolane was prepared as follows:[0380]A flask was charged with (1,3-bis(2,6-diisopropylphenyl)-2,3-dihydro-1H-imidazol-2-yl)copper(II) chloride (0.675 g, 1.38 mmol), sodium tert-butoxide (0.133 g, 1.38 mmol) and THF (100 ml) and stirred under nitrogen for 10 minutes. Bis(pinacolato)diborane (7.72 g, 30.4 mmol) was added to the solution and the mixture was stirred at room temperature for 30 minutes. The mixture was cooled to -78° C. and a solution of 1-ethynyl-3-(trifluoromethyl)benzene (4.7 g, 27.6 mmol) in THF (20 ml) and MeOH (1.23 ml, 30.4 mmol) were added via syringe. The flask was then stirred at -40° C. (Acetonitrile/CO2 bath) overnight. Reaction was at room temperature in the morning. The reaction was cooled to -78° C. and then filtered through a pad of silica and diatomaceous earth (sold under the trade mark “Celite”) to give a brown solution which was concentrated and the residue was purified by silica chromatography eluting with 0-5% Et2O/Petrol to yield 4,4,5,5-tetramethyl-2-(1-(3-(trifluoromethyl)phenyl)ethenyl)-1,3,2-dioxaborolane (2.15 g, 26%)[0381]1H NMR (400 MHz, Chloroform-d) δ 7.74 (s, 1H), 7.63-7.70 (m, 1H), 7.48-7.53 (m, 1H), 7.40-7.47 (m, 1H), 6.09-6.20 (m, 2H), 1.34 (s, 12H)
Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2013/27000, 2013, A1 Location in patent: Page/Page column 60
[2]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US2013/52281, 2013, A1 Location in patent: Paragraph 0379-0381
  • 56
  • [ 705-28-2 ]
  • [ 1430117-60-4 ]
  • [ 1430117-68-2 ]
YieldReaction ConditionsOperation in experiment
88% With copper(ll) sulfate pentahydrate; sodium ascorbate In water; <i>tert</i>-butyl alcohol at 20℃; for 12h; Inert atmosphere;
Reference： [1]Thuy, Tran Thi Thu; Cuong, Nguyen Manh; Toan, Tran Quoc; Thang, Ngo Ngoc; Tai, Bui Huu; Nhiem, Nguyen Xuan; Hong, Hye-Jin; Kim, Sohyun; Legoupy, Stephanie; Koh, Young Sang; Kim, Young Ho [Archives of Pharmacal Research, 2013, vol. 36, # 7, p. 832 - 839]
  • 57
  • [ 75-75-2 ]
  • [ 705-28-2 ]
  • [ 64-19-7 ]
  • [ 1023922-05-5 ]
  • [ 1476849-84-9 ]
YieldReaction ConditionsOperation in experiment
85% With 8-methylquinoline 1-oxide; [bis(trifluoromethanesulfonyl)imidate](triphenylphosphine)gold(I) at 20℃; for 8h; Keto Acetates 2a-y; General Procedure General procedure: A mixture of 8-methylquinoline 1-oxide (62.0 mg, 0.39 mmol), MsOH (32.4 mg, 0.33 mmol), and Ph3PAuNTf2 (11.4 mg, 0.015mmol) was added to a soln of the appropriate alkyne 1 (0.30 mmol) in AcOH (5 mL), and the mixture was stirred at r.t. until the reaction was complete (TLC). The mixture was then concentrated and the residue was purified by chromatography (silica gel, hexanes-EtOAc).
Reference： [1]Wu, Chao; Liang, Zhiwu; Yan, Dong; He, Weimin; Xiang, Jiannan [Synthesis, 2013, vol. 45, # 18, p. 2605 - 2611]
  • 58
  • [ 7170-36-7 ]
  • [ 705-28-2 ]
  • methyl 6-[1-oxo-3-[3-(trifluoromethyl)phenyl]-2-propyn-1-yl]pyridine-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
302 mg Stage #1: 6-(methoxycarbonyl)pyridine-2-carboxylic acid With thionyl chloride In toluene at 60℃; for 3h; Inert atmosphere; Stage #2: 1-ethynyl-3-trifluoromethylbenzene With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 20℃; for 2h; Inert atmosphere; 14-13 Methyl 6-[1-oxo-3-[3-(trifluoromethyl)phenyl]-2-propyn-1-yl]pyridine-2-carboxylate Methyl 6-[1-oxo-3-[3-(trifluoromethyl)phenyl]-2-propyn-1-yl]pyridine-2-carboxylate Thionyl chloride (8 mL) was added to a toluene (37 mL) solution of 2-carboxy-6-methoxycarbonylpyridine (2.0 g) at room temperature under an argon atmosphere, and then the mixture was stirred at 60°C for 3 hours. A colorless crystal obtained by evaporating the reaction mixture was dissolved in tetrahydrofuran (37 mL), then 3-(trifluoromethyl)phenylacetylene (1.9 mL), copper (I) iodide (64 mg), dichlorobis(triphenylphosphine)palladium (II) (78 mg), and triethylamine (1.9 mL) were added at room temperature, and then the mixture was stirred at room temperature for 2 hours. The reaction mixture was evaporated and then the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 4:1) to obtain a title compound as brown liquid (302 mg). 1H-NMR (400 MHz, CDCl3) δ4.08 (3H, s), 7.59 (1H, t, J = 7.9 Hz), 7.76 (1H, d, J = 7.9 Hz), 7.95 (1H, d, J = 7.9 Hz), 8.05-8.10 (2H, m), 8.33 (1H, dd, J = 7.9,1.2 Hz), 8.38 (1H, dd, J = 7.9, 1.2 Hz).
Reference： [1]Current Patent Assignee: KISSEI PHARMACEUTICAL COMPANY LIMITED; KYORIN HOLDINGS, INC. - EP2669285, 2013, A1 Location in patent: Paragraph 0315; 0316
  • 59
  • [ 1204770-89-7 ]
  • [ 705-28-2 ]
  • C29H19BrF3NO3S [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 50℃;
Reference： [1]Andersson, Emma K.; Bengtsson, Christoffer; Evans, Margery L.; Chorell, Erik; Sellstedt, Magnus; Lindgren, Anders E.G.; Hufnagel, David A.; Bhattacharya, Moumita; Tessier, Peter M.; Wittung-Stafshede, Pernilla; Almqvist, Fredrik; Chapman, Matthew R. [Chemistry and Biology, 2013, vol. 20, # 10, p. 1245 - 1254]
  • 60
  • [ 705-28-2 ]
  • [ 1416915-86-0 ]
  • [ 1571151-69-3 ]
YieldReaction ConditionsOperation in experiment
18% In N,N-dimethyl-formamide at 100℃; for 20h; Inert atmosphere; General Procedure for the Synthesis of 1,5-disubstituted 1,2,3-triazolyl derivatives. General procedure: A solution of 2 (1.0 equiv) and the appropriate alkyne (1.1 - 4.8 equiv) in dry DMF (0.5 mL per mmol of 2) (for compounds 4h and 4j (AG2-481 and 482) Cp*Ru(PPh3)2Cl (0.02 equiv) was added) was stirred at 100 °C under an argon atmosphere for 20 h. Solvent was evaporated.
Reference： [1]Grandane, Aiga; Tanc, Muhammet; Zalubovskis, Raivis; Supuran, Claudiu T. [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 5, p. 1256 - 1260]
  • 61
  • [ 941-55-9 ]
  • [ 705-28-2 ]
  • [ 1616973-21-7 ]
YieldReaction ConditionsOperation in experiment
40% Stage #1: 1-ethynyl-3-trifluoromethylbenzene With copper(I) thiophene-2-carboxylate In toluene Cooling with ice; Stage #2: 4-toluenesulfonyl azide In toluene at 20℃;
40% With copper(I) thiophene-2-carboxylate In toluene at 20℃; Cooling with ice;
40% With copper(I) thiophene-2-carboxylate In toluene at 20℃; Inert atmosphere; Cooling with ice;
With copper(I) thiophene-2-carboxylate In toluene Inert atmosphere; regioselective reaction;
With copper(I) thiophene-2-carboxylate In toluene at 0 - 20℃; Inert atmosphere;

Reference： [1]Ran, Rui-Qiao; He, Jun; Xiu, Shi-Dong; Wang, Kai-Bing; Li, Chuan-Ying [Organic Letters, 2014, vol. 16, # 14, p. 3704 - 3707]
[2]Ran, Rui-Qiao; Xiu, Shi-Dong; Li, Chuan-Ying [Organic Letters, 2014, vol. 16, # 24, p. 6394 - 6396]
[3]Shi, Yinping; Yu, Xing; Li, Chuan-Ying [European Journal of Organic Chemistry, 2015, vol. 2015, # 29, p. 6429 - 6433]
[4]Rajasekar, Shanmugam; Yadagiri, Dongari; Anbarasan, Pazhamalai [Chemistry - A European Journal, 2015, vol. 21, # 47, p. 17079 - 17084]
[5]Duan, Shengguo; Jablasone, Saygbechi T.; Li, Chuan-Ying; Xu, Ze-Feng; Ye, Zihang [Organic and Biomolecular Chemistry, 2021, vol. 19, # 26, p. 5758 - 5761]
  • 62
  • [ 705-28-2 ]
  • [ 1369391-46-7 ]
  • 1-[3β-(t-butyldiphenylsilyloxy)-androst-5-en-17β-yl]-3-(3-trifluoromethylphenyl)-2-propyn-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
59% Stage #1: 1-ethynyl-3-trifluoromethylbenzene With n-butyllithium In tetrahydrofuran; hexane at -40℃; for 1h; Stage #2: (3S,10R,13S,17S)-3-((tert-butyldiphenylsilyl)oxy)-N-methoxy-N,10,13-trimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-17-carboxamide In tetrahydrofuran; hexane at -40 - -10℃; 1 General procedures for the synthesis of the alkynylaryl pregnenolone derivatives 5a-i General procedure: Method B. To a solution of n-BuLi (1.6 M solution in hexanes) in anhydrous THF (0.33 M, 2 equiv) was added at -40 °C the appropriate alkyne (3 equiv) and the reaction was stirred at that temperature for 1 h. Subsequently a solution of the Weinreb amide 4 (1 equiv) in THF (0.055 M) was added and the temperature was allowed to rise to -10 °C over 3 h and the reaction was stirred at -10 °C until completion. The reaction was quenched with saturated NH4Cl solution (3 mL) and was diluted with diethyl ether. The organic phase was washed with brine, was dried over anhydrous Na2SO4 and the solvent was evaporated in vacuo. The residue was purified by flash column chromatography to afford the desired compounds 5f-i.
Reference： [1]Szalki, György; Pantzou, Athanasia; Prousis, Kyriakos C.; Mavrofrydi, Olga; Papazafiri, Panagiota; Calogeropoulou, Theodora [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 24, p. 6980 - 6988]
  • 63
  • [ 705-28-2 ]
  • [ 7654-06-0 ]
  • 2,4-diphenyl-3-((3-(trifluoromethyl)phenyl)ethynyl)-1H-pyrrole [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% With copper (I) acetate In 1,4-dioxane at 20℃; for 20h; Inert atmosphere; Schlenk technique;
Reference： [1]Li, Tengfei; Xin, Xiaoyi; Wang, Chunxiang; Wang, Dongping; Wu, Fan; Li, Xincheng; Wan, Boshun [Organic Letters, 2014, vol. 16, # 18, p. 4806 - 4809]
  • 64
  • [ 705-28-2 ]
  • methyl 2-((6-iodo-2,2-dimethyl-4-oxo-4H-benzo[d][1,3]dioxin-7-yl)oxy)hexanoate [ No CAS ]
  • C26H25F3O6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 12h; Schlenk technique; Inert atmosphere; 14 General procedures for the preparation of compounds 4a-r General procedure: A Schlenk flask was charged with methyl 2-((6-iodo-2,2-dimethyl-4-oxo-4H-benzo[d][1,3]dioxin-7-yl)oxy)hexanoate (1 mmol),Pd(PPh3)Cl2 (0.03 mmol), iPr2NEt (4 mmol), alkyne (1.5 mmol). TheDMF (4 mL) was added and the flask was evacuated and backfilledwith N2 three times. After stirring 12 h at room temperature, thereaction was then diluted with water, extracted with EtOAc,washed with water and brine. The combined ethyl acetate layerswere dried over anhydrous Na2SO4, filtered, concentrated to givecompounds 3a-r, which was directly used in the next step withoutfurther purification. To a suspension of 3a-r (0.5 mmol) in MeOH(3 mL) was added 10% LiOH (3 mL). The obtained mixturewas refluxed for 2 h, then poured into water, acidified with 3 MHCl aq and extracted with ethyl acetate. The organic layerswere washed with brine, dried over anhydrous Na2SO4, filtered,and concentrated under reduced pressure. The residue was purifiedby HPLC to furnish the corresponding products 4a-r.Protocol for the Prep-HPLC purification method: reverse phaseHPLC was carried out on Sunfire Prep C18 OBD column(30 150 mm, 5 lm). Solvent A: water with 0.1% trifluoroaceticacid: Solvent B: methanol with 0.1% trifluoroacetic acid.Gradient: After 5 min at the initial condition of 90% A and 10% B,solvent B was increased to 100% within 45 min, then maintainedat 100% B for 10 min. Flow rate was 50 mL/min, UV detector at254 nm.
Reference： [1]He, Yantao; Guo, Xing; Yu, Zhi-Hong; Wu, Li; Gunawan, Andrea M.; Zhang, Yan; Dixon, Jack E.; Zhang, Zhong-Yin [Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 12, p. 2798 - 2809]
  • 65
  • [ 705-28-2 ]
  • 2-((3-iodoimidazo[1,2-a]pyridin-2-yl)methyl)isoindoline-1,3-dione [ No CAS ]
  • 2-((3-((3-(trifluoromethyl)phenyl)ethynyl)imidazo[1,2-a]pyridin-2-yl)methyl)isoindoline-1,3-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
59% With tris-(dibenzylideneacetone)dipalladium(0); copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 20℃; for 16h; Inert atmosphere; 12.3 Step 3: Preparation of 2-((3-((3-(trifluoromethyl)phenyl) ethynyl)imidazo[1,2-a]pyridin-2-yl)methyl)isoindoline-1,3-dione Step 3: Preparation of 2-((3-((3-(trifluoromethyl)phenyl) ethynyl)imidazo[1,2-a]pyridin-2-yl)methyl)isoindoline-1,3-dione In a flask placed under an argon flow, 2.1 g (5.21 mmol) of 2-((3-iodoimidazo[1,2-a]pyridin-2-yl)methyl)isoindoline-1,3-dione were solubilised in 11 ml of dimethylformamide with magnetic stirring. To this solution, were added: 0.008 g (0.04 mmol) of copper iodide, 0.921 ml (6.25 mmol) of 3-trifluoromethylphenyl acetylene and 10.89 ml (78 mmol) of triethylamine. The reaction medium was degassed with argon for 10 min before adding 0.477 g (0.521 mmol) of Pd2(dba)3. The mixture was stirred at r.t. for 16 h before being filtered on a silica gel cartridge which was then rinsed with 300 ml of ethyl acetate. The organic phase was washed with 3*150 ml of a saturated NaCl aqueous solution, and then dried on Na2SO4 which was then removed by filtration. The obtained filtrate was concentrated in vacuo. The crude residue was purified by flash chromatography on a silica gel cartridge (eluent: heptane/ethyl acetate gradient, from 50% to 40% of heptane, v/v). 1.41 g (yield=59%) of 2-((3-((3-(trifluoromethyl)phenyl)ethynyl)imidazo[1,2-a]pyridin-2-yl)methyl) isoindoline-1,3-dione were obtained as a brown solid. LC-MS: m/z=446 (MH+); UV purity at 254 nm=97%. 1H NMR (300 MHz, DMSO) δ 8.67 (d, J=6.7 Hz, 1H), 7.91 (dd, J=5.6, 3.0 Hz, 2H), 7.82 (dd, J=5.5, 3.1 Hz, 2H), 7.69 (dd, J=12.5, 8.5 Hz, 2H), 7.63-7.52 (m, 2H), 7.52-7.42 (m, 2H), 7.13 (td, J=6.8, 1.1 Hz, 1H), 5.09 (s, 2H).
Reference： [1]Current Patent Assignee: METABRAIN RESEARCH - US2015/182507, 2015, A1 Location in patent: Paragraph 0176; 0177
  • 66
  • [ 705-28-2 ]
  • methyl 2-(((3-iodoimidazo[1,2-a]pyridin-2-yl)methyl)(methyl)amino)acetate [ No CAS ]
  • methyl 2-(methyl((3-((3-(trifluoromethyl)phenyl)ethynyl)imidazo[1,2-a]pyridin-2-yl)methyl)amino)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
57% With tris-(dibenzylideneacetone)dipalladium(0); copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 20℃; for 16h; Inert atmosphere; 14.3 Step 3: Preparation of methyl 2-(methyl((3-((3-(trifluoromethyl)phenyl)ethynyl)imidazo[1,2-a]pyridin-2-yl)methyl)amino)acetate (Derivative Number 72) Step 3: Preparation of methyl 2-(methyl((3-((3-(trifluoromethyl)phenyl)ethynyl)imidazo[1,2-a]pyridin-2-yl)methyl)amino)acetate (Derivative Number 72) In a flask placed under an argon flow, 0.093 g (0.212 mmol) of methyl 2-(((3-iodoimidazo[1,2-a]pyridin-2-yl)methyl)(methyl)amino)acetate were dissolved in 0.5 ml of dimethylformamide with magnetic stirring. To this solution, were added: 0.004 g (0.021 mmol) of copper iodide, 0.037 ml (0.255 mmol) of 3-trifluoromethylphenylacetylene and 0.444 ml (3.18 mmol) of triethylamine. The reaction medium was degassed with argon for 10 min before adding 0.019 g (0.021 mmol) of Pd2(dba)3. The mixture was stirred at r.t. for 16 h before being treated, diluted with 15 ml of ethyl acetate and washed with 2*15 ml of a saturated NaCl aqueous solution. The aqueous phase was extracted with 20 ml of ethyl acetate. The combined organic phases were dried on Na2SO4 which was then removed by filtration. The obtained filtrate was concentrated in vacuo. The crude residue was purified by flash chromatography on a silica gel cartridge (eluent: ethyl acetate 100%). 0.05 g (yield=57%) of methyl 2-(methyl((3-((3-(trifluoromethyl)phenyl)ethynyl)imidazo[1,2-a]pyridin-2-yl)methyl)amino)acetate were obtained as a pale brown solid. LC-MS: m/z=402 (MH+); UV purity at 254 nm=96%. 1H NMR (300 MHz, DMSO) δ 8.75 (d, J=6.7 Hz, 1H), 8.11 (s, 1H), 7.97 (d, J=7.6 Hz, 1H), 7.83-7.59 (m, 3H), 7.55-7.37 (m, 1H), 7.14 (td, J=6.8, 0.9 Hz, 1H), 3.97 (s, 2H), 3.58 (s, 3H), 3.43 (s, 2H), 2.39 (s, 3H).
Reference： [1]Current Patent Assignee: METABRAIN RESEARCH - US2015/182507, 2015, A1 Location in patent: Paragraph 0189; 0190
  • 67
  • [ 705-28-2 ]
  • ethyl 2-((6-chloro-3-iodoimidazo[1,2-a]pyridin-2-yl)methylthio)acetate [ No CAS ]
  • ethyl 2-[[6-chloro-3-[2-[3-(trifluoromethyl)phenyl]ethynyl]imidazo[1,2-a]pyridin-2-yl]methylsulfanyl]acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With tris-(dibenzylideneacetone)dipalladium(0); copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 20℃; for 1h; Inert atmosphere; 24.3 Step 3: Preparation of ethyl 2-((6-chloro-3-((3-(trifluoromethyl)phenyl)ethynyl)imidazo[1,2-a]pyridin-2-yl)methylthio)acetate Step 3: Preparation of ethyl 2-((6-chloro-3-((3-(trifluoromethyl)phenyl)ethynyl)imidazo[1,2-a]pyridin-2-yl)methylthio)acetate In an argon atmosphere, 27 g (59.8 mmol) of ethyl 2-((6-chloro-3-iodoimidazo[1,2-a]-pyridin-2-yl)methylthio)acetate, 9.51 ml (65.8 mmol) of 1-ethynyl-3-(trifluoromethyl)benzene, 1.139 g (5.98 mmol) of copper iodide and 125 ml (897 mmol) of triethylamine are loaded in 100 ml of DMF. Argon was bubbled in the solution for 10 min, and then 2.74 g (2.99 mmol) of Pd2(dba)3 were added. The mixture was stirred for 1 h at r.t. The catalyst was filtered on folded paper, the solution was poured onto 300 ml of water, extracted with 2*200 ml of ethyl acetate, the collected organic phases were washed with 3*150 ml of water and once with 150 ml of brine, dried on Na2SO4 which was then removed by filtration and the obtained filtrate was concentrated in vacuo. The residue was purified on a silica cake, and eluted with a heptane/ethyl acetate mixture. 23.21 g (yield=85%) of ethyl 2-((6-chloro-3-((3-(trifluoromethyl)phenyl)ethynyl)-imidazo[1,2-a]pyridin-2-yl)methylthio)acetate were obtained as a yellow solid. LC-MS: m/z=453 (MH+) UV purity at 254 nm=99%. 1H NMR (300 MHz, DMSO) δ 8.91 (dd, J=1.9, 0.6 Hz, 1H), 8.14 (s, 1H), 8.01 (d, J=7.6 Hz, 1H), 7.71 (ddd, J=14.3, 9.4, 4.3 Hz, 3H), 7.47 (dd, J=9.5, 2.0 Hz, 1H), 4.18-3.93 (m, 4H), 3.46 (s, 2H), 1.11 (t, J=7.1 Hz, 3H).
Reference： [1]Current Patent Assignee: METABRAIN RESEARCH - US2015/182507, 2015, A1 Location in patent: Paragraph 0234; 0235
  • 68
  • [ 705-28-2 ]
  • (((1R,4S)-4-(azidomethyl)cyclobut-2-enyl)methoxy)(tert-butyl)diphenylsilane [ No CAS ]
  • 1-(((1S,4R)-4-(((tert-butyldiphenylsilyl)oxy)methyl)cyclobut-2-enyl)methyl)-4-(3-(trifluoromethyl)phenyl)-1H-1,2,3-triazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
98% With copper(ll) sulfate pentahydrate; sodium L-ascorbate In water; <i>tert</i>-butyl alcohol at 20℃; for 12h; Inert atmosphere; General Procedure for the Azide-Alkyne Huisgen Cycloaddtion. General procedure: To a solution of azide 11 (0.3 g, 0.79 mmol) and selected alkyne (1.2 eq) in tBuOH (2 mL) were added sodium ascorbate 200 mol% (0.32 g, 1.58 mmol, in 1 mL H2O) and 20 mol% CuSO4.5H2O (40.5 mg, 0.16 mmol, in 1mL H2O) under argon atmosphere. The reaction mixture was stirred overnight at room temperature and then saturated NH4OH solution (5 mL) was added. The mixture was extracted with ethyl acetate (3 × 15 mL). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/EtOAc) to afford the 1,2,3-triazolocyclobutene.
Reference： [1]Tran, Thi Thu Thuy; Ngo, Ngoc Thang; Dinh, Thi Ha; Vo-Thanh, Giang; Legoupy, Stéphanie [Bulletin of the Korean Chemical Society, 2015, vol. 36, # 5, p. 1390 - 1395]
  • 69
  • [ 862730-04-9 ]
  • [ 705-28-2 ]
  • 1-isopropyl-3-((3-(trifluoromethyl)phenyl)ethynyl)-1H-pyrazolo-[3,4-d]pyrimidin-4-amine [ No CAS ]
Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 9228 - 9237
  • 70
  • [ 705-28-2 ]
  • 1-methoxy-1-(3-methoxyphenyl)isochroman [ No CAS ]
  • (S)-1-(3-methoxyphenyl)-1-((3-(trifluoromethyl)phenyl)ethynyl)isochroman [ No CAS ]
YieldReaction ConditionsOperation in experiment
96% Stage #1: 1-ethynyl-3-trifluoromethylbenzene; 1-methoxy-1-(3-methoxyphenyl)isochroman With copper(I) thiophenolate; 1-methyl-2,3,4,6,7,8-hexahydro-1H-pyrimido[1,2-a]pyrimidine; 2,6-bis[(4R)-5,5-dihydro-4-phenyl-2-oxazolyl]pyridine In chloroform at 0℃; for 0.166667h; Inert atmosphere; Glovebox; Sealed tube; Stage #2: With boron trifluoride diethyl etherate In chloroform at 4℃; for 48h; Sealed tube; enantioselective reaction;
Reference： [1]Dasgupta, Srimoyee; Rivas, Thomas; Watson, Mary P. [Angewandte Chemie - International Edition, 2015, vol. 54, # 47, p. 14154 - 14158][Angew. Chem.]
  • 71
  • [ 705-28-2 ]
  • methyl 5-azido-4'-(1-(2,2,2-trifluoroacetyl)piperidin-4-yl)-[1,1',-biphenyl]-3-carboxylate [ No CAS ]
  • methyl 5-(4-(3-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)-4'-(1-(2,2,2-trifluoroacetyl)piperidin-4-yl)-[1,1'-biphenyl]-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% With copper(II) sulfate; sodium L-ascorbate In tetrahydrofuran; water at 20℃; for 12h;
Reference： [1]Junker, Anna; Balasubramanian, Ramachandran; Ciancetta, Antonella; Uliassi, Elisa; Kiselev, Evgeny; Martiriggiano, Chiara; Trujillo, Kevin; Mtchedlidze, Giorgi; Birdwell, Leah; Brown, Kyle A.; Harden, T. Kendall; Jacobson, Kenneth A. [Journal of Medicinal Chemistry, 2016, vol. 59, # 13, p. 6149 - 6168]
  • 72
  • [ 201230-82-2 ]
  • [ 705-28-2 ]
  • [ 62-53-3 ]
  • 1-phenyl-3-(3-(trifluoromethyl)phenyl)pyrrolidine-2,5-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
93% With dichloro[4,5-bis(diphenylphosphino)-9,9’-dimethylxanthene]palladium(II); toluene-4-sulfonic acid In tetrahydrofuran at 125℃; for 8h; Autoclave;
Reference： [1]Liu, Huizhen; Lau, Genevieve P. S.; Dyson, Paul J. [Journal of Organic Chemistry, 2015, vol. 80, # 1, p. 386 - 391]
  • 73
  • [ 705-28-2 ]
  • 1-(1-azido-2-chloropropan-2-yl)-4-chlorobenzene [ No CAS ]
  • 1-(2-chloro-2-(4-chlorophenyl)propyl)-4-(3-(trifluoromethyl)phenyl)-1H-1,2,3-triazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
With copper In toluene; acetonitrile at 100℃; for 0.166667h; Flow reactor; GENERAL PROCEDURES FOR THE PREPARATION OF TRIAZOLES General procedure: (b) Flow procedureA 0.1 M solution of 1,2 azidochloride x in toluene (0.25 mL/min) and a 0.1 M solution of alkyne y inacetonitrile (0.25 mL/min) were combined at a T-piece and reacted at 100 °C in a 5 mL copper-coilreactor (Vapourtec, 1mm diameter) for a residence time of 10 minutes (a 8 bar back pressureregulator was used). The combined stream was collected and directly concentrated under reducedpressure. Purification, if necessary, was performed either by flash chromatography or by redissolvingthe crude micture in acetonitrile and provoking precipitation by the slow addition of water
Reference： [1]Leforestier, Baptiste; Vögtle, Markus [Synlett, 2016, vol. 27, # 13, p. 1957 - 1962]
  • 74
  • [ 705-28-2 ]
  • [ 814-49-3 ]
  • diethyl 2-(3-(trifluoromethyl)phenyl)ethynylphosphonate [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% Stage #1: 1-ethynyl-3-trifluoromethylbenzene With n-butyllithium In tetrahydrofuran at -78℃; for 2h; Inert atmosphere; Stage #2: diethyl chlorophosphate In tetrahydrofuran at -78 - 20℃; for 4h; Inert atmosphere;
Reference： [1]Manda, Sudhakar; Wani, Abubakar; Bharate, Sonali S.; Vishwakarma, Ram A.; Kumar, Ajay; Bharate, Sandip B. [MedChemComm, 2016, vol. 7, # 10, p. 1910 - 1915]
  • 75
  • [ 591-50-4 ]
  • [ 201230-82-2 ]
  • [ 705-28-2 ]
  • 1-phenyl-3-(3-(trifluoromethyl)phenyl)prop-2-yn-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% With C33H28Cl2N3PPd; triethylamine In toluene at 80℃; Schlenk technique;
Reference： [1]Dasgupta, Ayan; Ramkumar, Venkatachalam; Sankararaman, Sethuraman [European Journal of Organic Chemistry, 2016, vol. 2016, # 28, p. 4817 - 4823]
  • 76
  • [ 34244-15-0 ]
  • [ 201230-82-2 ]
  • [ 705-28-2 ]
  • 1-(pyren-1-yl)-3-(3-(trifluoromethyl)phenyl)prop-2-yn-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
57% With C33H28Cl2N3PPd; triethylamine In toluene at 80℃; Schlenk technique;
Reference： [1]Dasgupta, Ayan; Ramkumar, Venkatachalam; Sankararaman, Sethuraman [European Journal of Organic Chemistry, 2016, vol. 2016, # 28, p. 4817 - 4823]
  • 77
  • [ 124-38-9 ]
  • [ 705-28-2 ]
  • [ 402-24-4 ]
  • [ 1428555-36-5 ]
  • C19H10F6O2 [ No CAS ]
  • C18H10F6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 11% 2: 23% 3: 7% 4: 56% With [(bis(diisopropylphosphino)ethane)Ni(H)]2 In toluene at 50℃; for 69h; 4.2.1. General procedure for the catalytic production of aepyrones General procedure: [(dippe)Ni(m-H)]2 (1) (0.031 mmol) and the correspondingalkyne (0.311 mmol) and toluene (10 mL) were charged in a100-mL Parr reactor. On reacting 1 with all acetylenes, a colorchange from wine red to brown was observed with a lightbubbling; the reactor was immediately closed and then pressurizedout of the dry box with CO2 (150 psi). Afterward, thereaction vessel was heated up to 50 C for 69 h. After this time,the reactor was cooled down to room temperature and ventedinto a hood; the reaction mixture was directly analyzed by GCMS.
Reference： [1]Oliveros-Cruz, Saray; Arévalo, Alma; García, Juventino J. [Journal of Organometallic Chemistry, 2017, vol. 831, p. 18 - 22]
  • 78
  • [ 116393-71-6 ]
  • [ 705-28-2 ]
  • C15H9F3N2O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 20℃; General procedure for synthesis of 3: General procedure: To a solution of 2 (296 mg, 1.00 mmol) in THF (5 mL) at room temperature were added alkyne S4-6 (1.5 mmol), PdCl2(PPh3)2 (70.2 mg, 0.1 mmol), CuI (39.1 mg, 0.2 mmol), and Et3N (0.28 mL, 2 mmol). After being stirred at room temperature overnight, the reaction mixture was diluted with hexane, and then filtered. The residue was washed with CH2Cl2, and dried to give 3, which was used in the next reaction without further purification.
Reference： [1]Inaoka, Daniel Ken; Iida, Maiko; Honma, Teruki; Harada, Shigeharu; Nara, Takeshi; Balogun, Emmanuel Oluwadare; Kita, Kiyoshi; Hashimoto, Satoshi; Tanaka, Akiko; Kita, Kiyoshi; Tabuchi, Toshiyuki; Kuranaga, Takefumi; Inoue, Masayuki [Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 4, p. 1465 - 1470]
  • 79
  • [ 705-28-2 ]
  • [ 694-53-1 ]
  • (Z)-phenyl(3-(trifluoromethyl)styryl)silane [ No CAS ]
YieldReaction ConditionsOperation in experiment
86% With 2,6-bis[1-(2,4,6-trimethylimino)ethyl]pyridine; cobalt(II) acetate; phenol In tetrahydrofuran at 20℃; for 6h; Inert atmosphere; Glovebox; stereoselective reaction;
Reference： [1]Teo, Wei Jie; Wang, Chao; Tan, Ye Wei; Ge, Shaozhong [Angewandte Chemie - International Edition, 2017, vol. 56, # 15, p. 4328 - 4332][Angew. Chem., 2017, vol. 129, p. 4392 - 4396]
  • 80
  • [ 705-28-2 ]
  • [ 25015-63-8 ]
  • [ 1073354-88-7 ]
  • 4,4,5,5-tetramethyl-2-(1-(3-(trifluoromethyl)phenyl)ethenyl)-1,3,2-dioxaborolane [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 67 %Spectr. 2: 10 %Spectr. With platinum nanoparticles ligated by 1,3-bis[2,6-diisopropylphenyl]-4,5-diundecylimidazol-2-ylidene In hexane at 20℃; for 2h; Inert atmosphere; Schlenk technique;
Reference： [1]Martínez-Prieto, Luis M.; Rakers, Lena; López-Vinasco, Angela M.; Cano, Israel; Coppel, Yannick; Philippot, Karine; Glorius, Frank; Chaudret, Bruno; van Leeuwen, Piet W. N. M. [Chemistry - A European Journal, 2017, vol. 23, # 52, p. 12779 - 12786]
  • 81
  • [ 705-28-2 ]
  • 4-(4-azidophenoxy)-N-methylpicolinamide [ No CAS ]
  • N-methyl-4-(4-(4-(3-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)phenoxy)picolinamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
99% With sodium L-ascorbate In methanol at 25℃; for 16h; Inert atmosphere; Schlenk technique; 3.3. General Procedure for 2-Catalyzed 1,3-Dipolar Cycloaddition Reactions General procedure: Under N2 atmosphere, the mixture of alkyne (0.3 mmol), azide (0.3 mmol), Na ascorbate(0.006 mmol, 2 mol %), and 0.3 103 M solution of catalyst 2 in MeOH (0.1-0.3 mol %) was stirredin a 10 mL Schlenk tube at 25 °C for 16 h. Evaporation of the solvents followed by purification byshort column chromatography on silica gel provided the desired 1,4-disubstituted triazole product.The unreacted alkyne and azide were rst eluted out with 3/1 petroleum ether (PE)/ethyl acetate,and the pure 1,4-disubstituted triazole product was then obtained by elution with pure ethyl acetate.
Reference： [1]Ye, Wenjing; Yao, Qi; Yu, Simiao; Gong, Ping; Qin, Mingze [Molecules, 2017, vol. 22, # 10]
  • 82
  • [ 705-28-2 ]
  • methyl 4-(4-azidophenoxy)picolinate [ No CAS ]
  • methyl 4-(4-(4-(3-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)phenoxy)picolinate [ No CAS ]
YieldReaction ConditionsOperation in experiment
93% With sodium L-ascorbate In methanol at 25℃; for 16h; Inert atmosphere; Schlenk technique; 3.3. General Procedure for 2-Catalyzed 1,3-Dipolar Cycloaddition Reactions General procedure: Under N2 atmosphere, the mixture of alkyne (0.3 mmol), azide (0.3 mmol), Na ascorbate(0.006 mmol, 2 mol %), and 0.3 103 M solution of catalyst 2 in MeOH (0.1-0.3 mol %) was stirredin a 10 mL Schlenk tube at 25 °C for 16 h. Evaporation of the solvents followed by purification byshort column chromatography on silica gel provided the desired 1,4-disubstituted triazole product.The unreacted alkyne and azide were rst eluted out with 3/1 petroleum ether (PE)/ethyl acetate,and the pure 1,4-disubstituted triazole product was then obtained by elution with pure ethyl acetate.
Reference： [1]Ye, Wenjing; Yao, Qi; Yu, Simiao; Gong, Ping; Qin, Mingze [Molecules, 2017, vol. 22, # 10]
  • 83
  • [ 705-28-2 ]
  • [ 7438-05-3 ]
  • 1-octyl-4-(3-(trifluoromethyl)phenyl)-1H-1,2,3-triazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
94% With copper(ll) sulfate pentahydrate; betaine; sodium L-ascorbate In water at 30℃; for 24h;
Reference： [1]Shin, Jung-Ah; Oh, Su-Jin; Lee, Hee-Yoon; Lim, Yeong-Gweon [Catalysis science and technology, 2017, vol. 7, # 12, p. 2450 - 2456]
  • 84
  • [ 705-28-2 ]
  • [ 106-51-4 ]
  • 2-(3-(trifluoromethyl)phenyl)-3-((3-(trifluoromethyl)phenyl)ethynyl)benzofuran-5-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% With palladium diacetate In dimethyl sulfoxide at 100℃; for 12h; Inert atmosphere; Sealed tube;
Reference： [1]Ichake, Sachin S.; Konala, Ashok; Kavala, Veerababurao; Kuo, Chun-Wei; Yao, Ching-Fa [Organic Letters, 2017, vol. 19, # 1, p. 54 - 57]
  • 85
  • [ 705-28-2 ]
  • [ 1128277-93-9 ]
  • 1-(1-tert-butyl-3-nitro-azetidin-3-yl)-4-(3-trifluoromethyl-phenyl)-1H-1,2,3-triazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With copper(ll) sulfate pentahydrate; ascorbic acid In tetrahydrofuran; water at 20℃; for 4h; 4. General procedure for the synthesis of substituted 1H-1,2,3-triazoles (6c-k): General procedure: A solution of 3-azido-1-tert-butyl-3-nitro-azetidine 5 (995 mg, 5 mmol) and substituted acetylene (c-k) (5.25 mmol.) in THF (40 ml) was treated at room temperature by adding a solution of ascorbic acid (440 mg, 2.5 mmol) in water (20 ml), followed by a solution of CuSO4·5H2O (188 mg, 0.75 mmol) in water (10 ml). The reaction mixture was stirred for 2-6 h at room temperature. After the reaction was complete according to TLC, the mixture was diluted with water (20 ml) and extracted with CH2Cl2 (4×20 ml). The organic layer was dried over Na2SO4, the solvent was removed at reduced pressure, and the residue was purified by flash chromatography (EtOAc/n-hexane, 2:3) to give the desired products 6c-k as colorless solids.
Reference： [1]Dubovis, Mikhail V.; Rudakov, Gennady F.; Kulagin, Alexander S.; Tsarkova, Kseniya V.; Popkov, Sergey V.; Goloveshkin, Alexander S.; Cherkaev, Georgiy V. [Tetrahedron, 2018, vol. 74, # 6, p. 672 - 683]
  • 86
  • [ 705-28-2 ]
  • [ 349-76-8 ]
YieldReaction ConditionsOperation in experiment
72% With 4-methyl-morpholine; iodine In dimethyl sulfoxide at 120℃; for 16h; Synthesis of acetophenone derivatives (2a-q) General procedure: A 10 mL reaction flask was charged with terminal alkynes 1a-q (1.0 mmol), I2 (0.3 mmol) and N-methyl morpholine (1.0 mmol) in DMSO (2.0 mL) and then the reaction mixture was heated at 120 °C for 16 h. After completion of the reaction (progress was monitored by TLC; SiO2, hexane/EtOAc = 9:1), the recation mixture was quenched with saturated sodium thiosulphate solution, diluted with water (20 mL) and extracted with ethyl acetate (3 × 15 mL). The combined organic layer was dried over anhydrous Na2SO4. Solvent was removed under reduced pressure and the remaining residue was purified over silica gel column chromatography using hexane/EtOAc = 4:1 as an eluent to obtain the desired products 2a-q in high yields.
72% With 4-methyl-morpholine; iodine; dimethyl sulfoxide at 120℃; for 16h; Synthesis of acetophenone derivatives (2a-q) General procedure: A 10 mL reaction flask was charged with terminal alkynes 1a-q (1.0 mmol), I2 (0.3 mmol) and N-methyl morpholine (1.0 mmol) in DMSO (2.0 mL) and then the reaction mixture was heated at 120 °C for 16 h. After completion of the reaction (progress was monitored by TLC; SiO2, hexane/EtOAc = 9:1), the recation mixture was quenched with saturated sodium thiosulphate solution, diluted with water (20 mL) and extracted with ethyl acetate (3 × 15 mL). The combined organic layer was dried over anhydrous Na2SO4. Solvent was removed under reduced pressure and the remaining residue was purified over silica gel column chromatography using hexane/EtOAc = 4:1 as an eluent to obtain the desired products 2a-q in high yields.
57 %Chromat. With gold(III) trichloride; lithium hydroxide monohydrate In isopropanol at 65℃; for 24h;
Reference： [1]Anupam, R. O. Y.; Devi, Elangbam Pinky; Kaldhi, Dhananjaya; Malakar, Chandi C.; Saha, Indranil; Sahoo, Abhishek; Sengupta, Ragini [Asian Journal of Chemistry, 2022, vol. 34, # 6, p. 1592 - 1596]
[2]Anupam, R. O. Y.; Devi, Elangbam Pinky; Kaldhi, Dhananjaya; Malakar, Chandi C.; Saha, Indranil; Sahoo, Abhishek; Sengupta, Ragini [Asian Journal of Chemistry, 2022, vol. 34, # 6, p. 1592 - 1596]
[3]Schaaf, Patricia; Gojic, Vladimir; Bayer, Thomas; Rudroff, Florian; Schnürch, Michael; Mihovilovic, Marko D. [ChemCatChem, 2018, vol. 10, # 5, p. 920 - 924]
  • 87
  • [ 705-28-2 ]
  • 3-(2-azido)ethyl-6-(trifluoromethoxy)benzothiazol-2-imine [ No CAS ]
  • 6-(trifluoromethoxy)-3-(2-(4-(3-(trifluoromethyl)phenyl)-1,2,3-triazol-1-yl)ethyl)benzothiazol-2-imine [ No CAS ]
YieldReaction ConditionsOperation in experiment
66% With copper(II) sulfate; sodium L-ascorbate In tetrahydrofuran; water at 20℃; for 2h; Inert atmosphere;
Reference： [1]Sweeney, Joseph B.; Rattray, Marcus; Pugh, Victoria; Powell, Lucy A. [ACS Medicinal Chemistry Letters, 2018, vol. 9, # 6, p. 552 - 556]
  • 88
  • [ 705-28-2 ]
  • [ 107047-10-9 ]
  • C16H11BrF3N3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With copper(ll) sulfate pentahydrate; sodium L-ascorbate In ethanol; water at 20℃;
With copper(ll) sulfate pentahydrate; sodium L-ascorbate In ethanol; water at 20℃; 2 4.1.1.2 1-(4-bromobenzyl)-4-(3-chlorophenyl)-1H-1,2,3-triazole (4) General procedure: A flask charged with 1-(azidomethyl)-4-bromobenzene (3) (1.20g 5.63mmol), 1-chloro-3-ethynylbenzene (0.78g, 5.63mmol) was dissolved in anhydrous ethanol (30ml). L-Sodium ascorbate (0.45g, 2.25mmol), copper sulfate pentahydrate (0.29g, 1.13mmol) and water (3ml) were then add onto the mixture. The reaction mixture was stirred at room temperature overnight. After filtration and concentration in vacuo, the residue was purified by silica gel flash chromatography (PE/AcOEt=3:1) affording (4) as white solid (1.31g, 66.7%)
Reference： [1]Pan, Xiaoyan; Liang, Liyuan; Si, Ru; Wang, Jin; Zhang, Qingqing; Zhou, Huaxin; Zhang, Lin; Zhang, Jie [European Journal of Medicinal Chemistry, 2019, vol. 163, p. 1 - 9]
[2]Shan, Yuanyuan; Si, Ru; Wang, Jin; Zhang, Qingqing; Zhou, Huaxin; Song, Jie; Zhang, Jie; Chen, Qinhua [European Journal of Medicinal Chemistry, 2019, vol. 164, p. 440 - 447]

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(trifluoromethyl)benzene
Chemistry
Organic Building Blocks
Aryls
Historical Records

Related Functional Groups of
[ 705-28-2 ]

Aryls

Chemical Structure| 88444-81-9

[ 88444-81-9 ]

3',5'-Bis(trifluoromethyl)phenylacetylene

Similarity: 1.00

Chemical Structure| 705-31-7

[ 705-31-7 ]

4-(Trifluoromethyl)phenylacetylene

Similarity: 1.00

Chemical Structure| 704-41-6

[ 704-41-6 ]

1-Ethynyl-2-(trifluoromethyl)benzene

Similarity: 0.86

Chemical Structure| 98-08-8

[ 98-08-8 ]

(Trifluoromethyl)benzene

Similarity: 0.84

Chemical Structure| 729-81-7

[ 729-81-7 ]

1,3,5-Tris(trifluoromethyl)benzene

Similarity: 0.84

Alkynes

Chemical Structure| 88444-81-9

[ 88444-81-9 ]

3',5'-Bis(trifluoromethyl)phenylacetylene

Similarity: 1.00

Chemical Structure| 705-31-7

[ 705-31-7 ]

4-(Trifluoromethyl)phenylacetylene

Similarity: 1.00

Chemical Structure| 704-41-6

[ 704-41-6 ]

1-Ethynyl-2-(trifluoromethyl)benzene

Similarity: 0.86

Trifluoromethyls

Chemical Structure| 88444-81-9

[ 88444-81-9 ]

3',5'-Bis(trifluoromethyl)phenylacetylene

Similarity: 1.00

Chemical Structure| 705-31-7

[ 705-31-7 ]

4-(Trifluoromethyl)phenylacetylene

Similarity: 1.00

Chemical Structure| 704-41-6

[ 704-41-6 ]

1-Ethynyl-2-(trifluoromethyl)benzene

Similarity: 0.86

Chemical Structure| 98-08-8

[ 98-08-8 ]

(Trifluoromethyl)benzene

Similarity: 0.84

Chemical Structure| 401-79-6

[ 401-79-6 ]

1-Methyl-3-(trifluoromethyl)benzene

Similarity: 0.84