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CAS No. : | 139301-27-2 |
Formula : | C7H6BF3O3 |
M.W : | 205.93 |
SMILES Code : | C1=C(OC(F)(F)F)C=CC(=C1)B(O)O |
MDL No. : | MFCD01074648 |
InChI Key : | HUOFUOCSQCYFPW-UHFFFAOYSA-N |
Pubchem ID : | 2734386 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61.1% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,2-dimethoxyethane; water at 130℃; Sealed tube | 4- (trifluoromethoxy) phenylboronic acid (254mg, 1.24mmol), 3-bromo -N- [6- (2,6- dimethyl - morpholin-4-yl) - pyridine 3-yl] -4-methyl -benzamide 5 (250mg, 0.62mmol), Pd (PPh 3) 4 (36mg, 0.03mmol), Na 2 CO 3 (2.0Maqueous solution, 1.23mL, 2.4mmol) and a mixture of DME (4.5mL) in a sealed tube and heated at130 ° C overnight. The reaction mixture was diluted with EtOAc and water. Theaqueous layer was extracted with EtOAc. The combined organic layers were washedwith brine and concentrated to give a crude product, which was then purified bypreparative mass triggered HPLC (C 18 column and eluted with 0.05percent TFA in CH 3CN-H 2 O elution) to give N - (6 - ((2S, 6R) -2,6- dimethyl-morpholino)pyridin-3-yl) -2-methyl-4 '- (trifluoromethoxy) biphenyl-3-carboxylic amide(183.5mg, yield 61.1percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In methanol; water; toluene;Inert atmosphere; Reflux; | General procedure: To a solution of bromobiphenylaldehyde (6, 260 mg, 1 mmol) and various phenyl boronic acids (7a-j, 1 mmol) in 2 M aqueous sodium carbonate (2 mL) and toluene/ethanol (9:3 mL) is added a catalytic amount (0.4% mol) of tetrakis-triphenylphosphine palladium, and the mixture was reflux under argon atmosphere for 2-3 h. After completion of reaction, the suspension is cooled and extracted with ethyl acetate (3 × 30 mL) and the organic phase was washed with water and brine, dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure to get the crude product. This residue was further purified by column chromatography using ethyl acetate and hexane to afford the pure terphenylaldehydes (8). |
69% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene;Inert atmosphere; Reflux; | General procedure: To a solution of bromobiphenyl aldehyde 11 (390 mg, 1.5 mmol) and 4-fluoro phenyl boronic acid 12a (209.8 mg, 1.5 mmol) in 2 M aqueous sodium carbonate (2 mL) and toluene/ethanol (12:4 mL) is added a catalytic amount (0.4 mol %) of tetrakis-triphenylphosphine palladium, and the mixture was heated to reflux under argon atmosphere for 3-4 h. After completion of the reaction, the reaction mixture is cooled to room temperature and extracted with ethyl acetate (3 x 30 mL) and the organic phase was extracted with water and brine solution, dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure to get the crude product. This crude product was further purified by column chromatography (10% ethyl acetate and hexane) to afford the pure terphenyl aldehydes (13a) as a white solid in 310 mg, 74% yield; mp: 135-136 C; 1H NMR (300 MHz, CDCl3): δ 7.12-7.19 (m, 2H), 7.57-7.73 (m, 6H), 7.78 (d, 2H, J = 8.3 Hz), 7.96 (d, 2H, J = 8.3 Hz), 10.06 (s, 1H); (ESI) MS: m/z 277 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With bis-triphenylphosphine-palladium(II) chloride; triethylamine; In water; N,N-dimethyl-formamide; at 80℃; for 4h; | General procedure: Pd(PPh3)2Cl2 (23 mg, 0.03 mmol), 4-trifluoromethoxyphenylboronic acid (73 mg, 0.35 mmol), compound 15 (100 mg, 0.32 mmol) and TEA (91 mg, 0.90 mmol) were added to a solution of DMF (5 mL) and H2O (0.5 mL). The mixture was stirred at 80 oC for 4 h. Water (10 mL) and EtOAc (30 mL) were added to the reaction. The layers were separated. The aqueous layer was extracted using EtOAc (10 mL). The combined organic extracts were dried over anhydrous Na2SO4. The solvent was removed under reduced pressure, and the resulting residue was purified via silica gel column chromatography using petroleum ether/EtOAc (5/1) to give 16 (67 mg, 48 percent) as a yellow solid. |
73% | With bis-triphenylphosphine-palladium(II) chloride; triethylamine; In water; N,N-dimethyl-formamide; at 85℃; | General procedure: Weigh 2,4-dichloro-7H-pyrrolopyrimidine (372 mg, 1 eq),P-trifluoromethoxyphenylboronic acid (1000 mg, 1.1 eq), triethylamine (1.2 eq),Bis(triphenylphosphine)palladium(II) chloride (0.1eq), N,N-dimethylformamide(28.5 ml), water (0.5 ml) was added to the flask and the temperature was raised to 85°C for 4 hours.After stopping the reaction, add water to the reaction solution100ml, stirring, ethyl acetate (20ml*4) extraction,The ester layer was dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography.(petroleum ether:ethyl acetate=20:1)Obtained solid (680 mg, 41percent) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61.1% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 130℃;Sealed tube; | 4- (trifluoromethoxy) phenylboronic acid (254mg, 1.24mmol), 3-bromo -N- [6- (2,6- dimethyl - morpholin-4-yl) - pyridine 3-yl] -4-methyl -benzamide 5 (250mg, 0.62mmol), Pd (PPh 3) 4 (36mg, 0.03mmol), Na 2 CO 3 (2.0Maqueous solution, 1.23mL, 2.4mmol) and a mixture of DME (4.5mL) in a sealed tube and heated at130 C overnight. The reaction mixture was diluted with EtOAc and water. Theaqueous layer was extracted with EtOAc. The combined organic layers were washedwith brine and concentrated to give a crude product, which was then purified bypreparative mass triggered HPLC (C 18 column and eluted with 0.05% TFA in CH 3CN-H 2 O elution) to give N - (6 - ((2S, 6R) -2,6- dimethyl-morpholino)pyridin-3-yl) -2-methyl-4 '- (trifluoromethoxy) biphenyl-3-carboxylic amide(183.5mg, yield 61.1%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | General procedure: PhB(OH)2 (0.15 g, 1.2 mmol, 1.2 equiv), Cu(OAc)2 (0.036 g, 0.2 mmol, 0.2 equiv) and myristicacid (0.091 g, 0.4 mmol, 0.4 equiv) were dissolved in toluene (2 mL, 0.5M). The reaction wasstirred, 2,6-lutidine (0.12 mL, 1 mmol, 1 equiv) and <strong>[52562-19-3]2-isopropenylaniline</strong> (0.14 mL, 1 mmol, 1equiv) were added. The reaction was stirred at room temperature exposed to air for 24 h.TEMPO (0.031 g, 0.2 mmol, 0.2 equiv) and toluene (8 mL, 0.1M overall) were then added. Theflask was purged with O2, put under an O2 atmosphere using an O2 balloon and stirred for 24 h at120 oC. Filtration of the cooled reaction mixture through a pad of silica gel with ethyl acetate(100 mL), and subsequent evaporation of the solvent in vacuo afforded crude mixtures. Flashchromatography of the resulting crude mixture on silica gel (0-5% diethyl ether in hexanesgradient) afforded the known indole 2g (0.11 g, 53% yield) as a yellow liquid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; silver trifluoroacetate; In methanol; at 60℃;Schlenk technique; Inert atmosphere; | General procedure: A mixture of N-pyrimidyl indoles 1 (0.20 mmol, 1.0 equiv.), arylboronicacids 2 (0.40 mmol, 2.0 equiv.),AgOOCF3 (0.80 mmol, 4.0 equiv.), and [RhCp*Cl2]2(0.002 mmol, 0.01 equiv.) were combined in MeOH (1.0 mL) in a dried Schlenk tubeunder a argon atmosphere. The resulting mixture was stirred at 60 C andmonitored by TLC. Uponcompletion or no further improvement of reaction, the reaction mixture wascooled to room temperature and added with Et3N (1 mL). Then themixture was filtered through a pad of silica gel eluting with 25 mL of CH2Cl2.The solvent was removed under reduced pressure and the residue was purified byflash chromatography on silica gel to afford the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
509mg | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; lithium chloride; In 1,4-dioxane; water; at 100℃; for 3.5h; | 12184] A mixture of 500 mg of methyl 6-bromobenzo[b] thiophene-2-carboxylate, 494 mg of 4-(trifluoromethoxy) phenylboronic acid, 407 mg of lithium chloride, 352 mg of sodium carbonate, 107 mg of tetrakis(triphenylphosphine) palladium (0), 20 ml of 1 ,4-dioxane, and 10 ml of water was stirred for 3.5 hours a: 1000 C. Afier being cooled to room temperature, the reaction mixture was concentrated under reduced pressure. Chloroform was added to the residues, and insoluble matter was separated by filtration. Afier water was added to the filtrate, extraction was performed using chloroform. The organic layer was washed with saturated saline, dried over magnesium sulfate, and then concentrated under reduced pressure. The residues were subjected to silica gel column chromatography, thereby obtaining 509mg of methyl 6-(4-trifluoromethoxyphenyl)benzo[b]thiophene-2-car- boxylate (hereinafier, described as a ?compound 45 of the present invention?)12185] Compound 45 of the Present Invention 12186] ?H-NMR (CDC13) oe: 8.09 (s, 1H), 8.03 (s, 1H),7.96-7.94 (n, 1H), 7.68-7.66 (m, 2H), 7.62-7.60 (m, 1H),7.34-7.32 (m, 2H), 3.97 (s, 3H) |
509 mg | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; lithium chloride; In 1,4-dioxane; water; at 100℃; for 3.5h; | A mixture of 500 mg of <strong>[360576-01-8]methyl 6-bromobenzo[b]thiophene-2-carboxylate</strong>, 494 mg of 4-(trifluoromethoxy)phenylboronicacid, 407 mg of lithium chloride, 352 mg of sodium carbonate, 107 mg of tetrakis(triphenylphosphine)palladium(0), 20 ml of 1,4-dioxane, and 10 ml of water was stirred for 3.5 hours at 100C. After being cooled to room temperature,the reaction mixture was concentrated under reduced pressure. Chloroform was added to the residues, and insolublematter was separated by filtration. After water was added to the filtrate, extraction was performed using chloroform. Theorganic layer was washed with saturated saline, dried over magnesium sulfate, and then concentrated under reducedpressure. The residues were subjected to silica gel column chromatography, thereby obtaining 509 mg of methyl 6-(4-trifluoromethoxyphenyl)benzo[b]thiophene-2-caboxylate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate; bis[tris( 1,1-dimethylethyl)phosphine]-palladium; In 1,4-dioxane; water; at 80℃; for 16.0h;Inert atmosphere; | A mixture of A-14 (300.00 mg, 1.52 mmol), [4-(trifluoromethoxy)phenyllboronic acid (344.31 mg, 1.67 mmol), K3P04 (645.30 mg, 3.04 mmol) and Pd(t-Bu3P)2 (155.36 mg, 304.00 jimol) in dioxane (20.00 mL) and H20 (2.0 mL) was stirredunder N2 at 80 °C for 16 hours. The mixture was diluted with EtOAc (20 mL), filtered through silica gel, and eluted with EtOAc (10 mL), and the filtrate was concentrated to give the crude product which was purified by Prep-HPLC to give Compound 12 as a solid. ?H NMR (400 MHz, CDC13) oe11 8.54 (d, 1H), 8.08 - 7.90 (m, 1H), 7.78 - 7.62 (m, 3H), 7.34 (d, 2H), 6.99 (dd, 1H), 6.69 - 6.50 (m, 1H). LCMS R = 1.209 mm in 2.0 mm chromatography, MS ESI calcd. forC,4H,0F3N20 [M+H1 279.1, found 278.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
170 mg | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; water; at 90℃; for 16h;Inert atmosphere; | A mixture of A-63 (1 g, 6.71mmol), [4-(trifluoromethoxy)phenyl]- boronic acid (1.52 g, 7.38 mmol), Pd(dppf)Cl2.CH2Cl2 (822.23 mg, 1.01 mmol) and Cs2C03 (4373.74 mg, 13.42 mmol) in 1,4-dioxane (20 mL) and water (4 mL) under N2 was stirred at 90 C for 16 hours. After cooling, the reaction mixture was diluted with EtOAc (20 mL), and filtered through a Celite pad, eluted with EtOAc (20 mL), and concentrated. The residue was purified by flash chromatography on silica gel (EtOAc in PE = 0percent to 3percent to 8percent) to afford A-108 (250 mg, 0.91 mmol) as a solid. 1H NMR (400MHz, CDC13) _ = 8.79 (d, 1H), 8.65 (d, 1H), 8.05 (d, 2H), 7.37 (d, 2H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 20℃;Inert atmosphere; | General procedure: A mixture of (4-iodophenyl)(methyl)sulfane (Compound 4A) (500 mg, 2 mmol), 4-bromophenylboronic acid (400 mg, 2 mmol), Na2CCh (636 mg, 6 mmol), and Pd(PPh3)4 (115 mg, 0.1 mmol) in toluene/EtOH/H20 (20/10/4 mL) was stirred at 80 C under nitrogen overnight The mixture was concentrated under reduced pressure. The residue was purified with flash column chromatography on silica gel (ethyl acetate in petroleum ether, 10% v/v) to afford Compound 4B. LC-MS (ESI) m/z: non-ionizable compound under routine conditions used. - NMR (CDCb, 500 MHz): d (ppm) 2.52 (s, 3H), 7.32 (d, J= 8.5 Hz, 2H), 7.43 (d, J= 8.5 Hz, 2H), 7.48 (d, J= 8.5 Hz, 2H), 7.55 (d, J= 8.5 Hz, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water;Reflux; Inert atmosphere; | General procedure: A mixture of 2,4-dibromothiazole (Compound 8A) (3.9 g, 16 mmol), 3,4- dichlorophenylboronic acid (3.05 g, 16 mol), Pd(dppf)C12 (0.7 g, 0.87 mmol), and cesium carbonate (15 g, 46 mmol) in DME (120 mL) and water (10 mL) was heated at reflux under nitrogen overnight. The reaction mixture was diluted with water (100 mL) and extracted with ethyl acetate (200 mL x 2). The combined extracts were washed with water (200 mL) and brine (200 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified with flash column chromatography on silica gel (ethyl acetate in petroleum ether, from 0% to 10% v/v) to yield Compound 8B. LC-MS (ESI) m/z: 308 [M+H]t | |
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water;Inert atmosphere; Reflux; | General procedure: A mixture of 2,4-dibromothiazole (Compound 8A) (3.9 g, 16 mmol), 3,4- dichlorophenylboronic acid (3.05 g, 16 mol), Pd(dppf)Cl2 (0.7 g, 0.87 mmol), and cesium carbonate (15 g, 46 mmol) in DME (120 mL) and water (10 mL) was heated at reflux under nitrogen overnight. The reaction mixture was diluted with water (100 mL) and extracted with ethyl acetate (200 mL x 2). The combined extracts were washed with water (200 mL) and brine (200 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified with flash column chromatography on silica gel (ethyl acetate in petroleum ether, from 0% to 10% v/v) to yield Compound 8B. LC-MS (ESI) m/z: 308 [M+H]+. |
Tags: 139301-27-2 synthesis path| 139301-27-2 SDS| 139301-27-2 COA| 139301-27-2 purity| 139301-27-2 application| 139301-27-2 NMR| 139301-27-2 COA| 139301-27-2 structure
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Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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