Structure of 52334-81-3
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CAS No. : | 52334-81-3 |
Formula : | C6H3ClF3N |
M.W : | 181.54 |
SMILES Code : | C1=C(C(F)(F)F)C=NC(=C1)Cl |
MDL No. : | MFCD00042225 |
InChI Key : | JFZJMSDDOOAOIV-UHFFFAOYSA-N |
Pubchem ID : | 92342 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.17 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 34.25 |
TPSA ? Topological Polar Surface Area: Calculated from |
12.89 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.79 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.7 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.91 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.18 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.01 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.72 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.0 |
Solubility | 0.18 mg/ml ; 0.00099 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.62 |
Solubility | 0.432 mg/ml ; 0.00238 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.53 |
Solubility | 0.0541 mg/ml ; 0.000298 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.49 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
2.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.8 |
* 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 |
---|---|---|
15.4 g | Stage #1: With hydrazine In ethanol at 100℃; for 3 h; Stage #2: With hydrogenchloride In ethanol |
(1) 2-chloro-5- (trifluoromethyl) pyridine (25g), hydrazine was added to the catcher (100percent) (100) in ethanol (60), and stirring for 3 hours at 100 ° C, concentrated under reduced pressure to the reaction solution and the organic layer was separated by adding chloroform and water to the residue, dried over anhydrous sodium sulfate, evaporated to remove the solvent under reduced pressure, and 4N hydrochloric acid to the residue-by adding an ethanol solution of 5- (trifluoromethyl Romero butyl) pyridine-2-yl hydrazine hydrochloride (15.4g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 100℃; | Reference Example 16 A mixture of ethyl3-methyl-lH-pyrazole-4-carboxylate (23.10 g),2-chloro-5- (trifluoromethyl) pyridine (25.09 g), potassium carbonate (19.00 g) and N, N-dimethylformamide (300 ml) was stirred overnight at100 C. The reaction mixture was poured into dilute hydrochloric acid, and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried(MgS04) and <Desc/Clms Page number 126>concentrated. The residue was subjected to silica gel column chromatography, and ethyl3-methyl-l- [5- (trifluoromethyl)-2-pyridyl3-lH-pyrazole-4-carboxylate (40.22 g, yield 97%) was obtained as colorless crystals from a fraction eluted with ethyl acetate-hexane (1: 4, volume ratio). The crystals were recrystallized from ethyl acetate-hexane. melting point: 88-89 C. H-NMR(CDC13)8 : 1.38 (3H, t, J=7.2 Hz), 2.57 (3H, s), 4.34 (2H, q, J=7.2 Hz), 8.05(1H, dd, J=2.4, 9.3 Hz), 8.10(1H, d, J=9.3 Hz), 8.64-8. 72(1H, m), 9.00(1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
[0084] A reaction vessel was charged with sodium hydride (as a 60% oil dispersion, 7.2 g, 180 mmol), DME (60 ml) and 2-chloro-5-trifluoromethylpyridine (10 g, 55.1 mmol). 3-Chloro-4-fluoroacetophenone (9.8 g, 56.9 mmol) in DME (20 ml) was added in portions to the mixture under nitrogen at room temperature. The mixture was stirred at ambient temperature for one hour then at 40-45 C. overnight. Upon the completion of the reaction, the mixture was cooled to 5 C. and 10% aqueous sodium hydroxide solution (30 ml) was slowly added to the reaction mixture followed by methanol (60 ml) then hydroxylamine hydrochloride (19.1 g, 357 mmol). The mixture was heated to 72 C. for 4 hours then cooled and diluted with water (1500 ml) with stirring. The resulting solid was removed by filtration and dried under vacuum. It was then slurried in cyclohexane (100 ml) then filtered, washing with further cyclohexane. The crude solid was purified by dissolution in diethylether (50 ml) and passage through silica gel, washing with further diethylether. Concentration of the filtrate afforded 15.56 g (85%) of the title compound. [0085] Mass Spectrum: Found: (M-H)-331 [0086] HPLC (lambda=220-230 nm) RT 3.7 min |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
[0159] A reaction vessel was charged with sodium hydride (as a 60% oil dispersion, 5.52 g, 1 38 mmol), DME (23 ml) and 2-chloro-5-trifluoromethylpyridine (7.06 g, 42 mmol). 3,5-Dichloroacetophenone (8.3 g, 44 mmol) in DME (23 ml) was added in portions to the mixture under nitrogen at room temperature. The mixture was stirred at ambient temperature for one hour then at 40-45 C. overnight. Upon completion of the reaction, the mixture was cooled to 5 C. and 10% aqueous sodium hydroxide solution (23 ml) was slowly added to the reaction mixture followed by methanol (46 ml) then hydroxylamine hydrochloride (14.5 g, 210 mmol). The mixture was heated to 72 C. for 4 hours then cooled and diluted with water (1500 ml) with stirring. The resulting solid was removed by filtration and dried under vacuum. It was then slurried in cyclohexane (100 ml) then filtered, washing with further cyclohexane. The crude solid 13.30 g (86%) was used in subsequent reactions without further purification. [0160] Mass Spectrum: Found: (M-H)-348 [0161] HPLC (?,=220-230 nm) RT 3.83 min |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 110℃; for 12h; | Step 2 2-(5-Bromo-2-methylphenoxy)-5-(trifluoromethyl)pyridine To a solution of <strong>[36138-76-8]5-bromo-2-methylphenol</strong> (1.0 g, 0.005 mol) in DMF (10 mL) was added K2CO3 (1.38 g, 0.01 mol) at RT. 2-Chloro-5-(trifluoromethyl)pyridine (908 mg, 0.005 mol) was added and the reaction was refluxed at 110 C. for 12 h. The reaction mixture was quenched with water and extracted with EtOAc three times. The organic extract was washed with water and brine, dried over sodium sulfate and concentrated under reduced pressure to give the title compound (1.5 g, 88%). 1H NMR (500 MHz, CDCl3): delta 8.42 (s, 1H), 7.92 (d, J=2.15 Hz, 1H), 7.32 (t, J=6.45 1H), 7.23 (d, J=1.5 Hz, 1H), 7.17 (d, J=8.05 Hz, 1H), 7.03 (d, J=8.65 Hz, 1H), 2.12 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84.5% | With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 110℃; for 12.0h; | Example 61; Synthesis of 4-(3-methyl-5-(5-(trifluoromethyl)pyridin-2-yloxy)benzylidene)-N-(pyridin-3-yl)piperidine-1-carboxamide; Step 1; 2-(3-Bromo-5-methylphenoxy)-5-(trifluoromethyl)pyridine; To a solution of <strong>[74204-00-5]3-bromo-5-methylphenol</strong> (2.0 g, 0.0106 mol) in DMF (15 mL) was added K2CO3 (2.93 g, 0.02 mol) at RT. 2-Chloro-5-(trifluoromethyl)pyridine (1.94 g, 0.0106 mol) was added and the reaction was refluxed at 110° C. for 12 h. The reaction mixture was quenched with water and extracted with EtOAc three times. The total organic extract was washed with water and brine, dried over sodium sulfate and concentrated under reduced pressure to give the title compound (3 g, 84.5percent). 1H NMR (500 MHz, CDCl3): delta 8.45 (s, 1H), 7.92 (d, J=8.6 Hz, 1H), 7.26 (d, J=14.95 Hz, 1H), 7.13 (s, 1H), 7.03 (d, J=10 Hz, 1H), 6.90 (s, 1H), 2.36 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In N,N-dimethyl-formamide; at 80℃; for 6h; | Example 2; Synthesis of 3-[5-(trifluoromethyl)pyridin-2-yl]-3-azabicyclo[3.1.0]hexan-6-amine (pTSA salt)Step a: Synthesis of tert-butyl [3-(5-trifluoropyridin-2-yl)-3-azabicyclo[3.1.0]hex-6-yl] carbamateA solution of tert-butyl 3-azabicyclo[3.1.0]hex-6-ylcarbamate (0.500 g, 2.50 mmol) and 2-chloro-5-(trifluoromethyl)pyridine (0.38 mL, 3.0 mmol) in dimethylformamide (5.0 mL) was heated at 80 C. for about 6 hours. The solvent was removed under vacuum, and the residue partitioned between dichloromethane (30.0 mL) and water (20.0 mL). The organic layer was washed with brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue was purified by column chromatography using 30% ethyl acetate in hexane as eluant (silica gel 100-200 mesh) to yield the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37% | Combine <strong>[34584-69-5]3,6-dichloro-4,5-dimethyl-pyridazine</strong> (100 mg, 0.554 mmol), (R)-2-methylpiperazine (85 mg, 0.831 mmol), potassium carbonate (383 mg, 2.77 mmol) and DMF (1 mL) in vial. Heat in the microwave at 120° C. for 3.25 h. Add 2-chloro-5-trifluoromethylpyridine (181 mg, 0.997 mmol) and heat at 180° C. for 30 min. The crude reaction is purified directly by flash chromatography on silica gel (0-40percent EtOAc in heptanes) to afford the title compound as a light yellow solid (78 mg, 37percent).MS (m/z, MH+) meas. 386.4 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 1-methyl-pyrrolidin-2-one; water; at 20℃; for 3h; | Reference Production Example 6; To a mixture of 18.2 of 2-chloro-5- trifluoromethylpyridine and 100 ml of N- methylpyrrolidone was added 23.3 g of a 40% methylamine aqueous solution, and the mixture was stirred for 3 hours at room temperature. Water was poured, and the mixture was extracted three times with ethyl acetate. The combined organic layers were dried over magnesium sulfate, then, concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 17.3 g of N-methyl-(5- trifluoromethylpyridine-2-yl) -amine .Me1H-NMR (CDCl3) delta: 8.34 (s, IH), 7.60 (dd, J=8.8, 2.4Hz, IH), 6.40 (d, J=8.8Hz, IH), 4.89(br s, IH), 2.97 (d, J=5.1Hz, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79%; 15% | With bis-triphenylphosphine-palladium(II) chloride; triethylamine; n-butyl-diphenylphosphane; at 120℃; under 2280.15 Torr; for 3h;Autoclave; | Reference Example 2 (0150) Production Method of 5-(trifluoromethyl)pyridine-2-carboxylic acid ester (0151) A 100-mL autoclave was charged successively with 2-chloro-5-(trifluoromethyl)pyridine (24.55 g, 135.26 mmol), PdCl2(PPh3)2 (474 mg, 0.5 mol %), diphenylphosphinobutane (DPPB, 1.45 g, 2.5 mol %), triethylamine (24 mL) and methanol (50 mL). The atmosphere in the reaction system was replaced by carbon monoxide 3 times. After charging with carbon monoxide to a pressure of 3 atmospheres, the mixture in the autoclave was stirred under heating at 120 C. for 3 hours. After cooling to room temperature, water and ethyl acetate were added to the reaction mixture, and extraction was repeated about 3 times, followed by drying and concentration. The concentrate was subjected to column chromatography (from hexane: ethyl acetate=5:1 to ethyl acetate) to give a methyl ester compound (21.8 g, 79%) and a carboxylic acid compound (3.86 g, 15%). |
Tags: 52334-81-3 synthesis path| 52334-81-3 SDS| 52334-81-3 COA| 52334-81-3 purity| 52334-81-3 application| 52334-81-3 NMR| 52334-81-3 COA| 52334-81-3 structure
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P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
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 |
Sorry,this product has been discontinued.
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