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CAS No. : | 143879-80-5 |
Formula : | C7H2F3N |
M.W : | 157.09 |
SMILES Code : | N#CC1=CC=C(F)C(F)=C1F |
MDL No. : | MFCD00013288 |
InChI Key : | KTPHYLJFAZNALV-UHFFFAOYSA-N |
Pubchem ID : | 518936 |
GHS Pictogram: | ![]() |
Signal Word: | Danger |
Hazard Statements: | H301+H311+H331-H315-H319-H227 |
Precautionary Statements: | P501-P261-P270-P210-P271-P264-P280-P370+P378-P337+P313-P305+P351+P338-P361+P364-P332+P313-P301+P310+P330-P302+P352+P312-P304+P340+P311-P403+P233-P403+P235-P405 |
Class: | 6.1 |
UN#: | 3276 |
Packing Group: | Ⅲ |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 31.03 |
TPSA ? Topological Polar Surface Area: Calculated from | 23.79 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 1.57 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 1.94 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 3.24 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 2.74 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 3.07 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 2.51 |
Log S (ESOL):? ESOL: Topological method implemented from | -2.44 |
Solubility | 0.571 mg/ml ; 0.00363 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (Ali)? Ali: Topological method implemented from | -2.06 |
Solubility | 1.36 mg/ml ; 0.00863 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -3.31 |
Solubility | 0.0775 mg/ml ; 0.000493 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) | No |
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 | -5.88 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) | 1.82 |
* 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 |
---|---|---|
43% | With N-ethyl-N,N-diisopropylamine; In ISOPROPYLAMIDE; at 80℃; for 0.5h; | Example 4 1-(4-Amino-8-fluoro-quinazolin-7-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one (Compound 4); <strong>[143879-80-5]2,3,4-Trifluoro-benzonitrile</strong> (3.00 g, 19.1 mmol) is mixed with dimethylacetamide (30 mL). Formamidine acetate (1.99 g, 19.1 mmol) and diisopropylethyl amine (10 mL, 57.3 mmol) are added, and the resulting reaction mixture is slowly heated. Upon heating, the starting heterogeneous mixture slowly turns into a homogeneous solution. At 80° C., precipitates start to form. The reaction mixture proceeds at 80° C. for 30 minutes before it is cooled and filtered. The collected solid is further washed with DCM to afford 1.50 g of 7,8-Difluoro-quinazolin-4-ylamine (43percent yield) as white solid. LC/MS found m/z=182 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a mixture of NaH (16.6 g, 657 mmol, dry) in THF (150 mL) was added dropwise over 30 min with stirring at 0-5° C. a solution of diethyl malonate (104.7 g, 654 mmol) in THF (120 mL). To this translucent mixture was then immediately added a solution of <strong>[143879-80-5]2,3,4-<strong>[143879-80-5]trifluorobenzonitrile</strong></strong> (47.7 g, 304 mmol) in THF (50 mL) dropwise with stirring at 0-5° C. The ice bath was then removed and the mixture allowed to stir at room temperature for 4 days. The clear yellow reaction was then diluted with 1 M HCl (350 mL), 4 N HCl was added to pH 2 (paper), and the mixture was extracted with 1:1 ether/hexanes (1.x.350 mL, 1.x.200 mL). The combined organic layers were washed with brine (1.x.300 mL), dried (Na2SO4), and concentrated to afford the title compound (88.1 g, 98percent) as a 1.35:1 mixture of regioisomers. 1H NMR of major (desired) regioisomer (300 MHz, CDCl3) delta 7.51 (ddd, J=8.7 Hz, 4.6 Hz, 1.8 Hz, 1H), 7.29 (dt, J=8.9 Hz, 7.2 Hz, 1H), 5.12 (s, 1H), 4.35-4.20 (m, 4H), 1.31 (t, 7.2 J=Hz, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; at 75℃; for 17h; | 6,7-Difluoro-1H-inidazole-3-amine: [0237]; 0.32 cm3 of hydrazine monohydrate is added to 0.46 cm3 of <strong>[143879-80-5]2,3,4-<strong>[143879-80-5]trifluorobenzonitrile</strong></strong> in 10 cm3 of absolute ethanol. The medium is heated at about 75° C. for 17 hours, followed by addition of 10 cm3 of ethyl acetate, 5 cm3 of tetrahydrofuran and 5 cm3 of distilled water. The organic phase is separated out after settling the phases and is washed with 10 cm3 of distilled water and then with 10 cm3 of saturated aqueous sodium chloride solution. The organic phase is separated out after settling the phases, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50° C.). The residue obtained is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 mum; diameter 1.5 cm), eluting with a cyclohexane/ethyl acetate mixture (50/50 by volume). The fractions containing the expected product are combined and then evaporated under reduced pressure (2 kPa; 40° C.); after drying (90 Pa; 40° C.), 100 mg of 6,7-difluoro-1H-indazole-3-amine are obtained in the form of a white solid melting at 183° C. [0238] 1H NMR spectrum (300 MHz, (CD3)2SO d6, delta in ppm): 5.57 (unresolved complex: 2H); 6.93 (mt: 1H); 7.52 (ddd, J=8.5-4.5 and 1Hz: 1H); 12.01 (unresolved complex: 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With sodium hydride; In tetrahydrofuran; at 0 - 20℃; for 96h; | To a mixture of NaH (16. 6 g, 657 mmol, dry) in THF (150 ML) was added dropwise over 30 min with stirring at 0-5 °C a solution of diethyl malonate (104.7 g, 654 mmol) in THF (120 mL). To this translucent mixture was then immediately added a solution of 2,3, 4-<strong>[143879-80-5]trifluorobenzonitrile</strong> (47.7 g, 304 mmol) in THF (50 mL) dropwise with stirring at 0-5 °C. The ice bath was then removed and the mixture allowed to stir at room temperature for 4 days. The clear yellow reaction was then diluted with 1 M HCl (350 mL), 4 N HCl was added to PH-2 (paper), and the mixture was extracted with 1: 1 ether/hexanes (1 x 350 mL, 1 x 200 mL). The combined organic layers were washed with brine (1 x 300 mL), dried (Na2SO4), and concentrated to afford the title compound (88.1 g, 98percent) as a 1. 35 : 1 mixture OF REGIOISOMERS. 1H NMR of major (desired) regioisomer (300 MHz, CDC13) 8 7.51 (ddd, J = 8.7 Hz, 4.6 Hz, 1.8 Hz, 1H), 7.29 (dt, J = 8.9 Hz, 7.2 Hz, 1H), 5.12 (s, 1H), 4.35-4. 20 (m, 4H), 1.31 (t, 7.2 7= HZ, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ISOPROPYLAMIDE; at 80℃; for 2h; | 4- 4-CYANO-2, 3-DIFLUORO-PHENYL)-PIPERAZINE-L-CARBOXYLIC ACID TERT-BUTYL ester To a solution OF N-BOC-PIPERAZINE (0.65 g) in DMA (20 mL) was slowly added a solution of 2, 3, 4-<strong>[143879-80-5]trifluorobenzonitrile</strong> (0.49 g) in DMA (10 mL). The reaction mixture was stirred for 2 hours at 80°C. After such time the solvent was removed in vacuo and purified by column chromatography (SIO2) to yield the title compound as white solid (0.76 g). | |
In ISOPROPYLAMIDE; at 80℃; for 2h; | To a solution of N-Boc-Piperazine (0.65 g) in DMA (20 mL) was slowly added a solution of <strong>[143879-80-5]2,3,4-<strong>[143879-80-5]trifluorobenzonitrile</strong></strong> (0.49 g) in DMA (10 mL). The reaction mixture was stirred for 2 hours at 80° C. After such time the solvent was removed in vacuo and purified by column chromatography (SiO2) to yield the title compound as white solid (0.76 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrazine; In ethanol; water; at 75℃; for 17h; | 0.32 cm3 of hydrazine monohydrate is added to 0.46 cm3 of <strong>[143879-80-5]2,3,4-<strong>[143879-80-5]trifluorobenzonitrile</strong></strong> in 10 cm3 of absolute ethanol. The medium is heated at about 75° C. for 17 hours and then 10 cm3 of ethyl acetate, 5 cm3 of tetrahydrofuran and 5 cm3 of distilled water are added. The organic phase is separated out after settling of the phases has taken place, and is washed again with 10 cm3 of distilled water and then with 10 cm3 of saturated aqueous sodium chloride solution. The organic phase is separated out after settling of the phases has taken place, dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50° C.). The residue obtained is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 mum; diameter 1.5 cm), eluting with a cyclohexane/ethyl acetate mixture (50/50 by volume). The fractions containing the expected product are combined and then evaporated under reduced pressure (2 kPa; 40° C.); after drying (90 Pa; 40° C.), 100 mg of 6,7-difluoro-1H-indazole-3-amine are obtained in the form of a white solid melting at 183° C. [0561] 1H NMR spectrum (300 MHz, (CD3)2SO-d6, delta in ppm): 5.57 (unresolved peak: 2H); 6.93 (mt: 1H); 7.52 (ddd, J=8.5-4.5 and 1 Hz: 1H); 12.01 (unresolved peak: 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 100℃; for 3h; | <strong>[143879-80-5]2,3,4-<strong>[143879-80-5]trifluorobenzonitrile</strong></strong> (3 g, 19 mmol), tert-butyl carbazate (4 g, 30 mmol) and Hunig's base were dissolved in dioxane (10 mL) and heated at 100° C. for 3 d. The mixture was concentrated and then partitioned between toluene (25 mL) and water (29 mL). The toluene layer was added to a column and chromatographed (silica gel, 10 to 40percent ethyl acetate in hexanes) to give product as an oil. Recrystallization from ethyl acetate/hexanes gave N'-(4-cyano-2,3-difluoro-phenyl)-hydrazinecarboxylic acid tert-butyl ester (1.16 g, 22percent) as a white powder. A second crop (0.5 g, 10percent) was obtained as a slightly pinkish powder. LCMS (m/z): M+H=170.1 (loss of BOC). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | In tetrahydrofuran; at 20℃; for 4h; | E=XAMPLES 43 AND 44Preparation of 2-[4-(dimethylamino)-2,3-difluorophenyl]-4,5,6,7-tetrahydro-1 ,3- benzothiazol-7-ol (Example 43) and [4-(7-ethoxy-4,5,6,7-tetrahydro-1 ,3-benzothiazol-2-yl)-2,3- difluorophenyl]dimethylamine (Example 44) Step A. 4-(dimethylamino)-2,3-difluorobenzonitrileA mixture of 2, 3, 4-trifluoro benzonitrile (1.686 g, 10.73 mmol) in dimethylamine (2M solution in THF, 16.1 ml_, 32.2 mmol) was stirred at room temperature for 4 hours, quenched with saturated NaHCO3 solution, then extracted with ether three times. The combined extracts were washed with H2O, brine, then dried over Na2SO4, filtered and concentrated. The residue was separated by silica gel column, eluting with hexane/EtOAc = 3:1, to give 1.164 g (60percent) of 4- (dimethylamino)-2,3-difluorobenzonrtrile as a white solid. 4-(dimethylamino)-2,3-difluorobenzonitrile, MS: m/z 183 (M + H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 20℃; for 68h; | Scheme 21[0368] To <strong>[143879-80-5]2,3,4-<strong>[143879-80-5]trifluorobenzonitrile</strong></strong> (265 mg, 1.68 mmol) in a flask, a solution of D- leucine amide hydrochloride (282 mg, 1.68 mmol) and DIEA (0.880 mL, 5.06 mmol) in DMSO (5 mL) was added. After being stirred at room temperature for 68 h, water and EtOAc were added. The organic phase was separated, washed with water, dried over Na2S04, concentrated in vacuo. The residue was purified by a silica gel column, eluted with 0-70percent EtOAc in hexane to give (R)-2-(4-cyano-2,3-difluorophenylamino)-4-methylpentanamide (113 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11.4% | With potassium phosphate; In 1-methyl-pyrrolidin-2-one; at 115℃; for 18h;Inert atmosphere; | 2.5 g (15.9 mmol) <strong>[143879-80-5]2,3,4-<strong>[143879-80-5]trifluorobenzonitrile</strong></strong>, 10.9 g (52.5 mmol) 6H-benzimidazolo[1 ,2- a]benzimidazole and 27.0 g (0.127 mol) potassium phosphate tribasic in 50 ml NMP (N-Methyl- 2-pyrrolidon) are stirred at 1 15 °C under nitrogen for 18 h. The reaction mixture is filtered hot and the organic phase is poured on water. The product is filtered of. Column chromatography on silica gel with chloroform gives 1 .3 g (1 1.4 percent) of the product. 1H NMR (300 MHz, DMSO-D6): rotamers: delta 8.55-8.82 (m, 2H); 6.41 -8.07 (m, 24H) MS (APCI(pos), m/z): 719 (M+1). |
Tags: 143879-80-5 synthesis path| 143879-80-5 SDS| 143879-80-5 COA| 143879-80-5 purity| 143879-80-5 application| 143879-80-5 NMR| 143879-80-5 COA| 143879-80-5 structure
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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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