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CAS No. : | 149125-30-4 |
Formula : | C9H4F3NO3 |
M.W : | 231.13 |
SMILES Code : | O=C1NC2=C(C=CC=C2OC(F)(F)F)C1=O |
MDL No. : | MFCD06804535 |
InChI Key : | JDVUYYNGNVYMKQ-UHFFFAOYSA-N |
Pubchem ID : | 16099928 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.11 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 6.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 48.84 |
TPSA ? Topological Polar Surface Area: Calculated from | 55.4 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 1.26 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 1.9 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 2.41 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 0.35 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 2.05 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 1.59 |
Log S (ESOL):? ESOL: Topological method implemented from | -2.62 |
Solubility | 0.56 mg/ml ; 0.00242 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (Ali)? Ali: Topological method implemented from | -2.69 |
Solubility | 0.476 mg/ml ; 0.00206 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -3.41 |
Solubility | 0.0895 mg/ml ; 0.000387 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 | -6.36 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 | 0.0 |
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) | 1.92 |
* 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 |
---|---|---|
89% | at 60 - 80℃; | General procedure: Concentrated sulfuric acid (95 mL) was heated in a flask at 60 C. Intermediates 2 (12 g, 52mmol) were slowly added in portions to maintain the temperature below 70 C. The temperature was then increased to 80 C. After 3 h, the solution was cooled to room temperature, and then poured into crushed ice with vigorous stirring. The precipitate was collected by filtration and dried under vacuum to provide the product 3. |
70% | at 55 - 80℃; for 0.166667 h; | The procedure described by Marvel et al. (see Org. Synth. Coll. Vol. I, 327) was followed. Intermediate 12 (11.9 g, 48.5 mmol) was added in small portions to 35 mL of concentrated sulfuric acid at 55° C. in a 250 mL Erlenmeyer flask. The temperature of the solution was maintained below 70° C. until all the acetamide had been added and it was increased to 80° C. for 10 minutes. The dark-colored solution was cooled to room temperature and poured onto 175 mL of crushed ice. After standing for 30 minutes, the precipitate was collected by filtration, washed three times with water, and dried under vacuum to yield indoline-2,3-dione of sufficient purity to be used in the next step (intermediate 13, 8.32 g, 70percent yield). 1H NMR (400 MHz, DMSO-d6) δ 7.15 (t, J=7.8 Hz, 1H), 7.56 (d, J=7.3 Hz, 1H), 7.64 (d, J=8.3 Hz, 1H), 11.71 (s, 1H). |
59% | Stage #1: at 65 - 80℃; for 1.5 h; Stage #2: With sodium hydroxide In chloroform; water; isopropyl alcohol at 0℃; | According to Scheme 9, concentrated sulfuric acid (40 mL) was heated to 65° C. and poured into a flask containing the crude 2-(trifluoromethoxy)-α-oximinoanilide from Example 1.1. The mixture was stirred at 65° C. until homogeneous and then the temperature was increased to 80° C. After 90 min, the resulting black mixture was poured into ice/water (300 mL) and diluted with 15percent i-PrOH/CHCl3 (200 mL). After slow addition of 6 N NaOH (80 mL, 15 mins), the aqueous layer was extracted with CHCl3 (2.x.80 mL). To the combined organic layers was added silica gel (30 g) and the solvent was then evaporated. The resulting solid was applied to a column of silica gel and eluted with 15-25percent EtOAc/hexanes to provide the product (5.0 g, 59percent, 2 steps): MS(ESI): 230 (M-H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | According to Scheme 10, the starting isatin (3.5 g, 15 mmol) and 6 N NaOH (25 mL, 10 equivalents) were heated at 80 C. and treated slowly with 30% H2O2 (4.5 mL, 0.3 mL/mmol, gas evolution). After 1 h, the mixture was cooled to room temperature and 6 N HCl was added dropwise (27 mL), whereupon a precipitate formed. After 30 mins, the mixture was cooled to 0 C. and the solid was filtered, washed with ice cold water (15 mL) and dissolved in CH2Cl2 (45 mL). The organic solution was dried (Na2SO4), filtered and evaporated to provide the product as an off-white solid (3.4 g, 88%): MS(ESI): 220 (M-H)-. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With sulfuric acid; at 60 - 80℃; | General procedure: Concentrated sulfuric acid (95 mL) was heated in a flask at 60 C. Intermediates 2 (12 g, 52mmol) were slowly added in portions to maintain the temperature below 70 C. The temperature was then increased to 80 C. After 3 h, the solution was cooled to room temperature, and then poured into crushed ice with vigorous stirring. The precipitate was collected by filtration and dried under vacuum to provide the product 3. |
70% | With sulfuric acid; at 55 - 80℃; for 0.166667h; | The procedure described by Marvel et al. (see Org. Synth. Coll. Vol. I, 327) was followed. Intermediate 12 (11.9 g, 48.5 mmol) was added in small portions to 35 mL of concentrated sulfuric acid at 55 C. in a 250 mL Erlenmeyer flask. The temperature of the solution was maintained below 70 C. until all the acetamide had been added and it was increased to 80 C. for 10 minutes. The dark-colored solution was cooled to room temperature and poured onto 175 mL of crushed ice. After standing for 30 minutes, the precipitate was collected by filtration, washed three times with water, and dried under vacuum to yield indoline-2,3-dione of sufficient purity to be used in the next step (intermediate 13, 8.32 g, 70% yield). 1H NMR (400 MHz, DMSO-d6) delta 7.15 (t, J=7.8 Hz, 1H), 7.56 (d, J=7.3 Hz, 1H), 7.64 (d, J=8.3 Hz, 1H), 11.71 (s, 1H). |
59% | According to Scheme 9, concentrated sulfuric acid (40 mL) was heated to 65 C. and poured into a flask containing the crude 2-(trifluoromethoxy)-alpha-oximinoanilide from Example 1.1. The mixture was stirred at 65 C. until homogeneous and then the temperature was increased to 80 C. After 90 min, the resulting black mixture was poured into ice/water (300 mL) and diluted with 15% i-PrOH/CHCl3 (200 mL). After slow addition of 6 N NaOH (80 mL, 15 mins), the aqueous layer was extracted with CHCl3 (2×80 mL). To the combined organic layers was added silica gel (30 g) and the solvent was then evaporated. The resulting solid was applied to a column of silica gel and eluted with 15-25% EtOAc/hexanes to provide the product (5.0 g, 59%, 2 steps): MS(ESI): 230 (M-H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4.5% | Intermediate 13 (1.00 g, 4.32 mmol) was taken up in 1 mL of ethanol and 3.4 mL of 10 M sodium hydroxide and the resulting mixture was heated at reflux temperature for 20 minutes. A solution of intermediate 55 in 7 mL of ethanol was added dropwise via syringe and the resulting mixture was heated overnight. It was cooled to room temperature and ethanol was removed under reduced pressure. The residue was diluted with water, acidified to pH 1 by slow addition of 1 M hydrochloric acid, and extracted with ethyl acetate. The combined ethyl acetate layers were concentrated to give a dark material which was purified by preparative HPLC (water/acetonitrile with 0.1% triethylamine). The purified triethylammonium salt was taken up in 20% acetonitrile in water and acidified with concentrated hydrochloric acid. Pure product precipitated out of solution as an off-white powder was collected to give Compound 1 (83 mg, 4.5% yield). 1H NMR (400 MHz, DMSO-d6) delta 1.35-1.39 (m, 2H), 1.49-1.54 (m, 2H), 7.16 (d, J=8.6 Hz, 2H), 7.28 (d, J=8.6 Hz, 2H), 7.57 (d, 1H), 7.62 (t, 1H), 8.69 (d, J=7.3 Hz, 1H). |
Tags: 149125-30-4 synthesis path| 149125-30-4 SDS| 149125-30-4 COA| 149125-30-4 purity| 149125-30-4 application| 149125-30-4 NMR| 149125-30-4 COA| 149125-30-4 structure
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P222 | Do not allow contact with air. |
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P272 | Contaminated work clothing should not be allowed out of the workplace. |
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P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
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P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
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P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
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P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
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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 |
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H226 | Flammable liquid and vapour |
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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 | |
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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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