Structure of 159981-19-8
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CAS No. : | 159981-19-8 |
Formula : | C8H6F3NO2 |
M.W : | 205.13 |
SMILES Code : | O=CC1=CC=C(OCC(F)(F)F)N=C1 |
MDL No. : | MFCD06738679 |
InChI Key : | XKOBNYABZGUMQN-UHFFFAOYSA-N |
Pubchem ID : | 21698499 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 6.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 41.11 |
TPSA ? Topological Polar Surface Area: Calculated from |
39.19 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.73 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.73 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.1 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.73 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.4 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.94 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.25 |
Solubility | 1.14 mg/ml ; 0.00556 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.17 |
Solubility | 1.39 mg/ml ; 0.00677 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.01 |
Solubility | 0.2 mg/ml ; 0.000975 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 |
-6.32 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) |
1.71 |
* 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 |
---|---|---|
287 mg | With diisobutylaluminium hydride In toluene at -78℃; for 1 h; Inert atmosphere | General procedure: (2) Diisobutylaluminum hydride (toluene solution, 1.01 mol/L, 1.95 mL, 1.97 mmol) was added dropwise to a solution of N-methoxy-N-methyl-6-(2,2,2-trifluoroethoxy)pyridine-3-carboxamide obtained (432 mg, 1.64 mmol) in toluene (11 mL) at -78°C under a nitrogen atmosphere. The mixture was stirred at the same temperature for 1 hr. Methanol (5 mL) was added dropwise to the reaction mixture, the mixture was warmed to room temperature, and 50percent aqueous Rochelle salt solution (10 mL) was added thereto, followed by stirring for 1.5 hr. The mixture was extracted with chloroform and the organic layer was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate = 9:1 → 7:3) to afford the title compound as a colorless solid (287 mg). 1H NMR (300 MHz, CDCl3) δ ppm 4.86 (q, J = 8.4 Hz, 2 H), 6.97 - 7.02 (m, 1 H), 8.16 (dd, J = 8.6, 2.3 Hz, 1 H), 8.62 - 8.66 (m, 1 H), 10.00 (d, J = 0.6 Hz, 1 H). LCMS retention time: 1.86 min. (Condition 3) MS ESI/APCI Dual posi: 206[M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step 1 - Synthesis of[5-(5-chloro-lH-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-[6-(2,2,2- trifluoro-ethoxy)-pyridin-3-ylmethyl]-amine (P-0409):; [0254] To 5-(l -benzenesulfonyl-5-chloro-lH-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2- ylamine (599, 124.1 mg, 0.31 mmol, prepared as described in Example 29, Scheme 185) in ethanol (3.00 mL) and acetic acid (0.2 mL) were added 6-(2,2,2-trifluoro-ethoxy)-pyridine-3- carbaldehyde (603, 164.0 mg, 0.80 mmol) and silica supported cyanoborohydride (1.21 mmol/g, 0.700 g). The reaction was irradiated with microwave on 300 watts, 1000C for 150 minutes. To the reaction was added a solution of potassium hydroxide (9.0 M in water, 1.0 mL). The reaction was irradiated with microwave on 300 watts, 100 0C for 10 minutes. The reaction was poured into aqueous potassium carbonate and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 20% to 100% ethyl acetate in hexane to give the desired compound (P-0409, 10.6 mg, 7.6%). MS ESI) [M+H+]+ = 448.4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With manganese(IV) oxide; In acetonitrile; for 24h; | General procedure: To a solution of (4-chloro-2-fluorophenyl)methanol (222mg) in MeCN (20ml) was added Mn02 (480mg). The mixture was stirred for 24h. The mixture was filtered over celite, the org. layer was dried over MgS04 and evaporated in vacuo. The crude aldehyde was used without purification in the next step. LC-MS (A): tR = 0.76min; [M+H]+: not visible. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | n-Butyllithium (5.14 mL, 13.4 mmol) is added to a suspension of methyltriphenylphosphonium bromide (4.41 g, 12.34 mmol) in tetrahydrofuran (51 mL) at -78 oC under nitrogen atmosphere . The reaction mixture is warmed to room temperature to yield deep red ylide solution. To ylide solution, cooling in ice, is introduced <strong>[159981-19-8]6-(2,2,2-trifluoroethoxy)nicotinaldehyde</strong> (2.11 g, 10.3 mmol, Step-1) in tetrahydrofuran (10 mL) and stirred at room temperature for 3 hours. The reaction mixture is poured into water, extracted with ethyl acetate and dried over sodium sulfate and concentrated in vacuo. The residue is purified by column chromatography on silica gel eluting with n-hexane / ethyl acetate (10:1) to give 1.56 g (75% yield) of the title compound as colorless oil.1H-NMR (300 MHz, CDCl3) delta 8.10 (1H, d, J = 2.6 Hz), 7.75 (1H, dd, J = 8.4, 2.6 Hz), 6.84 (1H, d, J = 8.4 Hz), 6.65 (1H, dd, J = 17.6, 11.0 Hz), 5.68 (1H, d, J = 17.6 Hz), 5.27 (1H, d, J = 11.0 Hz), 4.76 (2H, q, J = 8.4 Hz), MS (ESI) m/z: 204 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
287 mg | With diisobutylaluminium hydride; In toluene; at -78℃; for 1h;Inert atmosphere; | General procedure: (2) Diisobutylaluminum hydride (toluene solution, 1.01 mol/L, 1.95 mL, 1.97 mmol) was added dropwise to a solution of N-methoxy-N-methyl-6-(2,2,2-trifluoroethoxy)pyridine-3-carboxamide obtained (432 mg, 1.64 mmol) in toluene (11 mL) at -78C under a nitrogen atmosphere. The mixture was stirred at the same temperature for 1 hr. Methanol (5 mL) was added dropwise to the reaction mixture, the mixture was warmed to room temperature, and 50% aqueous Rochelle salt solution (10 mL) was added thereto, followed by stirring for 1.5 hr. The mixture was extracted with chloroform and the organic layer was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate = 9:1 ? 7:3) to afford the title compound as a colorless solid (287 mg). 1H NMR (300 MHz, CDCl3) delta ppm 4.86 (q, J = 8.4 Hz, 2 H), 6.97 - 7.02 (m, 1 H), 8.16 (dd, J = 8.6, 2.3 Hz, 1 H), 8.62 - 8.66 (m, 1 H), 10.00 (d, J = 0.6 Hz, 1 H). LCMS retention time: 1.86 min. (Condition 3) MS ESI/APCI Dual posi: 206[M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic acid; In methanol; at 40℃; | Resin-bound tetra-alkylcyanoborohydride (9.03 g, 21.2 mmol) was added to a preformed mixture of 7-(benzylthio)-1,2,3,4-tetrahydroisoquinoline (4 g, 14.1 mmol), <strong>[159981-19-8]6-(2,2,2-trifluoroethoxy)nicotinaldehyde</strong> (3.18 g, 15.5 mmol), and glacial acetic acid (3.23 ml, 56.4 mmol) in MeOH (35 ml). The reaction vessel was fitted with a reflux condensor and heated to 40 C. overnight. The reaction mixture was cooled to room temperature, filtered through a fritted funnel, then neutralized by the addition of saturated aqueous NaHCO3 solution. The layers were cut and the aqueous phase extracted with EtOAc×3. The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by medium pressure liquid chromatography ?MPLC? (KP-Sil 100 g SNAP column, BIOTAGE system) eluting with 1% MeOH/DCM over 3 CV followed by a gradient of 6-9% MeOH/DCM over 8 CV to give the desired compound. LC/MS (m/z): 445 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With manganese(IV) oxide; In dichloromethane; at 20℃; for 16h; | To a solution of [6-(2,2,2-trifluoro-ethoxy)-pyridin-3-yl]-methanol (2.7 g) in DCM (150 mL) was added MnO2 (16.9 g). After stirring for 16 hours at RT, the mixture was filtered through a pad of Celite. The filtrate was concentrated in vacuo to provide 6-(2,2,2-trifluoro-ethoxy)-pyridine-3-carbaldehyde. MS ESI+: m/z=206 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a suspension of NaH (2.0 g) in THF (100 mL) was added a mixture of 1-acetyl-pyrrolidin-2-one (1.6 g), <strong>[159981-19-8]6-(2,2,2-trifluoro-ethoxy)-pyridine-3-carbaldehyde</strong> (2.6 g) and THF (5 mL) dropwise at ice-bath temperature. After the addition was complete, the reaction mixture was stirred for 10 min at ice-bath temperature. Acetic acid (5 mL) was slowly added dropwise to destroy the excess NaH. The reaction mixture was poured into ice-water and extracted with EA (100 mL*2). The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by SGC (DCM/MeOH=20:1) to provide 3-[1-[6-(2,2,2-trifluoro-ethoxy)-pyridin-3-yl]-meth-(E)-ylidene]-pyrrolidin-2-one. MS ESI+: m/z=273 [M+H]+. |
Tags: 159981-19-8 synthesis path| 159981-19-8 SDS| 159981-19-8 COA| 159981-19-8 purity| 159981-19-8 application| 159981-19-8 NMR| 159981-19-8 COA| 159981-19-8 structure
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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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