Structure of 447-61-0
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 447-61-0 |
Formula : | C8H5F3O |
M.W : | 174.12 |
SMILES Code : | C1=CC=CC(=C1C=O)C(F)(F)F |
MDL No. : | MFCD00003337 |
InChI Key : | ZDVRPKUWYQVVDX-UHFFFAOYSA-N |
Pubchem ID : | 123067 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 36.83 |
TPSA ? Topological Polar Surface Area: Calculated from |
17.07 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.67 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.78 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.67 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.52 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.98 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.72 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.91 |
Solubility | 0.215 mg/ml ; 0.00123 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.79 |
Solubility | 0.279 mg/ml ; 0.00161 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.23 |
Solubility | 0.103 mg/ml ; 0.000592 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 |
-5.39 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) |
1.1 |
* 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 |
---|---|---|
With toluene-4-sulfonic acid; In toluene; for 24h;Heating / reflux; | 3 (S)-Pyrrolidin-3-amine (0.45g, 5.2mmol) and trifluoromethylbenzaldehyde (0.87g, 5. 0MMOL), a crystal of 4-toluenesulphonic acid and toluene were refluxed with stirring for one day, using a Dean and Stark apparatus. The solution was evaporated in vacuo to give the title compound as a brown oil (M+H = 243). | |
With toluene-4-sulfonic acid; toluene; for 24h;Heating / reflux; | 3 (S)-PYRROLIDIN-3-AMINE (0.45g, 5.2mmol) and trifluoromethylbenzaldehyde (0. 87G, 5. 0MMOL), a crystal of 4-toluenesulphonic acid and toluene were refluxed with stirring for one day, using a Dean and Stark apparatus. The solution was evaporated in vacuo to give the title compound as a brown oil (M+H = 243). | |
With toluene-4-sulfonic acid; In toluene; for 24h;Heating / reflux; | 3 (S)-PYRROLIDIN-3-AMINE (0.45g, 5.2mmol) and TRIFLUOROMETHYLBENZALDEHYDE (0.87g, 5. 0MMOL), a crystal of 4-toluenesulphonic acid and toluene were refluxed with stirring for one day, using a Dean and Stark apparatus. The solution was evaporated in vacuo to give the title compound as a brown oil (M+H = 243). |
With toluene-4-sulfonic acid; In toluene; for 24h;Heating / reflux; | 3 (S)-Pyrrolidin-3-amine (0.45g, 5. 2mmol) and trifluoromethylbenzaldehyde (0.87g, 5. 0mmol), a crystal of 4-toluenesulphonic acid and toluene were refluxed with stirring for one day, using a Dean and Stark apparatus. The solution was evaporated in vacuo to give the title compound as a brown oil (M+H = 243). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen;5%-palladium/activated carbon; In ethanol; under 3102.97 Torr; for 3h; | A mixture of 3 (S)-pyrrolidin-3-amine (4g, 46. 5mmol), 2-trifluoromethylbenzaldehyde (9. 1g, 46. 5mmol), 5% palladium on carbon (0.4g) and ethanol (150mL) was hydrogenated at 60psi for 3 hours using a Parr hydrogenator. The catalyst was filtered off and the filtrate evaporated in vacuo to give the title compound as an oil. MS: [M+H] = 245. | |
With hydrogen;5%-palladium/activated carbon; In ethanol; under 3102.97 Torr; for 3h; | A mixture of 3 (S)-pyrrolidin-3-amine (4g, 46. 5MMOL), 2-trifluoromethylbenzaldehyde (9. 1g, 46. 5MMOL), 5% palladium on carbon (0.4g) and ethanol (150ML) was hydrogenated at 60psi for 3 hours using a Parr hydrogenator. The catalyst was filtered off and the filtrate evaporated in vacuo to give the title compound as an oil. MS: [M+H] = 245. | |
With hydrogen;5%-palladium/activated carbon; In ethanol; under 3102.97 Torr; for 3h; | A mixture of 3(S)-pyrrolidin-3-amine (4g, 46. 5MMOL), 2-trifluoromethylbenzaldehyde (9. 1g, 46. 5MMOL), 5% palladium on carbon (0.4g) and ethanol (150mL) was hydrogenated at 60psi for 3 hours using a Parr hydrogenator. The catalyst was filtered off and the filtrate evaporated in vacuo to give the title compound as an oil. MS: [M+H] = 245. |
With hydrogen;palladium on activated carbon; In ethanol; under 3102.97 Torr; for 3h; | A mixture of 3(S)-pyrrolidin-3-amine (4g, 46. 5MMOL), 2-trifluoromethylbenzaldehyde (9. 1g, 46. 5MMOL), 5% palladium on carbon (0.4g) and ethanol (150mL) was hydrogenated at 60psi for 3 hours using a Parr hydrogenator. The catalyst was filtered off and the filtrate evaporated in vacuo to give the title compound as an oil. MS: [M+H] = 245. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium ethanolate; In ethanol; at 20℃; | General procedure: Various aldehydes (1.0 equiv) were added to stirred solutions of indolin-2-one, 5-chloroindolin-2-one or <strong>[5654-97-7]7-azaoxindole</strong> (1.0equiv) in absolute ethanol. After stirring at room temperature for 5 min NaOEt/EtOH (0.5 mL) was added and the mixture was then stirred at room temperature overnight. The solvent was then removed under vacuum. The residue was washed with saturated sodium chloride solution and then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under vacuum. The solid part was purified by chromatography over silica gel using ethyl acetate/petroleum ether as the eluent to afford desired compounds 1a-1g, 2a, 3a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | General procedure: A solution of lithium hydroxide (0.8 mg, 0.03 mmol) and 2'-methoxyacetophenone (26 mg, 0.157 mmol) in absolute methanol (1.5 mL) was stirred at room temperature for 15 min. To the resulting mixture was added a solution of 2-(trifluoromethyl)-3-pyridinecarboxaldehyde (6a, 28 mg, 0.16 mmol) in absolute methanol (15 mL). The reaction was stirred overnight at room temperature (approx. 18 h). The reaction was then concentrated on a rotary evaporator and the resulting oily residue purified by chromatography on silica gel using a gradient of 0-100% ethyl acetate in hexane to provide the desired product (17 mg, 35%) as a light yellow waxy solid. Prepared using the general method from lithium hydroxide (1 mg, 0.04 mmol), 2-(trifluoromethyl)benzaldehyde (34 mg, 0.2 mmol) and <strong>[131674-40-3]1-(2-methoxypyridin-3-yl)ethanone</strong> (7d, 29 mg, 0.19 mmol) in absolute methanol (final reaction volume = 1.5 mL). The reaction mixture was purified by chromatography on silica gel (40% ethyl acetate in hexane) to give the desired product as a yellow solid (29 mg, 49%). 1H NMR (CDCl3) delta 8.36 (dd, J = 4.8, 2.0 Hz, 1H), 8.08 (dd, J = 7.4, 2.0 Hz, 1H), 8.05 (dd, J = 15.6, 2.2 Hz, 1H), 7.83 (d, J = 7.8 Hz, 1H), 7.75 (d, J = 7.8 Hz, 1H), 7.63 (t, J = 7.6 Hz, 1H), 7.53 (d, J = 7.5 Hz, 1H), 7.47 (d, J = 15.7 Hz, 1H), 7.05 (dd, J = 7.4, 4.8 Hz, 1H), 4.09 (s, 3H). 13C NMR (CDCl3) delta 189.3, 160.6, 149.5, 138.9, 137.9, 135.9, 131.0, 130.1, 129.8, 128.6, 126.9, 125.2, 124.5, 121.2, 116.1, 52.8. HRMS (FAB): calcd C16H12F3NO2 + H = 308.0898, found 308.0874. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40.8% | With sodium methylate; In methanol; at 60℃; | Using the method of synthesizing an intermediate similar to that of Example 1,Take 0.01 mol of <strong>[13338-63-1]3,4,5-trimethoxyphenylacetonitrile</strong> (5), 0.01 mol of 2-trifluoromethylbromobenzaldehyde and 20 mL of methanol into a 50 mL three-necked flask.Stirring to 60 C, adding 0.005 mol of sodium methoxide, constant temperature reaction 4-6 h,TLC scanning and detection, after the reaction is completed, it is cooled to room temperature, filtered, washed with water, dried, and recrystallized from methanol to obtain a pale yellow solid. Yield: 40.8%, |
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