Structure of 306761-54-6
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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. : | 306761-54-6 |
Formula : | C10H12F3N |
M.W : | 203.20 |
SMILES Code : | CC(N)(C1=CC=C(C(F)(F)F)C=C1)C |
MDL No. : | MFCD09258816 |
InChI Key : | BZZQAWGDEQZOOF-UHFFFAOYSA-N |
Pubchem ID : | 22337579 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.4 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 48.61 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.02 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.28 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.39 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.94 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.19 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.82 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.93 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.79 |
Solubility | 0.329 mg/ml ; 0.00162 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.58 |
Solubility | 0.537 mg/ml ; 0.00264 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.75 |
Solubility | 0.0359 mg/ml ; 0.000177 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) |
Yes |
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 |
-5.84 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 |
1.0 |
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 |
0.0 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) |
1.19 |
* 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 |
---|---|---|
1.81 g | Reference Example 27-3 2-[4-(Trifluoromethyl)phenyl]propane-2-amine To a solution of 4-(trifluoromethyl)benzonitrile (3.01 g) in diethyl ether (88.0 mL), methylmagnesium bromide (about 3.0 mol/L, solution in diethyl ether, 17.6mL) was added and the mixture was stirred at room temperature for 40 minutes. To the reaction mixture, tetraisopropyl orthotitanate (5.15 mL) was added slowly and thereafter the mixture was refluxed for 6 hours. After cooling the mixture to 0C, an aqueous solution of 20% sodium hydroxide was added and the mixture was stirred at room temperature for an hour. After phase separation, the aqueous layer was extracted with diethyl ether twice. The combined organic layers were passed through a phase separator and thereafter concentrated under reduced pressure. The resulting residue was dissolved in 5% hydrochloric acid and washed with diethyl ether twice. The aqueous layer was rendered basic with an aqueous solution of 20% sodium hydroxide and extracted with diethyl ether three times. The combined organic layers were washed with saturated brine and thereafter passed through a phase separator to be concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 95:5-10:90) to give the titled compound as a yellow oil (1.81 g). 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.51 (s, 6 H) 7.54 - 7.69 (m, 4 H). MS ESI/APCI Dual posi: 204[M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | In toluene; acetonitrile; for 24h;Heating / reflux; | Preparation of 3-[2-(4-trifluoromethylphenyl)-2-propylamino]-1-propanesulfonic acid A mixture of <strong>[306761-54-6]1-(4-trifluoromethylphenyl)-1-methylethylamine</strong> (8.30 mmol, 1.69 g), 1,3-propane sultone (8.5 mmol, 0.75 mL), MeCN (7 mL) and toluene (3 mL) was heated to reflux for 24 hours. After cooling to room temperature, the solid was collected by filtration, rinsed with ethanol (3*5 mL) and dried for 1 hour at 60 C. in a vacuum oven (2.47 g). The solid obtained was suspended in 95% ethanol (20 mL) and the mixture was heated to reflux for 1 hour. After cooling to room temperature, the solid was collected by filtration, rinsed with ethanol (2*5 mL) and dried for 2 hours at 60 C. in a vacuum oven. The desired material was obtained as a white solid (2.39 g, 89%). 1H NMR (300 MHz, DMSO-d6) δ 1.69 (s, 6H), 1.94 (qt, J=6.4 Hz, 2H), 2.60 (t, J=6.4 Hz, 2H), 2.79 (br s, 2H), (q, J=8.5 Hz, 4H), 9.32 (br s, 2H); 13C (75 MHz, DMSO-d6) δ 22.25, 25.15, 41.97, 49.26, 59.93, 123.70 (q, J=271 Hz), 125.52 (d, J=3.5 Hz), 126.89, 128.71 (q, J=31.9 Hz)143.84; 19F (282 MHz, DMSO-d6) -61.87 (s); ES-MS 324 (M-1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
957 mg | In methanol; water; at 90℃; for 1h;Microwave irradiation; | Reference Example B-1 Ethyl N-{2-[4-(trifluoromethyl)phenyl]propan-2-yl}-β-alaninate To a mixture of the compound (1.11g) obtained in Reference Example 27-3, methanol (6.00 mL) and water (3.00 mL), ethyl acrylate (0.594 mL) was added and the resulting mixture was stirred at 90C for an hour under irradiation with microwaves. After being cooled to room temperature, the reaction mixture was poured into water and extracted with ethyl acetate three times. The combined organic layers were washed with saturated brine and thereafter passed through a phase separator for concentrating under reduced pressure. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 95:5-10:90) to give the titled compound as a pale yellow oil (957 mg). 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.26 (t, J=7.1 Hz, 3 H) 1.47 (s, 6 H) 2.39-2.49 (m, 2 H) 2.53 - 2.61 (m, 2 H) 4.14 (q, J=7.1 Hz, 2 H) 7.58 (s, 4 H). MS ESI/APCI Dual posi: 304[M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step A: Anhydrous CeCl3 (0.84 g, 3.4 mmol) was stirred in dry THF (10 mL), at room temperature, under a N2 atmosphere for 2 h. Then, the solution was cooled at -78 C, followed by dropwise addition of MeLi (2.2 mL, 3.4 mmol, 1.6 M), and allowed to stir for 30 min at -78 C. Then, a solution of 4-methoxybenzonitrile (0.15 g, 1.1 mmol) in dry THF (5 mL) was added dropwise to the above solution. The crude reaction was stirred at room temperature overnight, quenched by adding 1.5 mL of concentrated NH4OH, and allowed to stir for 1 h at room temperature. The organic layer was filtered, dried over anhydrous Na2SO4, and concentrated in vacuo. The crude product was used for next reaction without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; at 20℃;Inert atmosphere; | General procedure: Step B The crude from above (0.16 g, 0.97 mmol) was dissolved in dry DCM (5 mL) and a solution of 5-nitro-2-furoyl chloride (0.17 g, 0.97 mmol) in dry DCM (5 mL) was added dropwise, followed by dropwise addition of Et3N (0.27 mL, 1.9 mmol) at room temperature. The crude reaction was stirred at room temperature until reaction completion, diluted with DCM (10 mL), and washed with saturated aqueous brine solution (15 mL). The organic layer was separated, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. Product was purified by column chromatography (95% DCM: 5% MeOH). |
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