Structure of 22864-65-9
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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. : | 22864-65-9 |
Formula : | C8H8F3N |
M.W : | 175.15 |
SMILES Code : | FC(C1=CC=C(C=C1)NC)(F)F |
MDL No. : | MFCD07369717 |
InChI Key : | UTUYWZJPVLDHJJ-UHFFFAOYSA-N |
Pubchem ID : | 15099755 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H317 |
Precautionary Statements: | P280 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 40.75 |
TPSA ? Topological Polar Surface Area: Calculated from |
12.03 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.9 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.67 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.71 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.88 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.51 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.73 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.85 |
Solubility | 0.25 mg/ml ; 0.00143 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.57 |
Solubility | 0.467 mg/ml ; 0.00266 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.72 |
Solubility | 0.0335 mg/ml ; 0.000191 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 |
-5.47 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 |
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) |
1.0 |
* 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 |
---|---|---|
65% | With thionyl chloride; triethylamine; In dichloromethane; | EXAMPLE 8 N-Methyl-N-(4-trifluoromethyl-phenyl)-1,2-dihydro-4-hydroxy-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide (Method B) To an ice-cold solution of 1,2-dihydro-4-hydroxy-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxylic acid (8 g, 0.032 mol), triethylamine (15.5 ml, 0.11 mol) and 4-trifluoromethyl-N-methylaniline (6.1 g, 0.035 mol) in 150 ml of methylene chloride was added dropwise during 0.5 hours a solution of thionyl chloride (3.0 ml, 0.042 mol) in 10 ml of methylene chloride. The stirring was continued at 4° C. for 4 hours. The solution was diluted with 10 ml of methylene chloride, washed with cold 1 M sulphuric acid and then extracted with 1 M sodium hydroxide. The pH of the aqueous phase was adjusted to 8-8.5, clarified by filtration and then acidified with hydrochloric acid to pH 4. On standing a crystalline precipitate was formed which was filtered off, washed with water and dried to give the title compound (8.5 g) yield 65percent. 1H NMR (CDCl3) delta 3.48 (3H, s), 3.54 (3H, s), 4.06 (3H, s), 6.70 (1H, d), 6.94 (1H, d), 7.46 (1H, t), 7.50 (4H, broad signal). 13C NMR (CDCl3) delta 29.8 (CH3), 36.9 (CH3), 56.9 (CH3), 103.5 (CH), 104.2 (C), 108.7 (CH), 109.5 (C), 117.3+121.7+126.0+130.3 (C), 125.8+125.9+125.9+126.0 (CH), 126.3 (CH), 127.9+128.4+128.9+129.4 (C), 131.8 (CH), 141.4 (C), 146.7 (C), 157.2 (C), 158.0 (C), 160.3 (C), 165.0 (C); some peaks are multiplets due to F-coupling. ESI MS/MS [M+H]+ 407, fragment 232. |
65% | With thionyl chloride; triethylamine; In dichloromethane; at 0 - 4℃; for 4.5h; | To an ice-cold solution of 1,2-dihydro-4-hydroxy-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxylic acid (8 g, 0.032 mol), triethylamine (15.5 ml, 0.11 mol) and 4-trifluoromethyl-N-methylaniline (6.1 g, 0.035 mol) in 150 ml of methylene chloride was added dropwise during 0.5 hours a solution of thionyl chloride (3.0 ml, 0.042 mol) in 10 ml of methylene chloride. The stirring was continued at 4°C for 4 hours. The solution was diluted with 10 ml of methylene chloride, washed with cold 1 M sulphuric acid and then extracted with 1 M sodium hydroxide. The pH of the aqueous phase was adjusted to 8-8.5, clarified by filtration and then acidified with hydrochloric acid to pH 4. On standing a crystalline precipitate was formed which was filtered off, washed with water and dried to give the title compound (8.5 g) yield 65 percent. 1H NMR (CDCl3) delta 3.48 (3H, s), 3.54 (3H, s), 4,06 (3H, s), 6.70 (1H, d), 6.94 (1H, d), 7.46 (1H, t), 7.50 (4H, broad signal). 13C NMR (CDCl3) delta 29.8 (CH3), 36.9 (CH3), 56.9 (CH3), 103.5 (CH), 104.2 (C), 108.7 (CH), 109.5 (C), 117.3+121.7+126.0+130.3 (C), 125.8+125.9+125.9+126.0 (CH), 126.3 (CH), 127.9+128.4+128.9+129.4 (C), 131.8 (CH), 141.4 (C), 146.7 (C), 157.2 (C), 158.0 (C), 160.3 (C), 165,0 (C); some peaks are multiplets due to F-coupling. ESI MS/MS [M+H]+ 407, fragment 232. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; | Example 212 N-Methyl-N-[5-(5,6-dimethoxy-3-methyl-1,4-benzoquinon-2-yl)methyl-2-acetoxybenzoyl]-4-trifluoromethylaniline N-Methyl-4-trifluoromethylaniline (0.200 g, 1.143 mmol), triethylamine (0.116 g, 1.143 mmol) and <strong>[37091-73-9]2-chloro-1,3-dimethylimidazolinium chloride</strong> (0.193 g, 1.143 mmol) were added to a methylene chloride solution (100 ml) of 5-(5,6-dimethoxy-3-methyl-1,4-benzoquinon-2-yl)methyl-2-acetoxybenzoic acid (0.285 g, 0.762 mmol) and the resulting solution was stirred at room temperature for 12 hours. The reaction solution was poured into ice water and then extracted with methylene chloride. The extract was washed with water and then dried, and the solvent was removed by distillation. The obtained residue was purified by preparative thin-layer chromatography (chloroform: methanol = 10:1) to obtain the titled compound (0.140 g, 0.263 mmol, 35percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | In octane; for 2.0h;Reflux; Molecular sieve;Product distribution / selectivity; | A mixture of 11 (5.00 g, 18.9 mmol), N-methyl-p-trifluoromethylaniline (5.13 g, 28.4 mmol) and n-octane (200 mL) were refluxed in a Soxhlet extraction apparatus containing 4A molecular sieves (22.9 g) for 2 hours. After cooling the mixture the product was isolated as above to furnish 7.6 g (99 percent) of 4-hydroxy-5-methoxy-N,l-dimethyl-2-oxo-N-[(4- trifluoromethyl)phenyl] - 1 ,2-dihydroquino line-3 -carboxamide (C) . 1 H-NMR analysis on the isolated product revealed no impurities other than 1 molpercent remaining ester 11. 1 H-NMR (CDCI3) 9.9 (s, 1H), 7.50 (bs, 4H), 7.46 (t, 1H), 6.94 (d, 1H), 6.70 (d, 1H), 4.06 (s, 3H), 3.54 (s, 3H), 3.48 (s, 3H). When the same reaction was performed by the traditional distillation from n-octane (Entry 26) during 2 hours according to prior art US patent No. 6,875,869 the product was isolated in 94 percent yield and determined by 1H-NMR analysis to consist of a mixture of compound C (96 molpercent) and the starting material 11 (4 molpercent). |
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