Structure of 924818-17-7
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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. : | 924818-17-7 |
Formula : | C5H2BrF3S |
M.W : | 231.03 |
SMILES Code : | FC(F)(F)C1SC=CC=1Br |
MDL No. : | MFCD08437595 |
InChI Key : | WAEYJGSTKDPCSW-UHFFFAOYSA-N |
Pubchem ID : | 26596534 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H320-H335 |
Precautionary Statements: | P261-P280-P301+P312-P302+P352-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.2 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 37.02 |
TPSA ? Topological Polar Surface Area: Calculated from |
28.24 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.19 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.21 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.68 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.13 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
4.26 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.5 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.6 |
Solubility | 0.0582 mg/ml ; 0.000252 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.48 |
Solubility | 0.0773 mg/ml ; 0.000335 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 |
-5.43 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) |
2.38 |
* 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 |
---|---|---|
Description 5; 4-Bromo-5-(trifluoromethyl)-2-thiophenecarboxylic acid (D5); Diisopropylamine (2.1 ml, 14.9mmol, 1.1 equivalents) in dry tetrahydrofuran (60ml) under argon was cooled to -65C (internal temperature) and 2.5M n-butyllithium in hexanes (5.95ml, 14.9mmol, 1.1 equivalents) was added cautiously. The solution was allowed to warm to 00C, after 20 minutes it was cooled to -400C and treated slowly with 3-bromo-2-trifluoromethylthiophene (3.13g, 13.5mmol, 1 equivalent) in tetrahydrofuran (10ml). After stirring at -40C for 20 minutes, the solution was allowed to warm to -100C for 5 minutes and then re-cooled to -400C. Carbon dioxide was bubbled through the reaction mixture and the reaction allowed to warm to +5C. The solvent was removed in vacuo, the residue treated with water (20ml) then acidified to pH1 by the addition of aqueous 2M hydrochloric acid. The mixture was extracted with 4 times ethyl acetate (70ml), and then combined, dried over sodium sulphate and concentrated in vacuo to give 4-bromo-5-(trifluoromethyl)-2- thiophenecarboxylic acid (2.69g) as a dark solid. 1H-NMR (CDCI3, 400MHz): δ 7.80 (1 H, q). MS: m/z (M+H)+ 275, C6H2BrF3O2S requires 275. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | To a solution of N,N-diisopropylamine (680 μ, 5.19 mmol) in tetrahydrofuran (5 ml) was added dropwise a solution of 1.67 mol/L rc-butyllithium in hexane (3.1 1 ml, 5.19 mmol) at -78C under argon atmosphere, and the mixture was stirred at the same temperature for 15 minutes. The reaction solution was slowly warmed to 0C, and stirred for 20 minutes, and then cooled to -40C. Then, thereto was added dropwise a solution of 3-bromo-2- (trifluoromethyl)thiophene (1000 mg, 4.33 mmol) in tetrahydrofuran (15 ml). The mixture was stirred at the same temperature for 20 minutes, and the reaction solution was slowly warmed to -10C, and then stirred for 5 minutes. The reaction solution was cooled to -40C, and then thereto was added dropwise N,N-dimethylformamide (1 mL). Then, the mixture was slowly warmed to 0C, and stirred overnight. To the reaction solution was added water, and the mixture was extracted with ethyl acetate twice. The organic layer was combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate = 10:0-→9: 1) to give 4-bromo-5-(trifluoromethyl)thiophene-2- carbaldehyde (527 mg, 47%) as a yellow oil.'H-NMR (CDC13) δ 7.71 (1H, m), 9.93 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | Reference Synthesis Example 102 (0736) [4-Bromo-5-(trifluoromethyl)thiophen-2-yl]methanol (0737) To a tetrahydrofuran solution (5.0 mL) of <strong>[924818-17-7]3-bromo-2-(trifluoromethyl)thiophene</strong> (500 μL, 2.08 mmol), lithium diisopropylamide (2.06 mL, 2.29 mmol) was added under nitrogen atmosphere at -40 C., and the resultant mixture was stirred for 30 minutes. To the reaction solution, paraformaldehyde (68.8 mg, 2.29 mmol) was added and the resultant mixture was stirred for 30 minutes, followed by raising the temperature of the mixture to -10 C. The mixture was stirred at -10 C. for 4 hours and at 0 C. for 1 hour. After completion of the reaction, a 1 M hydrochloric acid was added to the reaction solution and extraction from the resultant mixture with ethyl acetate was performed. The organic layer was washed with a saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (106 mg, yield 20%). |
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