Structure of 886497-81-0
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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. : | 886497-81-0 |
Formula : | C8H4F4O2 |
M.W : | 208.11 |
SMILES Code : | FC1=C(C=O)C=C(OC(F)(F)F)C=C1 |
MDL No. : | MFCD04115886 |
InChI Key : | FMDGCHMPSCBYFX-UHFFFAOYSA-N |
Pubchem ID : | 2783324 |
GHS Pictogram: |
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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 | 0.12 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 6.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 38.47 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.92 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.25 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.22 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.01 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.99 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.88 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.3 |
Solubility | 0.105 mg/ml ; 0.000505 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.48 |
Solubility | 0.0695 mg/ml ; 0.000334 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.26 |
Solubility | 0.115 mg/ml ; 0.000552 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 |
-5.26 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) |
1.6 |
* 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 |
---|---|---|
88% | With hydroxylamine hydrochloride; sodium acetate; In ethanol; for 2h;Heating / reflux; | b) E-2-Fluoro-5-trifluoromethoxy-benzaldehyde oxime A solution of <strong>[886497-81-0]2-fluoro-5-trifluoromethoxy-benzaldehyde</strong> (9.78 g, 47 mmol) in ethanol (50 ml) was treated with hydroxylamine HCl (3.59 g, 52 mmol) and sodium acetate (4.27 g, 52 mmol). The mixture was refluxed for 2 h, the solvent was evaporated and the residue stirred with water (50 ml). The precipitate was filtered, dried and chromatographed (SiO2, heptanes:Ethyl acetate=100:0 to 80:2) and afforded the title compound (9.21 g, 88%) as a white solid. MS: m/e=223.0 [M]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | EXAMPLE 49 3-Trifluoromethoxy-10-methyl-9H-imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]benzodiazepine; a) 2-Fluoro-5-trifluoromethoxy-benzaldehyde; A solution of 1-fluoro-4-trifluoromethoxy-benzene (21.0 g, 117 mmol) in THF (233 ml) was cooled to <-70 C. Tert.-butyllithium (86 ml of a 1.5 molar solution in pentane, 129 mmol) was added at such a rate that temperature was kept <-70 C. Stirring in the dry ice bath was continued for 15 min, then DMF (11.6 ml, 150 mmol) was added dropwise keeping temperature <-70 C. After 30 min the reaction mixture was allowed to reach rt, quenched with saturated NH4Cl solution and extracted with ether. The organic phase was washed with brine, concentrated and chromatographed (SiO2, heptane:ethyl acetate=100:0 to 80:2). The title compound (11.0 g, 53%) was obtained as a light yellow oil. 1H-NMR (300 MHz, DMSO): delta=7.60 (t, J=9.2 Hz, 1H), 7.75-7.85 (m, 2H), 10.20 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1B [0232] To a solution of 2-bromopyridine (380 mg) in anhydrous tetrahydrofuran (3 mL) is slowly added a 1M solution of isopropylmagnesium bromide in tetrahydrofuran (2.64 mL) at room temperature. After stirring for 2 hours, <strong>[886497-81-0]2-fluoro-5-(trifluoromethoxy)benzaldehyde</strong> (0.50 mL) is added and the reaction mixture stirred for 2 hours. After hydrolysis with water and 3N hydrochloric acid, the mixture is washed with diethyl ether, basified with concentrated sodium hydroxide and extracted with ethyl acetate twice. The pooled organic extracts are dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography over silica gel (heptane/ethyl acetate 2/1) to afford (2-fluoro-5-trifluoromethoxyphenyl)pyridin-2-ylmethanol as an orange oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.38 g | With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 2h; | 12279] A mixture of 3.00 g of 2-fluoro-3-trifluoromethoxy- benzaldehyde, 1.33 g of methyl thioglycolate, 2.66 g ofpotassium carbonate, and 10 ml of N,N-dimethylformamide was stirred for 2 hours at 80 C. After the reaction mixture was cooled to room temperature, water was added thereto, and extraction was performed three times by using ethyl acetate. The collected organic layer was washed with water and saturated saline, dried over magnesium sulfate, and then concentrated under reduced pressure, thereby obtaining 1.38 g of methyl 5-trifluoromethoxybenzo[b]thiophene-2-carboxylate (hereinafier, described as a ?compound 98 of the present invention?).12280] Compound 98 of the Present Invention 12281] ?H-NMR(CDC13) oe: 8.05 (s, 1H), 7.87 (d, 1H, J=8.8Hz), 7.73 (d, 1H, J=1 .0Hz), 7.34 (dq, 1H, J=8.8, 1.0Hz), 3.96(s, 3H). |
1.38 g | With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 2h; | A mixture of 3.00 g of <strong>[886497-81-0]2-fluoro-5-trifluoromethoxybenzaldehyde</strong>, 1.33 g of methyl thioglycolate, 2.66 g of potassiumcarbonate, and 10 ml of N,N-dimethylformamide was stirred for 2 hours at 80C. After the reaction mixture wascooled to room temperature, water was added thereto, and extraction was performed three times by using ethyl acetate.The collected organic layer was washed with water and saturated saline, dried over magnesium sulfate, and thenconcentrated under reduced pressure, thereby obtaining 1.38 g of methyl 5-trifluoromethoxybenzo[b]thiophene-2-carboxylate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With titanium(IV)isopropoxide; In tetrahydrofuran; at 20℃; for 72h; | Titanium(IV) isopropoxide (5.69 mL, 19.22 mmol) was added to a THF (20 mL) solution of <strong>[886497-81-0]2-fluoro-5-(trifluoromethoxy)benzaldehyde</strong> (2.0 g, 9.61 mmol) and (S)-(10 )-2-methyl-2-propanesulfinamide (1.165 g, 9.61 mmol) at ft and stirred for 72 h. Thereaction mixture was quenched by adding brine (10 mL) and hexanes (10 mL) at 0 C.The mixture was filtered through a pad of celite, and the pad was rinsed with ethyl acetate(2 x 10 mL). The combined organic solutions were dried over sodium sulfate, filtered andconcentrated under reduced pressure to give crude product which was purified on a silicagel column with Hexanes/EtOAc (100/0 to 50/50) to give (S,E)-N-(2-fluoro-5-(trifluoromethoxy)benzylidene)-2-methylpropane-2-sulfinamide (2.827 g, 8.73 mmol, 91%yield).MS ESI m/z 312.0 (M+H) |
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