Structure of 89763-93-9
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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. : | 89763-93-9 |
Formula : | C8H4F4O |
M.W : | 192.11 |
SMILES Code : | O=CC1=CC=C(C(F)(F)F)C=C1F |
MDL No. : | MFCD00061310 |
Boiling Point : | No data available |
InChI Key : | KFEHNXLFIGPWNB-UHFFFAOYSA-N |
Pubchem ID : | 522929 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 36.79 |
TPSA ? Topological Polar Surface Area: Calculated from |
17.07 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.74 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.37 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.23 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.94 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.43 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.94 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.73 |
Solubility | 0.355 mg/ml ; 0.00185 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.37 |
Solubility | 0.821 mg/ml ; 0.00428 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.51 |
Solubility | 0.0588 mg/ml ; 0.000306 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 |
-5.79 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) |
1.46 |
* 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 |
---|---|---|
20% | With potassium carbonate; In dimethyl sulfoxide; at 80℃;Inert atmosphere; | A round-bottom flask was charged with 2-fluoro-4-(trifluoromethyl)benzaldehyde (1.00 g, 5.21 mmol, 1.00 equiv), potassium carbonate (2.16 g, 15.6 mmol, 3.00 equiv), <strong>[138007-24-6]ter<strong>[138007-24-6]t-butyl piperidine-4-carboxylate</strong></strong> (1.93 g, 10.4 mmol, 2.00 equiv), and dimethyl sulfoxide (20 mL) under nitrogen. The reaction mixture was stirred overnight at 80 °C and quenched with water (20 mL). The resulting solution was extracted with ethyl acetate (3 x 20 mL) and the organic layers were combined, washed with brine (2 x 20 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on a silica gel column to provide 380 mg (20percent yield) of tert-butyl 1-(2-formyl-5-(trifluoromethyl)phenyl)piperidine-4- carboxylate. LCMS (ESI, m/z): 358 [M+Hj. |
4.61 g | With potassium carbonate; In 1-methyl-pyrrolidin-2-one; at 80℃; for 19h; | (1) A suspension of Compound 1 (3.05 g), Compound 2 (3.25 g), and potassium carbonate (3.3 g) in N-methylpyrrolidone (40 mL) was stirred at 80°C for 19 hours. The reaction mixture was cooled to room temperature, water and ethyl acetate were added thereto, stirred, and then extracted with ethyl acetate. The resultant organic layer was washed with water and saturated saline, dried, and concentrated under reduced pressure. The residue was purified with silica gel column chromatography (hexane:ethyl acetate=98:2-88:12) to give Compound 3 (4.61 g) as a yellow viscous material. MS (ESI): m/z 358 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | A flask was charged with <strong>[33689-29-1]methyl 1-hydroxycyclopropane-1-carboxylate</strong> (362 mg, 3.12 mmol, 1.50 equiv) and THF (10 mL). Sodium hydride (125 mg, 3.12 mmol, 1.50 equiv, 60% in mineral oil) was added at 0 C. The mixture was stirred for 20 min at rt before 2-fluoro-4-(trifluoromethyl)benzaldehyde (400 mg, 2.08 mmol, 1.00 equiv) was added. The resulting solution was stirred for 1 h at rt and quenched with water (30 mL). The resulting solution was extracted with DCM (2*50 mL) and the organic layers were combined, washed with brine (2*30 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The residue was chromatographed on a silica gel column with EtOAc/petroleum ether (1/10) to provide 180 mg (29% yield) of methyl 1-(2-formyl-5-(trifluoromethyl)phenoxy)cyclopropane-1-carboxylate as a light yellow oil. | |
24% | A flask was charged with methyl 1 -hydroxycyclopropane- 1 -carboxylate (1.36 g,11.7 mmol, 1.50 equiv) and THF (10 mL). Sodium hydride (0.780 g, 19.5 mmol, 2.50 equiv, 60% in mineral oil) was added at 0 C. The mixture was stirred for 20 mm at room temperature. 2-Fluoro-4-(trifluoromethyl)benzaldehyde (1.50 g, 7.81 mmol, 1.00 equiv) was added. The resulting solution was stirred for 1 h at room temperature and quenched with water (30 mL). The resulting solution was extracted with DCM (2 x 50 mL) and the organic layers were combined, washed with brine (2 x 30 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on a silica gel column to provide 530 mg (24% yield) of methyl 1-(2-formyl-5- (trifluoromethyl)phenoxy)cyclopropane-1-carboxylate as a yellow oil. ?H NMR (300 IVIHz, Chloroform-cl) oe 10.50 (s, 1H), 8.00 - 7.97 (m, 1H), 7.38 - 7.27 (m, 2H), 3.79 (s, 3H), 1.82 - 1.70 (m, 2H), 1.52 - 1.44 (m, 2H). |
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