Structure of 261723-32-4
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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. : | 261723-32-4 |
Formula : | C7H6BrFO |
M.W : | 205.02 |
SMILES Code : | OCC1=C(F)C(Br)=CC=C1 |
MDL No. : | MFCD09842441 |
Boiling Point : | No data available |
InChI Key : | LIZLYZVAYZQVPG-UHFFFAOYSA-N |
Pubchem ID : | 26985646 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 40.23 |
TPSA ? Topological Polar Surface Area: Calculated from |
20.23 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.02 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.83 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.35 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.72 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.77 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.34 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.64 |
Solubility | 0.467 mg/ml ; 0.00228 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.88 |
Solubility | 2.73 mg/ml ; 0.0133 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.36 |
Solubility | 0.0887 mg/ml ; 0.000433 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 |
-6.25 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) |
1.38 |
* 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 |
---|---|---|
97% | With borane-THF; In tetrahydrofuran; for 5h;Cooling with ice; | Dissolve <strong>[161957-56-8]3-bromo-2-fluorobenzoic acid</strong> (25g) in tetrahydrofuran (50mL),Slowly add borane tetrahydrofuran solution (1mol/L, 17mL) under ice bath,After reacting for about 5 hours, the reaction was stopped and quenched by adding water (50 mL).Extract with ethyl acetate (30mL x 3), combine the organic phases, wash with 1N HCl (30 mL x 2), dry over anhydrous sodium sulfate and evaporate the solvent under reduced pressure.Obtain yellow oily compound A1-1 (22.7g) |
With borane-THF; In tetrahydrofuran; at 20℃; | 5.0 g of <strong>[161957-56-8]3-bromo-2-fluorobenzoic acid</strong> and 40 ml_ of anhydrous tetrahydrofuran were placed under nitrogen in an oven-dried flask and chilled to 00C. 34.2 ml_ of 1 M boran-tetrahydrofuran complex was added from an addition funnel, and the mixture was stirred at room temperature overnight. 5 ml_ of water were added, and the reaction was concentrated, diluted with diethyl ether, and extracted with saturated potassium carbonate, water, and 5% sodium chloride before drying over sodium sulfate. The solution was <n="88"/>filtered, concentrated, and purified by flash chromatography on silica. The product fractions were concentrated and vacuum dried to give 4.26 g. GCMS (M) 204; 1 H NMR (400 MHz, DMSO-c/6) δ ppm 4.57 (d, J=5.91 Hz, 2 H) 5.39 (t, J=5.77 Hz, 1 H) 7.15 (t, J=8.06 Hz, 1 H) 7.44 - 7.50 (m, 1 H) 7.55 - 7.61 (m, 1 H). | |
With borane-THF; In tetrahydrofuran; at 0 - 20℃; | A cooled (0 0C) solution of <strong>[161957-56-8]3-bromo-2-fluorobenzoic acid</strong> (Fluorochem; 500 mg; 2.28 mmol) in anhydrous THF (4 ml.) was slowly treated with borane-tetrahydrofuran complex (3.42 ml 1.00 M; 3.42 mmol) and the resulting solution was stirred at RT for 2 days. Borane-tetrahydrofuran complex (3.42 ml 1.00 M; 3.42 mmol) was added and the reaction mixture was stirred at RT for a further 3 hours. The reaction was carefully quenched with water and the mixture was concentrated. The residue was dissolved in Et2O, and the aqueous phase was saturated with K2CO3. The organic layer was separated and the aqueous phase was extracted with Et2O. The combined organic phases were washed with water and brine, dried over MgSO4 and concentrated to dryness affording the title compound as a colorless oil.1H NMR (300MHz, DMSO-d6) δ [ppm] 7.60 (1 H, m), 7.45 (1 H, m), 7.15 (1 H, t, J= 7.1 Hz), 5.42 (1 H, s), 4.57 (2H, s). HPLC (Condition A): Rt 2.67 min (HPLC purity 97.6%). |
With borane-THF; In tetrahydrofuran; at 20℃;Cooling with ice; | To an ice-cold solution of Compound I (2.5 g) in THF (23 mL) was added borane.THF complex (17 mL, 1.0 M THF solution), and the resulting mixture was stirred at room temperature overnight. To the ice-cold reaction mixture was added water, and the mixture was concentrated under reduced pressure. The residue was diluted with water, and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=4/1) to give Compound II (2.4 g). | |
3-Bromo-2-fluoro-benzoic acid 39 (15 g, 69 mmol, 1 eq) was dissolved in THF (400 mL) followed by the addition of LiAlH4 (2.9 g, 76 mmol, 1.1 eq) over the course of 5 min. The reaction mixture was stirred vigorously for 12 h, quenched with a saturated Rochelle's salt solution, and stirred for an additional 2 h. The mixture was then partitioned in DCM/saturated NaHCO3 solution and extracted with DCM (2×200 mL). The combined organics were dried over MgSO4, filtered and concentrated in vacuo to afford 11.2 g of alcohol 40. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With lithium aluminium tetrahydride; In diethyl ether; at 0 - 20℃; for 6h; | Methyl 3-bromo-2-fluorobenzoate (500 mg, 2.15 mmol) dissolved in diethyl ether (15 mL) was cooled to 0 °C and treated with lithium aluminum hydride (81 mg, 2.13 mmol). The reaction mixture was slowly warmed to room temperature and stirred for 6h. The reaction mixture was againcooled to 0 °C and methanol was added dropwise slowly followed by water. The reaction mixture wasdiluted with ethyl acetate and washed with water. The organic layer was concentrated to give (3-bromo- 2-fluorophenyl)methanol. |
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