Structure of 2967-72-8
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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. : | 2967-72-8 |
Formula : | C9H9FO3 |
M.W : | 184.16 |
SMILES Code : | O=C(O)CCOC1=CC=CC=C1F |
MDL No. : | MFCD01569309 |
InChI Key : | HTFQCXHHEIUZPM-UHFFFAOYSA-N |
Pubchem ID : | 1545721 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 44.28 |
TPSA ? Topological Polar Surface Area: Calculated from |
46.53 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.64 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.64 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.1 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.79 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.85 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.8 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.09 |
Solubility | 1.49 mg/ml ; 0.00808 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.23 |
Solubility | 1.08 mg/ml ; 0.00589 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.6 |
Solubility | 0.462 mg/ml ; 0.00251 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) |
No |
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 |
-6.26 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 |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.56 |
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) |
1.56 |
* 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 |
---|---|---|
98% | 8-Fluorochroman-4-one. Oxalyl chloride (8.79 mL) and 1 drop of DMF were added to an ice cold solution of 3-(2-fluororhohenoxy)propanoic acid (9.27 g) in DCM (50 mL). The solution was stirred at 0 C for 2 hours, then aluminum chloride (7.39g, 55.42mM) was added and the solution was stirred for 16 hours at room temperature. The mixture was poured onto ice water, and extracted three times with DCM. The combined organics were washed with 0.5M NaOH and brine, then dried, evaporated, and purified by column chromatography (eluting with 20% EtOAc/Hex) to give of the title compound (8.2Og, 98%). | |
98% | 8-fluorochroman-4-one (37). Oxalyl chloride (8.79 mL) and one drop of DMF were added to an ice cold solution of 3-(2-fluorophenoxy)propanoic acid (9.27 g) in DCM (50 mL). The solution was stirred at 0 C. for two hours, aluminum chloride (7.39 g, 55.42 mM) was added and the solution was stirred for 16 hours at RT. The mixture was poured onto ice water, and extracted three times with DCM. The combined organics were washed with 0.5M NaOH and brine, dried, evaporated, and purified by column chromatography (eluding with 20% EtOAc/Hex) to give 8-fluorochroman-4-one (37) (8.20 g, 98%). 8-Fluorochroman-4-one. Oxalyl chloride (8.79 mL) and 1 drop of DMF were added to an ice cold solution of 3-(2-fluorophenoxy)propanoic acid (9.27 g) in DCM (50 mL). The solution was stirred at 0 C. for 2 hours, then aluminum chloride (7.39 g, 55.42 mM) was added and the solution was stirred for 16 hours at room temperature. The mixture was poured onto ice water, and extracted three times with DCM. The combined organics were washed with 0.5M NaOH and brine, then dried, evaporated, and purified by column chromatography (eluting with 20% EtOAc/Hex) to give of the title compound (8.20 g, 98%). | |
53% | With polyphosphoric acid; at 100℃; for 2h; | A mixture of compound (174a) (3.7 g, 20.3 mmol) in polyphosphoric acid (59.5 g, 607.6 mmol) was stirred at 100 C for 2 hours. After cooling to room temperature, the mixture was diluted with water and extracted with ethyl acetate. The organic layers were combined, washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was triturated in diethyl ether and filtered. The filtrate was concentrated to provide compound (174b) (1.80 g, 10.8 mmol, 53%) which was used without further purification. 1H NMR (300 MHz, CDCl3) delta 2.83-2.90 (m, 2H), 4.60-4.68 (m, 2H), 6.95 (td, J = 8.0/4.4 Hz, 1H), 7.30 (ddd, J = 1.4/8.0/10.6 Hz, 1H), 7.67 (td, J = 1.4/8.0 Hz, 1H). MS m/z ([M+H]+) 167. |
With polyphosphoric acid; at 100℃; for 3.5h; | Polyphosphoric acid (7.0 g) was added to the compound 1-2 (450 mg) , and the mixture was stirred at 100C for 3.5 hours. The heat source was turned off and the temperature was lowered to 75C. At that time, crushed ice was gradually added to the reaction mixture with vigorous stirring. When the temperature was returned to room temperature, the reaction solution was added to ice water. The aqueous layer was extracted with diethyl ether, and the organic layer was sequentially washed with aqueous sodium bicarbonate and brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (273 mg) .IH NMR (400 MHz, CDCl3) (ppm) : 2.89 (t, J=6.4 Hz, 2H), 4.66 (t, J=6.4 HZ, 2H), 6.98 (td, J=4.4 , 8.0 Hz, IH), 7.29-7.34 (m, IH), 7.71 (dt, J=I.5, 8.0 Hz, IH) |
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