Structure of 473416-33-0
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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. : | 473416-33-0 |
Formula : | C8H6BFO3 |
M.W : | 179.94 |
SMILES Code : | FC1=CC=C(OC(B(O)O)=C2)C2=C1 |
MDL No. : | MFCD18383019 |
InChI Key : | YGLIPSIVUHENTJ-UHFFFAOYSA-N |
Pubchem ID : | 22260896 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 46.0 |
TPSA ? Topological Polar Surface Area: Calculated from |
53.6 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.37 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.67 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.19 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.18 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.48 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.27 |
Solubility | 0.977 mg/ml ; 0.00543 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.1 |
Solubility | 1.43 mg/ml ; 0.00797 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.46 |
Solubility | 0.63 mg/ml ; 0.0035 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 |
-6.42 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 |
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) |
2.83 |
* 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 |
---|---|---|
With n-butyllithium; In tetrahydrofuran; hexane; at -78 - 20℃; for 3.33333h; | In a nitrogen atmosphere, to a solution of 2.0 g of <strong>[24410-59-1]5-fluorobenzofuran</strong> in 150 ml tetrahydrofuran was added 18.5 ml of a 1.59 M solution of n-butyllithium in n-hexane at-78C, and the mixture was stirred at the same temperature for 10 minutes and at 0C for further 10 minutes. At -78C, 3.7 ml of triethoxyborane was added, and the mixture was stirred for 2 hours while elevating to 0C. 30 ml of 1 N hydrochloric acid was added, stirred at room temperature for 1 hour, and then the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and the solvent was evaporated. The crude product was purified and separated by silica gel column chromatography (ethyl acetate:n-hexane = 1:3 to 1:1), to give 525 mg of the title compound as colorless crystals.1H-NMR (400 MHz, CDCl3) d 7.09 (1H, dt, J = 2.4, 8.8 Hz), 7.29 (1H, dd, J = 2.4, 8.8 Hz), 7.33 (1H, s), 7.44 (1H, dd, J = 4.0, 8.8 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26% | Step 3. <strong>[24410-59-1]5-Fluorobenzofuran</strong>-2-ylboronic acid To a solution of <strong>[24410-59-1]5-fluorobenzofuran</strong> (10 g, 73.53 mmol) in dry tetrahydrofuran (250 mL) was added tetramethylethylenediamine (10.2 g, 87.93 mmol). The solution was kept below -60 C. under nitrogen, while BuLi (93.75 mmol, 2.5M solution in hexane) was added dropwise. It was warmed to -10 C. during 45 min and stirred at this temperature for another 30 min. The mixture was cooled again below -60 C. followed by dropwise addition of triisopropyl borate (41.4 g, 220.21 mmol). After warming to room temperature the mixture was quenched with hydrochloric acid (70 mL, 2N) and stirred for 1 h. The alkaline aqueous layer was brought to pH 5 and extracted with ethyl acetate (3×80 mL). All organic layers were combined, dried over sodium sulfate, and concentrated in vacuo to give <strong>[24410-59-1]5-fluorobenzofuran</strong>-2-ylboronic acid (3.5 g, 26%) which was used for the next step without further purification.1H-NMR (300 MHz, CDCl3): delta 8.63 (s, 2H), 7.58-7.62 (m, 1H), 7.44-7.49 (m, 2H), 7.15-7.22 (m, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step 3. <strong>[24410-59-1]5-Fluorobenzofuran</strong>-2-ylboronic acidTo a solution of <strong>[24410-59-1]5-fluorobenzofuran</strong> (10 g, 73.53 mmol) in dry tetrahydrofuran (250 mL) were added tetramethylethylenediamine (10.2 g, 87.93 mmol). The solution was kept below - 60C under nitrogen, while BuLi (93.75 mmlo, 2.5M solution in hexane) was added drop wise. It was warmed to -10C during 45 min and stirred at this temperature for another 30 min. The mixture was cooled again below -60C followed by dropwise addition of triisopropyl borate (41.4 g, 220.21 mmol). After warming to room temperature the mixture was quenched with hydrochloric acid (70 mL, 2N) and stirred for 1 h. The alkaline aqueous layer was brought to pH 5 and extracted with ethyl acetate (3 x 80 mL). All organic layers were combined, dried over sodium sulfate, and concentrated in vacuo to give 5- fluorobenzofuran-2-ylboronic acid (3.5 g, 26%) which was used for the next step without further purification.'H-NMR (300 MHz, CDCI3): delta 8.63 (s, 2H), 7.58 - 7.62 (m, 1H), 7.44 - 7.49 (m, 2H), 7.15 - 7.22 (m, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In methanol; toluene;Inert atmosphere; Reflux; | General procedure: <strong>[1458-01-1]Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate</strong> 2 (1 eq.) was combined with K2CO3 (10 eq.), the appropriate (het)aryl boronic acid (1.5 eq.) and Pd(PPh3)4 (5 mol%) in a two-neck round bottom flask. The flask was connected to a condenser and purged with nitrogen. A 4:1 mixture of anhydrous toluene: MeOH (60 mL) was added via syringe and the reaction mixture was heated at reflux for 0.5-18 h. The mixture was allowed to cool to room temperature and filtered through Celite (10 x 3 cm, eluting with 3 x 20 mL EtOAc). The filtrate was evaporated to dryness and the residue purified by silica gel flash column chromatography using EtOAc/pet spirit. |
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