Structure of 871125-82-5
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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. : | 871125-82-5 |
Formula : | C13H12BFO3 |
M.W : | 246.04 |
SMILES Code : | FC1=CC=C(C=C1)COC2=CC=C(B(O)O)C=C2 |
MDL No. : | MFCD07784403 |
InChI Key : | HNQLLMVLGZJPJT-UHFFFAOYSA-N |
Pubchem ID : | 16218069 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 18 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.08 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 67.2 |
TPSA ? Topological Polar Surface Area: Calculated from |
49.69 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 |
2.39 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.35 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.94 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.18 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.37 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.1 |
Solubility | 0.195 mg/ml ; 0.000793 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.07 |
Solubility | 0.207 mg/ml ; 0.000842 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.24 |
Solubility | 0.0143 mg/ml ; 0.0000581 mol/l |
Class? Solubility class: Log S scale |
Moderately 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 |
-6.1 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) |
2.07 |
* 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 nickel(II) iodide; trans-2-aminocyclohexan-1-ol; sodium hexamethyldisilazane; In isopropyl alcohol; at 70℃;Inert atmosphere; | Example 40; Synthesis of N-(3,4-dimethylisoxazol-5-yl)-2-{4-[(4-fluorobenzyl)oxy]phenyl}-7-azaspiro[3.5]nonane-7-carboxamide A 0.4 M stock solution of 2-bromo-7-aza-spiro[3.5]nonane-7-carboxylic acid tert-butyl ester in anhydrous isopropanol (0.5 mL, 0.200 mmol) and a 0.024 M stock solution of trans 2-aminocyclohexanol in isopropanol (0.5 mL, 0.012 mmol, 0.06 equiv) was added to a vial containing sodium hexamethyldisilazide (0.400 mmol, 2 equiv), nickel iodide (0.012 mmol, 0.06 equiv), and <strong>[871125-82-5]{4-[(4-fluorobenzyl)oxy]phenyl}boronic acid</strong> (0.400 mmol, 2 equiv; CAS No.871125-82-5). The vial was flushed with nitrogen, capped, and shook at 70 C. overnight. The reaction mixtures were concentrated under vacuum to give the crude tert-butyl carbamate derivative. The residue was dissolved in dichloromethane (1.2 mL) and treated with 4 N HCl in dioxane (0.8 mL). After shaking for 2 h, the reaction mixture was concentrated under vacuum to give the crude amine hydrochloride salt derivative. The crude amine hydrochloride salt residue was dissolved in acetonitrile (2.0 mL) and split into two separate vials (1.0 mL, 0.1 mmol each). To the solution in one of the vials was added diisopropylethylamine (0.17 mL, 1.0 mmol, 10 equiv) followed by a solution of phenyl(3,4-dimethylisoxazol-5-yl)carbamate (0.120 mmol in acetonitrile, 1.2 equiv). After shaking overnight at rt, the reaction was concentrated under vacuum, diluted in DMSO (1.5 mL), filtered through celite, and purified by reverse phase HPLC (acetonitrile/water/0.05% trifluoroacetic acid) to give the title compound (8.5 mg). LCMS (Phenomenex Gemini C18 4.6×50 mm 5 mum (0.04% Formic Acid, 0.01% TFA/MeCN)) tR 2.23 min; m/z 464.45 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59.9% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In N,N-dimethyl-formamide; at 100 - 110℃; for 1.5h; | 10090] A mixture of (S)-ethyl 2-(5-bromo-4-(4,4-dimeth- ylpiperidin- 1 -yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy) acetate (0.049 g, 0.108 mmol), (4-((4-fluorobenzyl)oxy)phe- nyl)boronic acid (0.040 g, 0.161 mmol) and 2M Na2CO3 (0.134 ml, 0.269 mmol) in DMF (2 mE) was degassed for 10 mm. Then, Pd(Ph3P)4 (0.012 g, 10.76 tmol) was added, degassed for 5 mm and placed in a pre-heated oil bath at 100 C. After 1.5 h at 110 C., cooled and purified by prep-HPEC to afford (S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperi- din-i -yl)-5-(4-((4-fluorobenzyl)oxy)phenyl)-2,6-dimeth- ylpyridin-3-yl)acetate (0.0372 g, 0.065 mmol, 59.9% yield) as tan color solid. LCMS (M+H)=577.6. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium azide; copper(II) sulfate; In methanol; | General procedure: The compounds (3-34) were prepared by NaN3 (1.2 equiv.), CuSO4 (0.1 equiv), and boronic acids (1.2 equiv) in methanol (10 mL) were allowed to react for 1-4 h, followed by addition of water (10 mL), sodium ascorbate (0.5 equiv), and propargylated betulinic ester (1.0 equiv) ( Scheme 1 ). The contents were stirred vigorously at room temperature for 6-8 h (as monitored by TLC analysis). After completion of the reaction, the contents diluted with water and extracted with ethyl acetate three times. The combined ethyl acetate extract was washed with brine, dried over anhydrous Na2SO4 and evaporated under reduced pressure on a rota vapour. The crude product obtained thus subjected was put to column chromatography (silica gel) with appropriate EtOAc: Hexane mixture as eluent to afford the desired pure products in good yields. All the synthesized compounds were characterized by 1H NMR, 13C NMR, IR and HRMS spectroscopic analysis. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 90℃; for 12.0h;Inert atmosphere; | General procedure: A solution of 2 M K2CO3 solution (3 ml) in dioxane (3 ml) wastaken in round bottom flask and was purged with nitrogen balloonfor 5 min at room temperature. A mixture of boronic acid(1.2 mmol) and compound 15 (0.1 g, 1 mmol) was added to thisreaction mixture, and it was again purged with nitrogen for 5 min.Pd(PPh3)4 (0.05 mmol) was then added, followed by purging andallowed the reaction mixture to stir at 90 C for overnight. Aftercompletion of the reaction, product was extracted with ethyl acetate(2 50 ml). The combined organic layer was concentrated invacuo and crude reaction mixture was purified by silica gel(100e200) column chromatography using EtOAc: hexane aseluent to get desired products 9a-x. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.10113 g | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In N,N-dimethyl-formamide; at 110℃; for 8.0h; | A mixture of (S)-ethyl 2-(5 -bromo-2,6-dimethyl-4-(p-tolyl)pyridin-3 -yl)-2-(tert-butoxy)acetate (0.03 g, 0.069 mmol), (4-((4- fluorobenzyl)oxy)phenyl)boronic acid (0.034 g, 0.138 mmol) and 2MNa2CO3 (0.069 ml, 0.138 mmol) in DMF (2 mL) degassed for 10 mm. Then, Pd(Ph3P)4 (7.98 mg, 6.91.imol) was added, degassed for 5 mm and placed in a pre-heated oil bath at 110 C. After8 h, cooled and purified by prep-HPLC to afford (S)-ethyl 2-(tert-butoxy)-2-(5-(4-((4-fluorobenzyl)oxy)phenyl)-2,6-dimethyl-4-(p-tolyl)pyridin-3 -yl)acetate (0.10113 g, 0.182mmol, 264 % yield) as purple solid. ?H NMR (500MHz, CDC13) oe 7.41 - 7.36 (m, 2H),7.20 (dd, J7.7, 1.7 Hz, 1H), 7.11 -7.06 (m, 4H), 6.90-6.84 (m, 2H), 6.71 -6.63 (m,3H), 5.00 (s, 1H), 4.97 (s, 2H), 4.30 - 4.15 (m, 2H), 2.70 (s, 3H), 2.34 (s, 3H), 2.29 (s,3H), 1.30 (t, J=7.2 Hz, 3H), 0.96 (s, 9H). LCMS (M+H) = 556.4. |