Structure of 179117-44-3
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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. : | 179117-44-3 |
Formula : | C13H18BNO3 |
M.W : | 247.10 |
SMILES Code : | CC1(C)OB(OC1(C)C)C1=CC=C(C=C1)C(N)=O |
MDL No. : | MFCD05663887 |
InChI Key : | NWEMAGLLVQDEKL-UHFFFAOYSA-N |
Pubchem ID : | 2760588 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 18 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.46 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 71.01 |
TPSA ? Topological Polar Surface Area: Calculated from |
61.55 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 |
1.78 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.08 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.87 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.02 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.95 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.61 |
Solubility | 0.609 mg/ml ; 0.00247 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.69 |
Solubility | 0.504 mg/ml ; 0.00204 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.59 |
Solubility | 0.0632 mg/ml ; 0.000256 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) |
Yes |
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 |
-6.54 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) |
2.62 |
* 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 |
---|---|---|
75% | With (2,2,2-trifluoroethoxy)trimethylsilane; cesium fluoride; dichlorobis(trimethylphosphine)nickel In 1,4-dioxane at 100℃; for 12 h; Inert atmosphere; Sealed tube | Under an argon atmosphere,To the reaction vessel, 1.4 mg (0.005 mmol) of dichlorobis (trimethylphosphine) nickel,77.4 mg (0.5 mmol) of 4-chlorobenzamide,152 mg (1.0 mmol) of cesium fluoride,140 mg (0.55 mmol) of 4,4,5,5,4 ', 4', 5 ', 5'-octamethyl-2,2'-bi (1,3,2-dioxaborolanyl)180 mg (1.05 mmol) of trimethyl (2,2,2-trifluoroethoxy) silane and 0.5 mL of 1,4-dioxane were added and sealed,And the mixture was stirred at 100 ° C. for 12 hours.After the reaction vessel was cooled to room temperature, 1 mL of a saturated aqueous solution of ammonium chloride was added, and the mixture was extracted three times with 8 mL of ethyl acetate, and the obtained organic phases were combined.The solvent was distilled off under reduced pressure, and the residue was purified using silica gel column chromatography (hexane: chloroform: ethyl acetate = 4: 1: 0 to 4: 1: 1)92 mg (white solid, yield 75percent) of 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzamide was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate In 1,4-dioxane at 95℃; | A mixture of 2-70 (1.0 g, 5 mmol), (PinB)2 (2.28 g, 9 mmol), Pd(dppf)C12DCM (408 mg, 0.5 mmol), KOAc (980 mg, 10 mmol) and dioxane (5 mL) was degassed with N2 and stirred at 95 °C overnight. The resulting mixture was filtered and the filtrate was concentrated and purified via column chromatography on silica gel eluting with DCM/MeOH from 20/1 to 10/1 to give intermediate 2-71 (yellow solid, 975 mg, 79percent yield). LCMS (m/z):248 [M+Hj . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With ammonia; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 3 h; | Step 1 4-(4,4,5,5-Metramethyl-1,3,2-dioxaborolan-2-yl)benzamide Procedure To a mixture of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid (200 mg, 0.746 mmol), EDCI (214 mg, 1.12 mmol), HOBt (151 mg, 1.12 mmol) and Et3N (151 mg, 1.49 mmol) in DCM (20 mL) was bubbled ammonia until saturation. The mixture was stirred at room temperature for 3 h, then was filtered and the filtrate was concentrated to give residue which was purified by column chromatography (DCM:MeOH=50:1) to afford 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (90 mg, 45percent) as a yellow solid. LC-MS: 248 [M+H]+, tR=1.421 min. |
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