Structure of 480425-35-2
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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. : | 480425-35-2 |
Formula : | C14H19BO4 |
M.W : | 262.11 |
SMILES Code : | COC(=O)C1=CC=CC(=C1)B1OC(C)(C)C(C)(C)O1 |
MDL No. : | MFCD03789258 |
InChI Key : | JBJGSVBGUBATNH-UHFFFAOYSA-N |
Pubchem ID : | 2734651 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 19 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.5 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 74.2 |
TPSA ? Topological Polar Surface Area: Calculated from |
44.76 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 |
2.76 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.77 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.54 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.77 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.57 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.24 |
Solubility | 0.151 mg/ml ; 0.000576 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.36 |
Solubility | 0.116 mg/ml ; 0.000441 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.08 |
Solubility | 0.022 mg/ml ; 0.0000839 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) |
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 |
-5.94 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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
3.01 |
* 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 |
---|---|---|
83% | With meso-tetra(p-tolyl)porphinato-palladium(II); potassium acetate; In 1,4-dioxane; at 110℃; for 7h; | General procedure: Aryl/heteroaryl bromide 1 (1 mmol), B2pin2(2), B2npg2(4) orBpin (6, 1.2 mmol), and dioxane (5 mL) are taken into a 25 mLround-bottomed flask. KOAc (2 mmol) was added and stirredthe resultant mixture at room temperature for 5 min, PdII-TpTP(0.15 mol%) was added, and the contents were refluxed on preheatedoil bath at 110 C under constant stirring in open-air.The reaction progress was ensured by TLC. After completion ofthe reaction, the mixture was cooled, dilute with water (20 mL)and extracted with tertbutylmethyl ether (3 × 10 mL). The combinedn-hexane layers were concentrated, and the crudeproduct obtained was purified by column chromatography (CC)on silica gel using a mixture of ethyl acetate and hexane (1:30)as eluent. |
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; for 2h;Reflux; Inert atmosphere; | General procedure: A mixture of substituted 3-(or 4-) bromobenzamides or 3-bromobenzoate or N-(3-(or 4-)bromophenyl)acetamide 3, (0.5 mmol), bis(pinacolato)diboron (0.14 g, 0.55 mmol), potassium acetate (0.15 g, 1.5 mmol), PdCl2(dppf) (0.03 g, 0.04 mmol) and 1,4-dioxane (10 mL) was refluxed for 2 h under nitrogen atmosphere. The solvent was evaporated under reduced pressure to afford a dark brown residue. To the residue was added intermediate 2 (0.4 mmol), sodium carbonate (0.16 g, 1.5 mmol), PdCl2(dppf) (0.03 g, 0.04 mmol), 1,2-dimethoxyethane (8 mL) and water (2 mL) and the mixture was refluxed for 2 h under nitrogen atmosphere. The mixture was evaporated under reduced pressure and purified by silica gel column chromatography using chloroform/methanol = 30: 1 as the eluent to afford the compounds T1-T6, T9-T10, T12 and T14-T21 as an off-white or a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step 1(3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanol Procedure:To a suspension of LiAlH4 (100 mg, 2.63 mmol) in THF (30 mL) was added portion-wise at room temperature methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (200 mg, 0.76 mmol). The reaction mixture was stirred at room temperature for additional 3 h. H2O (3 mL) was added dropwise at 0 C. then the mixture was filtered and concentrated under reduced pressure to give crude (3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanol (190 mg) which was used for next step without characterization or purification. | ||
With lithium aluminium tetrahydride; In tetrahydrofuran; at 20℃; for 3h; | To a suspension of LiAlH4 (100 mg, 2.63 mmol) in THF (30 mL) was added portion-wise at room temperature methyl 3-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)benzoate (200 mg, 0.76 mmol).. The reaction mixture was stirred at room temperature for additional 3 h. H20 (3 mL) was added dropwise at 0C then the mixture was filtered and concentrated under reduced pressure to give crude (3-(4,4,5,5-tetramethyl- l,3,2-dioxaborolan-2- yl)phenyl)methanol (190 mg) which was used for next step without characterization or purification. |
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