Structure of tert-Butyl 4-bromobenzoate
CAS No.: 59247-47-1
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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. : | 59247-47-1 |
Formula : | C11H13BrO2 |
M.W : | 257.12 |
SMILES Code : | O=C(OC(C)(C)C)C1=CC=C(Br)C=C1 |
MDL No. : | MFCD00093266 |
InChI Key : | BFJJYXUCGYOXDM-UHFFFAOYSA-N |
Pubchem ID : | 11334366 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.36 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 59.88 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.99 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.45 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.4 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.53 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.11 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.3 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.73 |
Solubility | 0.0482 mg/ml ; 0.000188 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.68 |
Solubility | 0.0533 mg/ml ; 0.000207 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.15 |
Solubility | 0.0181 mg/ml ; 0.0000703 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) |
Yes |
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 |
-5.42 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 |
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 |
0.0 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) |
1.6 |
* 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 triphenylphosphine;palladium diacetate; In triethylamine; | B. tert.-Butyl 4-Ethynylbenzoate A mixture containing 1.31 g of tert.-butyl 4-bromobenzoate, 1.0 g of trimethylsilylacetylene, 10 mg of palladium acetate and 15.6 mg of triphenylphosphine in 15 ml of anhydrous triethylamine is heated in a sealed container at 100 C. for 16 hours. After cooling to room temperature, the reaction mixture is diluted with methylene chloride and extracted with water. The organic solution is dried over anhydrous sodium sulfate and the solvent removed under reduced pressure. The dark residue is chromatographed as a column of flash silica gel using a 10% ethyl acetate-hexanes mixture as the eluent to give tert.-butyl 4-(trimethylsilylethynylbenzoate as a dark oil: NMR (CDCl3, 300 MHz) delta 0.26 (s, 9H), 1.59 (s, 9H), 7.49 (d, 2H, J=8.23 Hz), 7.91 (d, 2H, J8.23 Hz). This is dissolved in 20 ml of anhydrous methanol, and then treated with 0.1 g of anhydrous potassium carbonate. The mixture is allowed to stir at room temperature under nitrogen for 3 hours. The reaction mixture is diluted with methylene chloride, extracted with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is distilled under reduced pressure (60-70 C./0.1 mm to give 0.75 g (73% over 2 steps) of tert.-butyl 4-ethynylbenzoate as a white solid: m.p. 71.5-72 C.; NMR (CDCl3, 80 MHz) delta 1.62 (s, 9H), 3.23 (s, 1H), 7.55 (d, 2H, J=8.11 Hz), 7.96 (d, 2H, J=8.11 Hz); IR (KBr) 3240, 2970, 2100, 1700, 1600, 1450, 1365, 1300, 1250, 1160, 1115, 1015, 845 and 765 cm-1; M/S 202 M+), 187, 157, 146, 129, 101, 75 and 57. Anal. Calcd. for Cl13 H14 O2: C, 77.20; H, 6.98 Found: C, 76.86; H, 6.79. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 90℃; for 15h;Inert atmosphere; | A mixture of 2-(furan-2-yl)-4,4,5,5-tetramethyl-1,3-dioxolane (500 mg, 2.6 mmol), tert-butyl 4-bromobenzoate (512 mg, 2 mmol) and sodium carbonate (636 mg, 6 mmol), tetra(triphenylphosphine) palladium (115 mg, 0.1 mmol) in mixed solution of 1,4-dioxane (20 ml) and water (4 ml) was stirred for 15 hours at 90 C. under nitrogen atmosphere. After cooling to room temperature, the reaction mixture was concentrated to give a residue. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=10:1) to give tert-butyl 4-(furan-2-yl)benzoate (400 mg, 82%) as a yellow oil. LRMS (M+H+) m/z: calcd 244.11. found 244. 1H NMR (300 MHz, CD3OD): delta 7.99-7.96 (m, 2H), 7.78-7.75 (m, 2H), 7.63-7.62 (m, 1H), 6.94-6.93 (m, 1H), 6.57-6.56 (m, 1H), 1.61 (s, 9H). |
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