Structure of 134-52-1
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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. : | 134-52-1 |
Formula : | C12H10O2 |
M.W : | 186.21 |
SMILES Code : | OC1=CC(O)=CC=C1C2=CC=CC=C2 |
MDL No. : | MFCD00029715 |
InChI Key : | LYXCJGJSIWFKHZ-UHFFFAOYSA-N |
Pubchem ID : | 11019578 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315 |
Precautionary Statements: | P280 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 55.92 |
TPSA ? Topological Polar Surface Area: Calculated from |
40.46 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.95 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.73 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.76 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.41 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.56 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.48 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.28 |
Solubility | 0.0971 mg/ml ; 0.000522 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.23 |
Solubility | 0.109 mg/ml ; 0.000584 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.77 |
Solubility | 0.032 mg/ml ; 0.000172 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) |
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) |
Yes |
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 |
-5.5 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 |
0.0 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) |
1.51 |
* 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 |
---|---|---|
General procedure: 2-naphthylboronic acid 13 (which was prepared according to L. J. Diorazio et al., Tetrahedron, 48, 1992, 8073) (1 g, 5.8 mmol), 1,3-dimethoxy-4-bromo-2-fluorobenzene 12 (1.37 g, 5.8 mmol) obtained from Example 2, anhydrous glyme (5 mL) and tetrakis (triphenylphosphine) palladium (0) (675 mg, 0.58 mmol, Lancaster Chemical) was stirred for 15 minutes. Subsequently, potassium carbonate (1.6 g in 7 mL of water) was added and refluxed for 24 hours. The reaction mixture was poured into 1:1 10% HCl and 200 mL ethyl acetate. The organic layer was washed with water (100 mL × 2)and washed with brine (100 mL × 1). After drying over sodium sulfate, the reaction mixture was filtered, the solvent was removed to obtain 1.15 g (71%) of the dimethyl ether intermediate. This intermediate (282 mg, 1 mmol) was dissolved in anhydrous dichloromethane (5 mL), cooled to -78C under an argon atmosphere. After addition of 1M boron tribromide (5 mL, 5 mmol) in dichloromethane, this solution was stirred at -78 C. for 30 minutes. Subsequently, the mixture was stirred at 4 C for 16 hours. The reaction mixture was poured into 100 mL of ice water, and extracted with ethyl acetate (100 mL). The organic layer was washed with water (100 mL × 2) and washed with brine (100 mL × 1). After drying over sodium sulfate, the mixture was filtered, solvent was removed, and the crude product was purified by silica gel chromatography (silica gel,10% CHCl 3 in hexane mobile phase) 220 mg (86%) of solid product was obtained. This compound was prepared using essentially the same procedure as used in Example 3, in place of 2-naphthylboronic acid 13, phenyl boronic acid 17 (Aldrich Chemical) and in place of 1,3-dimethoxy-4-bromo-2-fluorobenzene 12, 1,3-dimethoxy-4-bromobenzene 15 was used. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With aluminum (III) chloride; In nitrobenzene; at 20 - 40℃; for 3h;Cooling with ice; | (b) Step 2 A solution of <strong>[134-52-1]biphenyl-2,4-diol</strong> (0.24 g, 1.3 mmol) in nitrobenzene (1.0 mL) was added with aluminum chloride (0.60 g, 4.5 mmol) at room temperature. Then, the reaction mixture was added with chloroacetyl chloride (0.60 g, 1.7 mmol) under ice cooling. The mixture was stirred at 40C for 3 hours, and then added with water, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and then the residue was subjected to silica gel column chromatography (eluted with chloroform/methanol (100:0 -> 90:10)) to obtain 6-hydroxy-5-phenylbenzofuran-3(2H)-one (0.12 g, 42%). 1H NMR (300 MHz, CDCl3) delta 4.62 (s, 2H), 6.58 (s, 1H), 7.38-7.48 (m, 3H), 7.48-7.56 (m, 2H), 7.58 (s, 1H), 12.00 (br s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 20 - 95℃; for 6h;Inert atmosphere; Sealed tube; | (a) Step 1 The synthesis was performed with reference to the known literature (). A solution of 4-bromoresorcinol (0.42 g, 2.2 mmol) in 1,2-dimethoxyethane (10 mL) was successively added with phenylboronic acid (0.37 g, 3.0 mmol), and 2 M aqueous sodium carbonate (3.5 mL), and the mixture was stirred at room temperature. After the inside of the reaction vessel was replaced with argon, the reaction mixture was added with tetrakis(triphenylphosphine)palladium(0) (0.14 g, 0.12 mmol), and the mixture was stirred at 95C for 6 hours in a sealed tube. The reaction mixture was added with ice water, the mixture was extracted with ethyl acetate, and then the organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and then the residue was subjected to silica gel column chromatography (eluted with hexane/ethyl acetate (75:25)) to obtain biphenyl-2,4-diol (0.25 g, 61%). 1H NMR (300 MHz, DMSO-d6) delta 6.30 (dd, J = 2.2 Hz, J = 8.8 Hz, 1H), 6.40 (d, J = 2.2 Hz, 1H), 7.04 (d, J = 8.8 Hz, 1H), 7.20 (m, 1H), 7.33 (m, 2H), 7.47 (d, J = 7.3 Hz, 2H), 9.31 (s, 1H), 9.34 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With methanesulfonic acid; at 130 - 135℃; for 2h; | <strong>[134-52-1]4-phenyl-1,3-dihydroxybenzene</strong> 18 (182 mg, 1 mmol) obtained from Example 5, Ketone 32 (405 mg, 1 mmol, AB part 361893) and methanesulfonic acid (10 mL) were mixed, then, the mixture was stirred at 130 to 135 C for 2 hours. The reaction mixture was cooled, and mixed with ice water (50 mL). The precipitated dye was extracted with ethyl acetate (100 mL). The organic layer was washed with water (50 mL × 2) and washed with brine (50 mL × 1). After drying over sodium sulfate, the mixture was filtered, the solvent was removed, and the crude pigment was obtained. These dyes were crystallized from chloroform to give 450 mg (81%) of pure dye. |
A108250 [85-27-8]
4-(1-Phenylethyl)benzene-1,3-diol
Similarity: 0.94