Structure of 6280-96-2
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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. : | 6280-96-2 |
Formula : | C9H12O2 |
M.W : | 152.19 |
SMILES Code : | CCCOC1=C(O)C=CC=C1 |
MDL No. : | MFCD06655033 |
InChI Key : | JFSVGKRARHIICJ-UHFFFAOYSA-N |
Pubchem ID : | 80476 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H412 |
Precautionary Statements: | P273-P301+P312+P330-P302+P352-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.33 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 44.57 |
TPSA ? Topological Polar Surface Area: Calculated from |
29.46 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.29 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.21 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.18 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.8 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.0 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.1 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.38 |
Solubility | 0.632 mg/ml ; 0.00415 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.46 |
Solubility | 0.524 mg/ml ; 0.00344 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.74 |
Solubility | 0.276 mg/ml ; 0.00181 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) |
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 |
-5.66 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) |
1.24 |
* 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 |
---|---|---|
80% | Method D: The dihydroxybenzene (hydroquinone, resorcinol or catechol, 1 eq) was added to a suspension of K2CO3 (1 eq) in acetone (20 mL) and the mixture was stirred at room temperature for 2 h. The alkylating reagent (1.2 eq) was then added and the reaction mixture was heated at reflux and monitored by TLC (CHCl3). When reaction was complete, the mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was diluted with C6H6 (30 mL) and washed with aqueous NaOH (10%, 40 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford the corresponding pure dialkoxy benzene product. The basic aqueous layer was cooled in an ice bath and acidified with concentrated HCl. The solid alkoxy phenol was collected from this mixture by vacuum filtration.; 2-Butoxy phenol 2a{4} (Method C, 51%): GC (RI 1353, 98.7%); 1H NMR delta: 1.00 (t, J=7.4 Hz, 3H CH3), 1.47-1.55 (m, 2H, CH2), 1.78-1.84 (m, 2H, CH2), 4.05 (t, J=6.5 Hz, 2H, OCH2), 5.69 (broad s, 1H, OH), 6.82-6.88 (m, 3H, ArH), 6.92-6.95 (m, 1H, ArH); 13C NMR delta: 13.8, 19.2, 31.2, 68.5, 111.5, 114.4, 120.0, 121.2, 145.8; MS m/z (relative intensity): 165 (M++H, 20%), 166 (M+, 100%); IR (cm-1): 3542 (broad), 3054, 2962, 2872, 1612, 1597, 1503, 1261, 1106, 783, 741. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20.0% | With potassium hydroxide; In N,N-dimethyl-formamide; at 50.0℃; | Potassium hydroxide (160 mg, 2.8 mmol) was added to a solution of compound F (485 mg, 0.78 mmol) and 2-propokyphenol (110 mg, 0.72 mmol) in dry DMF (5 mL), and the reaction mixture was heated at 50 C overnight. After cooling to room temperature, the reaction mixture was diluted with water (20 mL) and EtOAc (20 mL), and the organic phase was separated. The aqueous phase was extracted with EtOAc (3 * 20 mL). All of the organic layers were combined, washed with brine (20 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and purified by flash chromatography on silica gel (EtOAc/hexanes = 1:1), affording target compound G1 (yield: 20.0%), mp: 103.2-104.5 C. 1H NMR (400 MHz, CDCl3) delta: 1.00 (t, J = 7.3 Hz, 3H), 1.74-1.80 (m, 2H), 3.61 (dd, J = 6.6, 9.9 Hz, 1H), 3.90-3.96 (m, 5H), 4.41-4.44 (m, 1H), 4.51-4.60 (m, 2H), 6.84-6.98 (m, 4H), 7.34-7.42 (m, 4H), 7.87 (s, 1H), 8.17 (s, 1H). The HRMS-ESI calcd for C22H24ClN3O4Na [M+Na]+ was 452.1348, with 452.1352 found experimentally. |
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