Structure of 20628-07-3
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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. : | 20628-07-3 |
Formula : | C10H12O2 |
M.W : | 164.20 |
SMILES Code : | CC(C1=CC(C)=CC=C1OC)=O |
MDL No. : | MFCD00156674 |
InChI Key : | FHIOYMGCAXTUGF-UHFFFAOYSA-N |
Pubchem ID : | 4991867 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.3 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 48.09 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.98 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.18 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.21 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.74 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.64 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.15 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.47 |
Solubility | 0.557 mg/ml ; 0.00339 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.37 |
Solubility | 0.707 mg/ml ; 0.00431 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.24 |
Solubility | 0.0947 mg/ml ; 0.000577 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 |
-5.75 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) |
1.22 |
* 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 |
---|---|---|
42% | With bromine; In diethyl ether; | This was prepared as for 25, using the crude compound 30 (18.18 g, 111 mmol) and bromine (3.77 mL,73 mmol) in diethyl ether (160 mL), with recrystallisation from the ethanol to give the product (11.22 g,42%) as grey crystals; mp 76-78 C (lit.,36 77 C); 1H NMR delta 7.62 (m, 1H, H-6), 7.31 (m, 1H, H-4), 6.89(m, 1H, H-3), 4.60 (s, 2H, CH2Br), 3.92 (s, 3H, OMe), 2.31 (s, 3H, ArMe) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With aluminum (III) chloride; In dichloromethane; at 0 - 20℃; for 3h; | l-(2-Metho l)-ethanoneI -(2-M elhoxy-5-methy]-pheny])-ethanoncLambda solution of acetyl chloride (6.79 ml, 95.1 mmol). l-Methoxy-4-methyl-benzene (intermediate LXXXVII) (9.69 g, 79.4 mmol) in 50 ml of dichloromethane was added dropwise to a suspension of aluminium chloride (12.69 g, 95.1 mmol) in 50 ml of dichloromethane at 0 C. rPhen the reaction mixture was stirred at room temperature for 3 hours. Then the reaction mixture was quenched with 1.5 N hydrochloric acid solution and extracted with dichloromethane. The combined organic extract was washed with water. brine, dried over anhydrous sodium sulphate and evaporated. The crude material was purified using column chromatography (silica gel 100-200 mesh, 15:85 ethylacetate:hexane) to afford l-(2-Methoxy-5-methyl-phenyl)-ethanone in 69 % yield. ?-Iota NMR (400 MHz, CDCI3): 7.528 (s, JH), 7.247 (bs, lH), 6.852-6.873 (d, 111, J=8.4 Hz), 3.881 (s, 3H), 2.601 (s, 3H), 2.299 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrabutylammomium bromide; sodium hydroxide; In ethanol; water; at 40 - 75℃; for 5h; | A 150-mL round bottom flask was charged with compound 6 (35.3 mmol, 5.3 g), sodium hydroxide (36.0 mmol, 1.4 g), and dimethyl sulfate (47.1 mmol, 5.2 g) in aqueous ethanol (15 mL), and tetrabutylammonium bromide (3.5 mmol, 1.1 g) was then added as catalyst. The mixture was stirred first at 40C for 30 min and then at 75C for 4.5 h and extracted with ethyl acetate, and the extract was washed with 15 ml of 5% aqueous NaOH and 50 mL of water three times in succession. The organic layer was dried with anhydrous magnesium sulfate and filtered, and the solvent was removed under reduced pressure to leave 4.55 g(78.5%) of crude compound 7. 1H NMR spectrum (CDCl3), delta, ppm: 2.31 s (3H, CH3), 2.63 s (3H, CH3), 3.89 s (3H, OCH3), 6.87 d (1H, Harom, J = 8.2 Hz), 7.27 d.d (1H, Harom, J = 2.0, 8.2 Hz), 7,54 d (1H, Harom, J = 2.0 Hz). | |
With sodium hydroxide; In water; at 90℃; for 4.5h; | The 26.48g crude product was transferred to 250mL round bottom flask,Add a small amount of tetrabutylammonium bromide or triethyl benzyl ammonium chloride,7g sodium hydroxide,15mL of water and 20mL of dimethyl sulfate,Heated to 90 reaction 4.5h,Add benzene. Obtained 5-methyl-2-methoxyacetophenone (4) crude product 28.0g,Yield 96.9% ,can be directly used for the next step reaction |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 18h; | Methyl iodide (5.02 mL, 80 mmol) was added to a stirred mixture of hydroxyacetophenone 29 (10.0 g, 67mmol) and anhydrous potassium carbonate (9.19 g, 67 mmol) in dry DMF (120 mL), and the mixture was stirred for 18 h at room temperature. The solvent was removed under vacuum, water was added, and the mixture was extracted with diethyl ether. The extracts were washed well with water to remove traces of DMF, dried and evaporated to give the product which was used without further purification; 1H NMR delta7.53 (d, J = 1.8 Hz, 1H, H-6), 7.24 (dd, J = 6.3 1.8 Hz, 1H, H-4), 6.85 (d, J = 6.3 Hz, 1H, H-3), 3.86 (s,3H, OMe), 2.60 (s, 3H, COMe), 2.28 (s, 3H, ArMe). | |
With potassium carbonate; In N,N-dimethyl-formamide; | A solution of 1 -(2-hydroxy-5-methylphenyl)ethanone (1 g, 6.66 mmol), iodomethane (0.829 mL, 13.32 mmol) and K2C03 (1 .380 g, 9.99 mmol) was stirred in N,N-Dimethylformamide (8 mL) at rt overnight. Cold water (40 mL) was added and the aqueous layer was extracted with DCM (2x50 mL). The combined organic layers were dried over Na2S04, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (petroleum ether/EtOAc = 40/1 ) to give 1 -(2-methoxy-5-methylphenyl)ethanone (1 .18 g, 7.04 mmol, 106 % yield) as a colorless oil. m/z: [M + H]+ Calcd for C10H13O2 165.2; Found 165.1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Synthesis of beta-methyl propionic acid starting from acetophenone:1.9 mmol of sodium hydride are suspended in 5 ml toluene and 1.6 mmol triethyl phosphonoacetate are added at O0C. After stirring for 30 min at O0C, 1.1 mmol of the appropriate acetophenone is dissolved in 1 ml toluene, added to the reaction mixture and the reaction mixture stirred over night or for several days at room temperature or heated to 6O0C. After addition of some water, the reaction mixture is extracted with toluene and the combined organic layers are dried over MgSO4. The crude acrylic acid ester is obtained as cis/trans mixture and used without further purification. The acrylic acid ester is suspended in a mixture of EtOH and 1 N NaOH and stirred over night at room temperature. After acidification with 1 N HCI the acrylic acid crystallizes and can be obtained by filtration. In case no crystallization can be achieved, the acrylic acid can be purified via flash chromatography. The acrylic acid is hydrogenated in MeOH with Pd/C (10%) and 1 eq. NaHCO3 under normal pressure at room temperature. After filtration over Celite, the solvent is removed and the desired beta-methyl propionic acid purified via flash chromatography if necessary. According to the above-mentioned procedure, the following compound can be prepared: Starting from 180 mg 2-methoxy-5-methyl-acetophenone, 75 mg of 2-methoxy-5-methyl crotonic acid can be obtained as cis/trans mixture. Hydrogenation of 200 mg of the crotonic acid affords 190 mg of the 3-(2-methoxy-5-methyl-phenyl)-butyric acid. Further relevant starting compounds can be prepared similarly, such as e.g. 3-(2-ethoxy-phenyl)-butyric acid from 2-ethoxy-acetophenone or, accordingly, 3-(2-methoxy-phenyl)-butyric acid or 3-(3-methoxy- phenyl)-butyric acid. |
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