Structure of Methyl 2,3-dimethylbenzoate
CAS No.: 15012-36-9
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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. : | 15012-36-9 |
Formula : | C10H12O2 |
M.W : | 164.20 |
SMILES Code : | O=C(OC)C1=CC=CC(C)=C1C |
MDL No. : | MFCD06203773 |
InChI Key : | RQTXEJYGOHZSIW-UHFFFAOYSA-N |
Pubchem ID : | 27000 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-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 | 47.65 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.34 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.11 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.09 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.55 |
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 |
2.55 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.06 |
Solubility | 0.145 mg/ml ; 0.00088 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.33 |
Solubility | 0.0767 mg/ml ; 0.000467 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 |
-5.09 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) |
1.46 |
* 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 |
---|---|---|
100% | With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; at 80℃; for 16h; | Step a. To a solution of <strong>[15012-36-9]methyl 2,3-dimethylbenzoate</strong> (CAS Number 15012-36-9, available from Accela Chembio) (5 g, 30.48 mmol) in CC14 (40 ml) were added NBS (10.8 g, 61 mmol) and AIBN (0.2 g, 0.91 mmol) at rt. The reaction mixture was heated at 80C for 16 h. The reaction mixture was filtered and evaporate to yield methyl 2,3-bis(bromomethyl)benzoate (10.1 g, quantitative). This material was used directly for the next step without further purification. |
96% | With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; for 2h;Heating / reflux; | Compound 5 (53.3 g; 0.32 mol) was dissolved in carbon tetrachloride (850 mL), under nitrogen. To the solution was added N-bromosuccinimide (115.5 g; 0.65 mol) and 2,2'-azobis(2-methyl-propionitrile (1.6 g; 0.010 mol). The reaction mixture was stirred at reflux for approximately 2 hours and the colour of this mixture changed from yellow to colorless. It was allowed to cool to room temperature and filtered off. The filtrate was evaporated in vacuo to give compound 6 (98.7 g; 96%) as a yellow liquid.1H-NMR (300 MHz, CDCI3): delta 3.95 (s, 3H), 4.68 (s, 2H), 5.14 (s, 2H), 7.36 (t, 1H), 7.55 (dd, 1 H), 7.90 (dd, 1 H). GC-MS m/z = 322. |
94% | With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 4h;Reflux; | [0506] Preparation of compound 3 (Scheme 13): To a solution of 2 (2.1 g, 13.3 mmol, 1.0 eq) in Cd4 (30 mL) was added NBS (4.7 g, 26.6 mmol, 2.0 eq) and BPO (0.2 g). The mixture was heated to reflux for 4h. The reaction was diluted with DCM (30 mL), washed by water (2 x 30 mL), dried over Na2SO4, concentrated to give a crude product, which was purified by column chromatography to give compound 3; methyl 2,3-bis(bromomethyl)benzoate (4.0 g, 94%). |
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane;Heating / reflux; | To a stirred solution of <strong>[15012-36-9]methyl 2,3-dimethylbenzoate</strong> (1.75 g, 10.7 mmol) in carbon tetrachloride (35 mL) under argon was added freshly recrystallized N-bromosuccinimide (3.90 g, 21.9 mmol) and AIBN (50 mg). The reaction mixture was heated to reflux under argon for 4 h and then cooled and filtered. Evaporation gave a yellow oil, 3.53 g, predominantly methyl 2,3-bis(bromomethyl)benzoate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With thionyl chloride;Heating / reflux; | Step 1. To a solution of 2,3-dimethylbenzoic acid (50.2 g; 0.33 mol) in MeOH (1L) was added dropwise thionyl chloride (62 mL; 0.83 mol, exothermic). The reaction mixture was stirred at reflux overnight and allowed to cool to room temperature. Evaporation of the solvent in vacuo yielded compound 5 (53.3 g; 98%) as a yellow liquid.1H-NMR (300 MHz, CDCI3): delta 2.34 (s, 3H), 3.45 (s, 3H), 3.90 (s, 3H), 7.15 (t, 1H), 7.28 (d, 1H), 7.62 (d, 1H). |
98% | With thionyl chloride; for 3h;Reflux; | [0505] Preparation of compound 2 (Scheme 13): To a solution of 1; 2,3- dimethylbenzoic acid (2.0 g, 13.3 mmol, 1.0 eq) in MeOH (30 mL) was added thionyl chloride (1.5 mL) and stirred at reflux for 3h. The mixture was concentrated, extracted with EA (30 mL). The organic layers were washed with water (2 x 30 mL),dried over Na2504, concentrated to give the desired product 2 without further purification (2.1 g, 98%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.1 g | With iron(III) chloride; thionyl chloride; In 1,2-dichloro-ethane; at 0 - 55℃; for 2h; | To a stirred solution of <strong>[15012-36-9]methyl 2,3-dimethylbenzoate</strong> (2.0 g, 12.2 mmol) in 1,2-dichloroethane (10 mL) were added chloromethyl methyl ether (5 mL, 36.0 mmol), thionylchloride (0.36 mL, 5.0 mmol) and ferric chloride (0.4 g, 2.4 mmol) at 0 C. The resulting mixture was heated to 55 C for 2 h. After cooling to room temperature, the mixture was extracted with EtOAc (3 x 100 mL) and washed with water (20 mL) and brine (20 mL). The combined organic extracts were dried over anhydrous Mg504, filtered and concentrated.Silica gel chromatography (hexane:EtOAc) afforded the title compound (1.1 g). MS (ES) m/z 213 (M+H). |
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