Structure of 603-79-2
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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. : | 603-79-2 |
Formula : | C9H10O2 |
M.W : | 150.17 |
SMILES Code : | C1=CC=C(C(=C1C(O)=O)C)C |
MDL No. : | MFCD00002479 |
InChI Key : | RIZUCYSQUWMQLX-UHFFFAOYSA-N |
Pubchem ID : | 11782 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 43.33 |
TPSA ? Topological Polar Surface Area: Calculated from |
37.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.57 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.82 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.0 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.25 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.14 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.16 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.89 |
Solubility | 0.196 mg/ml ; 0.0013 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.26 |
Solubility | 0.0824 mg/ml ; 0.000549 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.53 |
Solubility | 0.446 mg/ml ; 0.00297 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) |
No |
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 |
-5.21 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 |
0.56 |
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) |
1.0 |
* 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 |
---|---|---|
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 |
---|---|---|
With thionyl chloride; In N,N-dimethyl-formamide; | (1) To 160 ml of methanol cooled to -10 C. was dropwise added 46.4 ml of thionyl chloride while stirring. To the solution was added a mixture of 24 g of 2,3-dimethyl benzoic acid and 1 ml of DMF, and the mixture was stirred at room temperature for 4 days. After concentration, the residue was dissolved in ether. The solution was washed with water, 5% sodium carbonate, and water in this order. The solvent was evaporated and the residue was purified by vacuum distillation to obtain 25.1 g of methyl 2,3-dimethylbenzoate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 2h; | 3-Aminomethyl-2-methyl-benzoic acid methyl ester: 2,3-Dimethylbenzoic acid (1.0 g, 6.66 mmol) was dissolved in DMF (15 mL) and then Cs2CO3 (1.5 equiv.) and MeI (1.2 equiv.) were added. The mixture was stirred for 2 h at room temperature then diluted with EtOAc and H2O. The organic layer was washed with H2O and a saturated LiCl solution, and then dried over MgSO4 and concentrated under reduced pressure to give sticky oil. The oil was dissolved in CCl4 (20 mL) and NBS (1.1 equiv.) and AIBN (0.1 equiv.) were added. The mixture was heated at reflux for 4 h then cooled to room temperature to give a white precipitate which was filtered off. The yellow solution was concentrated, the oil was dissolved in DMF (15 mL) and then NaN3 (1.2 equiv.) was added. The mixture was stirred for 2 h at room temperature then diluted with ethyl acetate and H2O. The organic layer was washed with H2O and a saturated lithium chloride solution, dried over MgSO4, and concentrated under reduced pressure to give sticky oil. The crude oil was dissolved in of CHCl3 (20 mL) and MeOH (20 mL), and then 10% Pd/C (0.20 g) and conc. HCl (1.5 mL) were added. The mixture was shaken under H2 gas (50 psi) for 16 h. The Pd/C was filtered through a pad of Celite and the pad was washed with a solution of 20% MeOH in CH2Cl2. The pale yellow solution was concentrated under reduced pressure, and the residual was dissolved in MeOH (10 mL) and diluted with Et2O (100 mL) to give a white precipitate. The precipitate was collected by filteration and dried to give the title compound (0.79 g, 55%). | |
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; | I-144: N2-(3,4-dimethyl-5-methoxycarbonyl)phenyl-5-methyl-N4-(2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl)-2,4-pyrimidinediamine 2,3-Dimethylbenzoic acid (1 g) and K2CO3 (1.1 g, 1.2 eq.) were suspended in DMF (10 mL). To the reaction mixture, was added iodomethane (0.5 mL, 1.2 eq.). The reaction was stirred at rt overnight, then diluted with water (80 mL). The solution was extracted with ethyl acetate (80 mL) and evaporated to give the methyl ester. 1H NMR (300 MHz, DMSO) delta 7.49 (d, J=7.8 Hz, 1H), 7.33 (d, J=7.5 Hz, 1H), 7.15 (t, J=7.8 Hz, 1H), 3.79 (s, 3H), 2.33 (s, 3H), 2.26 (s, 3H). |
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