Structure of 7588-36-5
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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. : | 7588-36-5 |
Formula : | C13H15NO3 |
M.W : | 233.26 |
SMILES Code : | O=C(OC)CC1=C(C)NC2=C1C=C(OC)C=C2 |
MDL No. : | MFCD00218549 |
InChI Key : | JYUNCKSXPPDNRM-UHFFFAOYSA-N |
Pubchem ID : | 82067 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H317 |
Precautionary Statements: | P280 |
Num. heavy atoms | 17 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.31 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 65.62 |
TPSA ? Topological Polar Surface Area: Calculated from |
51.32 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.39 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.21 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.2 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.37 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.23 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.28 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.81 |
Solubility | 0.364 mg/ml ; 0.00156 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.92 |
Solubility | 0.279 mg/ml ; 0.0012 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.29 |
Solubility | 0.012 mg/ml ; 0.0000516 mol/l |
Class? Solubility class: Log S scale |
Moderately 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 |
-6.15 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 |
0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
1.0 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) |
2.03 |
* 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% | General procedure: A reaction mixture containing the indoleacetic acid derivative (1 equivalent) and BOP-Cl (1 equivalent) in 3 mL/mmol of anhydrous CH2Cl2 is treated with triethylamine (2 equivalents) and aged at ambient temperature for 5 min. The mixture is combined with anhydrous methanol (0.14 mL/mmol) and then continuously stirred overnight at room temperature. Following dilution with dichloromethane (12 mL/mmol), the organic solution is washed with water (2x6 mL/mmol), dried over Na2SO4, and filtered. The organic filtrate is collected and concentrated in vacuo and the crude ester is purified by flash chromatography on silica gel (ethyl acetate/hexane gradient) to afford the title compound at first as viscous yellow oil, which stably crystallizes upon seeding and subsequent cold storage. | |
83% | With chloro-trimethyl-silane; at 20℃; | General procedure: Indomethacin (3.00 g, 8.39 mmol) was dissolved in 1 M NaOH(200 mL) and left to stir overnight. The reaction was acidified with1 M HCl and the precipitate filtered off. Filtrate was then extractedthree times with DCM (100 mL). Combined organic layer was driedover Na2SO4 and concentrated in vacuo to give crude 2-(5-methoxy-2-methyl-1H-indol-3-yl)acetic acid (1.12 g, 5.15 mmol). Thecrude intermediate was dissolved in MeOH (50 mL) and TMSCl(1.86 mL, 14.73 mmol) was added. The reaction mixture was leftto stir at room temperature overnight. Water (50 mL) was addedto quench the reaction and extracted three times with DCM(50 mL). Organic layer was combined, dried over Na2SO4 and concentratedin vacuo. Residue obtained was purified by column chromatographyusing CHCl3:EtOAc (10:1) to give 12 as a brown solid(0.99 g, 83%). 1H NMR (400 MHz, CDCl3) d 7.92 (s, 1H), 7.07 (d,J = 8.7 Hz, 1H), 7.01 (d, J = 2.0 Hz, 1H), 6.81-6.75 (m, 1H), 3.87 (d,J = 1.1 Hz, 3H), 3.68 (d, J = 1.0 Hz, 5H), 2.32 (s, 3H). 13C NMR(101 MHz, CDCl3) d 172.8, 154.1, 133.7, 130.2, 129.0, 111.1,110.8, 104.1, 100.4, 55.9, 51.9, 30.3, 11.7. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; In methanol; ethyl acetate; | A. 5-Methoxy-2-methyl-1H-indole-3-acetic acid methyl ester. A solution of 12.2 g (0.0557 mol) of 5-methoxy-2-methyl-1H-indole-3-acetic acid in 150 mL of MeOH and 1 mL of sulfuric acid was heated to maintain reflux for 15 hours. After cooling, the mixture was diluted with sodium bicarbonate solution and extracted with EtOAc. The EtOAc solution was washed with saturated NaCl solution and dried (Na2 SO4). The solvent was removed at reduce pressure to give 13 g of crude 5-methoxy-2-methyl-1H-indole-3-acetic acid methyl ester. | |
With sulfuric acid; In methanol; ethyl acetate; | A. 5-Methoxy-2-methyl-1H-indole-3-acetic acid methyl ester. A solution of 12.2 g (0.0557 mol) of 5-methoxy-2-methyl-1H-indole-3-acetic acid in 150 of MeOH and 1 ml of sulfuric acid was heated to maintain reflux for 15 hours. After cooling, the mixture was diluted with a sodium bicarbonate solution and extracted with EtOAc. The EtOAc solution was washed with a saturated NaCl solution and dried (Na2 SO4). The solvent was removed at reduced pressure to give 13 g of crude 5-methoxy-2-methyl-1H-indole-3-acetic acid methyl ester. | |
With sodium hydroxide; sulfuric acid; In methanol; dichloromethane; | Step 1 Methyl 5-methoxy-2-methylindole-3-acetate. To a solution of 5-methoxy-2-methylindole-3-acetic acid (10 g, 45.6 mmol) in 100 mL of methanol was added 10 drops of concentrated sulfuric acid. The reaction mixture was heated at reflux for 2 h then cooled to room temperature. The pH was adjusted to approximately or about 7 using 1N NaOH. The solvent was removed under reduced pressure. The yellow oily residue was dissolved in methylene Chloride and filtered through a plug of silica gel using 2% methanol/CH2 Cl2. The solvent was removed to give 10.6 g (quantitative) of the methyl ester as a yellow oil. |
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