Structure of 83570-42-7
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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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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 83570-42-7 |
Formula : | C10H8N2O |
M.W : | 172.18 |
SMILES Code : | CC(C1=CC=C2N=CC=NC2=C1)=O |
MDL No. : | MFCD09880611 |
InChI Key : | DZJNWCSVQXNMFO-UHFFFAOYSA-N |
Pubchem ID : | 22631249 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.1 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 49.73 |
TPSA ? Topological Polar Surface Area: Calculated from |
42.85 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 |
1.27 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.83 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.53 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.25 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.49 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.21 |
Solubility | 1.06 mg/ml ; 0.00615 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.77 |
Solubility | 2.93 mg/ml ; 0.017 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.66 |
Solubility | 0.0378 mg/ml ; 0.000219 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 |
-6.45 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) |
1.38 |
* 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 |
---|---|---|
75.7% | at 0 - 20℃; for 2 h; Inert atmosphere | To a solution of Compound 2 (1 g, 4.6 mmol) in dry THF (10 mL) at 0 °C under N2 was added MeMgBr (2 mL, 3.0 mol/L, 6 mmol) dropwise. The resulting solution was slowly warm to RT over 2 hours. The mixture was diluted with NH4C1 solution and extracted with EA. The organic extracts were concentrated to give a crude oil. The crude product was purified by silica gel chromatography to afford Compound 3 (600 mg, 75.7 percent). |
74% | at 0 - 20℃; for 3 h; | A mixture of quinoxaline-6-carboxylic acid (2 g, 11.49 mmol) and thionyl chloride (30 mL) was stirred at reflux for 2 hours. The reaction mixture was concentrated to dryness using a rotary evaporator to afford quinoxaline-6- EPO <DP n="101"/>carboxylic acid chloride (crude quantitative). A solution of the above acid chloride (11.49 mmol) in DCM (50 mL) and pyridine (20 mL) was mixed with N,O-dimethyl hydroxylamine HCI salt (2.24 g, 23 mmol) and stirred at room temperature for 12 hours. The reaction was quenched by adding aqueous HCI (50 mL, 1 N), extracted with DCM (3x100 mL), concentrated using a rotary evaporator. The residue was further purified by column (Siψ2, Hexanes/EtOAc = 1 :3) to yield quinoxaline-6-carboxylic acid methoxy-methyl-amide (2 g, 80percent). To a solution of the above Weinreb amide (2.0 g, 9.2 mmol) in THF (30 mL) at O0C was added methyl magnesium bromide (3.9 mL, 11.6 mmol). The reaction mixture was stirred at O0C for 2 hours and then 1 hour at room temperature, quenched by adding aqueous HCI (20 mL, 1 N), extracted with DCM (3x100 mL), concentrated using a rotary evaporator. The residue was further-purified by column (SiO2, Hexanes/EtOAc = 1 :3) to yield 6-acetylquinoxaline (1.17 g, 74percent). A solution of 2- chloronicotinic acid ethyl ester (5.0 g, 27 mmol) in MeOH (25 mL) was mixed with sodium methoxide (25.6 mL, 112.5 mmol) and stirred at reflux for 12 hours. The reaction was quenched by adding water (100 mL), extracted with DCM (3x100 mL), concentrated using a rotary evaporator to afford 2-methoxynicotinic acid methyl ester (3.2 g, 71percent). A solution of 6-acetylquinoxaline (0.62 g, 3.6 mmol), 2- methoxynicotinic acid methyl ester (0.64 g, 3.8 mmol), and sodium hydride (0.46 g, 11.4 mmol) in THF (100 mL) was stirred at room temperature for 16 hours. The reaction was quenched by adding water (100 mL) and AcOH (20 mL), extracted with dichloromethane (3x100 mL), and concentrated using a rotary evaporator. The residue was re-dissolved in DCM (5 mL) and MeOH (3 mL) and was diluted with Hexanes (50 mL). The solid was removed by filtration and the filtrate was concentrated to afford the diketo compound (0.7 g, 60percent). A solution of the above diketone (0.4 g, 1.3 mmol) in AcOH (50 mL) and sulfuric acid (cone, 15 drops) was stirred at reflux for 1 hour. Most of the solvent was removed using a rotary evaporator. The residue was re-dissolved in MeOH and neutralized with potassium carbonate to pH = 8. The solid residue was removed by filtration, washed with MeOH and DCM. The filtrate was extracted with CH2CI2 (3x100 mL) and concentrated using a rotary evaporator. The solid residue was purified by column (SiO2, Hexanes/EtOAc/MeOH = 2:2:1) to afford 2-(quinoxalin-6-yl)-4H- EPO <DP n="102"/>pyrano[2,3-b]pyridin-4-one (90 mg, 24percent); MS (ES) m/z: 276 (M+1 ); MP 272.3- 274.80C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With bis-triphenylphosphine-palladium(II) chloride In toluene at 20 - 90℃; | To a degassed stirred solution of 6-bromo quinoxaline (2.0 g, 9.50 mmol) in toluene (20 mL), 1- ethoxy vinyl tributyltin (3.8 g, 10.5 mmol) followed by Pd(PPh3)2CI2 (0.67 g, 0.95 mmol) were added at RT and stirred at 90 °C overnight. After completion of the reaction (monitored by TLC), the reaction mixture was cooled to RT, filtered through celite and the obtained filtrate was evaporated under vacuum. To the resulting crude mixture, 6 N HCI solution (20 mL) was added and the mixture was stirred at RT for 1 h. The solution was neutralized with sat. NaHC03 and the aqueous layer was extracted with DCM (2 x 100 mL). The combined organic layer was dried over Na2S04 and concentrated under vacuum. The resulting crude material was purified by flash chromatography (Biotage Isolera, eluent: 30percent EtOAc in hexane) to afford the title compound. Yield: 45percent (800 mg, brown solid). 1H NMR (400 MHz, DMSO-tf6): δ 9.06-9.04 (m, 2H), 8.70 (d, J = 2.4 Hz, 1 H), 8.28 (dd, J = 8.8, 2.8 Hz, 1 H), 8.16 (d, J = 8.4 Hz, 1 H), 2.97 (s, 3H). LCMS: (Method A) 173 (M+H), Rt. 2.2 min, 99.1 percent (Max). |
A169952 [1233318-23-4]
Methyl 2-(quinoxalin-6-yl)acetate
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