Structure of 478148-60-6
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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. : | 478148-60-6 |
Formula : | C8H7NO2 |
M.W : | 149.15 |
SMILES Code : | OCC1=CC2=C(OC=C2)C=N1 |
MDL No. : | MFCD11109707 |
InChI Key : | UUKNFBHTKFKPEH-UHFFFAOYSA-N |
Pubchem ID : | 22047174 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 40.14 |
TPSA ? Topological Polar Surface Area: Calculated from |
46.26 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.66 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.4 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.17 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.24 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.74 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.95 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.56 |
Solubility | 4.14 mg/ml ; 0.0278 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.94 |
Solubility | 17.2 mg/ml ; 0.115 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.72 |
Solubility | 0.282 mg/ml ; 0.00189 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 |
-6.93 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) |
2.25 |
* 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 |
---|---|---|
90% | With sodium hydroxide In methanol; water | C14 (770 mg, 3.48 mmol) is dissolved in 10 mL MeOH. 2N NaOH (3 mL, 6 mmol) is added, and the reaction is stirred for 1.5 h at rt. The solution is concentrated in vacuo to a residue. Water (20 mL) is added to the residue and extracted with 4*10 mL CH2Cl2. The combined organic layer is dried over K2CO3, filtered, and then concentrated in vacuo to afford furo[2,3-c]pyridin-5-yl methanol (C16) as a white solid (90percent yield). Analysis calculated for C8H7NO2: C, 64.42; H, 4.73; N, 9.39. Found: C, 64.60; H. 4.56; N, 9.44. |
90% | With sodium hydroxide In methanol; water at 20℃; for 1.5 h; | C6 (770 mg, 3.48 mmol) is dissolved in 10 mL MEOH. 2N NAOH (3 mL, 6 mmol) is added, and the reaction is stirred for 1.5 h at rt. The solution is concentrated in vacuo to a residue. Water (20 mL) is added to the residue and extracted with 4 x 10 mL CH2C12. The combined organic layer is dried (K2CO3), filtered, and then concentrated in vacuo to afford furo [2,3-c] PYRIDIN-5-YL methanol (2 AS A WHITE SOLID (90percent yield). Analysis calculated for CSH7NO2 : C, 64.42 ; H, 4.73 ; N, 9.39. Found: C, 64.60 ; H, 4.56 ; N, 9.44. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With hydrogenchloride; zinc In ethanol; water at 70℃; for 1 h; Heating / reflux | C4 (32.0 g, 174 mmol) is combined with zinc powder (34.2 g, 523 mmol) in absolute EtOH (900 mL), using an overhead stirrer. The mixture is heated to 70°C, HC1 (87.2 mL, 1.05 mol) is added slowly drop-wise, and the mixture is heated to reflux for 1 h. The mixture is cooled slightly, filtered to remove the metallic zinc and concentrated to near-dryness. The yellow oil is diluted with H20 (150 mL) and EtOAc (950 mL) and is treated slowly drop-wise with 20percent Na2C03 (310 mL) as the mixture is warmed to reflux. The vigorously stirred (using overhead stirrer) mixture is refluxed for 1 h, cooled slightly and the organics removed via cannula under reduced pressure. Additional EtOAc (600 mL) is added, the mixture is heated to reflux for 1 h, cooled slightly and the organics removed as above. More EtOAc (600 mL) is added, the mixture is stirred at rt overnight then heated to reflux for 1 h, cooled slightly and most of the organics removed as above. The remaining mixture is filtered through celite, rinsed with EtOAc until no additional product elutes, and the layers separated. The aqueous layer is further extracted with EtOAc (2 X 400 mL). The combined organics are dried (MGS04) and concentrated to a dark yellow solid (23.6 g). The crude material is chromatographed over 900 g slurry-packed silica gel, eluting with 60percent EtOAc/hexane (3 L), 70percent EtOAc/hexane (2 L), and finally 100percent EtOAc. The appropriate fractions are combined and concentrated in vacuo to'afford C7 (19.5 g, 75percent) as a white solid. Anal. Calcd for CgH7NO2 : C, 64.42 ; H, 4.73 ; N, 9. 39 ; Found: C, 64.60 ; H, 4.56 ; N, 9.44. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | at 20℃; | a-8) Preparation of furo[2,3-c]pyridin-5-yl methanol Furo[2,3-c]pyridin-5-yl methyl acetate (722 mg, 3.78 mmol) was dissolved in methanol (19 mL), added potassium carbonate (1.04 g, 7.56 mmol) at room temperature, and the mixture was stirred at room temperature overnight. The reaction solution was added 1N-aqueous solution of hydrochloric acid under ice-cold conditions, and extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, and concentrated in vacuo. The obtained residue was purified by silica-gel column chromatography (hexane/ethyl acetate), and the title compound (521 mg (yield 92percent)) was obtained as a yellow oil. 1H-NMR (CDCl3) δ: 3.68 (1H, s), 4.85 (2H, s), 6.79 (1H, s), 7.54 (1H, s), 7.79 (1H, s), 8.83 (1H, s). |
70% | With sodium hydroxide In 1,4-dioxane; water | (d) Furo[2,3-c]pyridin-5-ylmethanol A solution of furo[2,3-c]pyridin-5-ylmethyl acetate (1.15 g) in 1,4-dioxane (30 ml) and water (10 ml) was treated with 2M sodium hydroxide (12 ml) then stirred at ambient temperature for 18hrs. The mixture was then partitioned between ethyl acetate and water. The organics were separated and dried then evaporated to dryness. This gave an oil (0.63 g, 70percent). MS (+ve ion electrospray) m/z 150 (MH+). |
70% | With sodium hydroxide; water In 1,4-dioxane at 20℃; for 18 h; | (d) Furo[2,3-c]pyridin-5-ylmethanol A solution of furo[2,3-c]pyridin-5-ylmethyl acetate (1.15 g) in 1,4-dioxane (30 ml) and water (10 ml) was treated with 2M sodium hydroxide (12 ml) then stirred at ambient temperature for 18 hrs. The mixture was then partitioned between ethyl acetate and water. The organics were separated and dried then evaporated to dryness. This gave an oil (0.63 g, 70percent). MS (+ve ion electrospray) m/z 150 (MH+). |
70% | With sodium hydroxide; water In 1,4-dioxane at 20℃; for 18 h; | (d) Furo[2,3-c]pyridin-5-ylmethanol; A solution of furo[2,3-clpyridin-5-ylmethyl acetate (1.15 g) in 1 ,4-dioxane(30 ml) and water (10 ml) was treated with 2M sodium hydroxide (12 ml) then stirred at ambient temperature for 18h. The mixture was then partitioned between <n="35"/>ethyl acetate and water. The organic fractions were separated and dried then evaporated to dryness. This gave an oil (0.63 g, 70percent).MS (+ve ion electrospray) m/z 150 (MH+). |
70% | With sodium hydroxide; water In 1,4-dioxane at 20℃; for 18 h; | (d) Furo[2,3-c]pyridin-5-ylmethanol; A solution of furo[2,3-c]pyridin-5-ylmethyl acetate (1.15 g) in 1,4-dioxane (30ml) and water (10ml) was treated with 2M sodium hydroxide (12ml) then stirred at ambient temperature for 18h. The mixture was then partitioned between ethyl acetate and water. The organic fractions were separated and dried then evaporated to dryness. This gave an oil (0.63g, 70percent). MS (+ve ion electrospray) m/z 150 (MH+). |
70% | With sodium hydroxide; water In 1,4-dioxane at 20℃; for 18 h; | (d) Furo [2,3 -c]pyridin-5 -ylmethanol; A solution of furo[2,3-c]pyridin-5-ylmethyl acetate (1.15 g) in 1,4-dioxane (30 ml) and water (10 ml) was treated with 2M sodium hydroxide (12 ml) then stirred at ambient temperature for 18hrs. The mixture was then partitioned between ethyl acetate and water. The organics were separated and dried then evaporated to dryness. This gave an oil (0.63 g, 70percent). MS (+ve ion electrospray) m/z 150 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | for 18 h; Heating / reflux | (c) Furo[2,3-clpyridin-5-ylmethyl acetate; {5-Hydroxy-4-[(trimethylsilyl)ethynyl]-2-pyridinyl}methyl acetate, trifluoroacetate) (10 g, 22 mmol) was dissolved in pyridine (200 ml) and treated with copper(l) iodide (5.2 g, 27 mmol) then heated under reflux for 18hrs. The mixture was allowed to cool, evaporated to dryness and the residue partitioned between ethyl acetate and water. This mixture was filtered through kieselguhr to remove copper residues. The organic layer was separated from the filtrate, dried and chromatographed on silica gel, eluting with a gradient of 10 - 60percent ethyl acetate in 40-600C petroleum ether. This gave furo[2,3-c]pyridin-5-ylmethyl acetate (1.15 g, 27percent) and a less polar product [2-(trimethylsilyl)furo[2,3-clpyridin- 5-yl]methyl acetate (1.3 g, 23percent) as oils.MS (+ve ion electrospray) m/z 192 (MH+) and MS (+ve ion electrospray) m/z 264 (MH+). |
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