Structure of 478148-61-7
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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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CAS No. : | 478148-61-7 |
Formula : | C8H5NO2 |
M.W : | 147.13 |
SMILES Code : | O=CC1=CC2=C(OC=C2)C=N1 |
MDL No. : | MFCD11109706 |
InChI Key : | LKXRQBNEOKIHRW-UHFFFAOYSA-N |
Pubchem ID : | 22047533 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 39.4 |
TPSA ? Topological Polar Surface Area: Calculated from |
43.1 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.1 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.05 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.64 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.32 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.04 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.1 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.95 |
Solubility | 1.64 mg/ml ; 0.0111 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.55 |
Solubility | 4.19 mg/ml ; 0.0285 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.84 |
Solubility | 0.212 mg/ml ; 0.00144 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 |
1.0 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) |
2.01 |
* 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 |
---|---|---|
94% | With potassium dihydrogenphosphate; NaClO2; In methanol; water; dimethyl sulfoxide; | C17 (850 mg, 5.8 mmol) is dissolved in 10 mL DMSO. KH2PO4 (221 mg, 1.6 mmol) in 3 mL H2O is added and then NaClO2 (920 mg, 8.2 mmol) in 7 mL H2O is added, and the reaction is stirred 3 h at rt. The reaction is diluted with 25 mL water, the pH is adjusted to 10 with 2N NaOH, and the mixture is extracted with 3*20 mL ether. The combined ether layer is discarded. The pH of the aqueous layer is adjusted to 3.5 with 10% aqueous HCl and is extracted with 13*10 mL 10% MeOH/CH2Cl2. The MeOH/CH2Cl2 organic layer is dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to a pale oil. The residual DMSO is removed under a stream of N2 at rt to provide a white paste. The paste is dissolved in MeOH and concentrated to dryness. The white solid is washed with ether and dried to afford crude furo[2,3-c]pyridine-5-carboxylic acid (C18) (94% yield). MS (ESI) for C8H5NO3, 162.8 (M-H)-. |
94% | With potassium dihydrogenphosphate; NaClO2; In methanol; water; dimethyl sulfoxide; | C17 (850 mg, 5.8 mmol) is dissolved in 10 mL DMSO. KH2PO4 (221 mg, 1.6 mmol) in 3 mL water is added and then NaClO2 (920 mg, 8.2 mmol) in 7 mL water is added, and the reaction is stirred 3 h at rt. The reaction is diluted with 25 mL water, the pH is adjusted to 10 with 2N NaOH, and the mixture is extracted with 3*20 mL ether. The combined ether layer is discarded. The pH of the aqueous layer is adjusted to 3.5 with 10% aqueous HCl and is extracted with 13*10 mL 10% MeOH/CH2Cl2. The MeOH/CH2Cl2 organic layer is dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to a pale oil. The residual DMSO is removed under a stream of N2 at rt to provide a white paste. The paste is dissolved in MeOH and is concentrated to dryness. The white solid is washed with ether and dried to afford crude furo[2,3-c]pyridine-5-carboxylic acid (C18) (94% yield). MS (ESI) for C8H5NO3, 162.8 (M-H)-. |
94% | With sodium chlorite; potassium dihydrogenphosphate; In water; dimethyl sulfoxide; at 20℃; for 3h; | C8 (850 mg, 5.8 mmol) is dissolved in 10 mL DMSO. KH2PO4 (221 mg, 1.6 mmol) in 3 mL water is added and then NA102 (920 mg, 8.2 mmol) in 7 mL water is added, and the reaction is stirred 3h at rt. The reaction is diluted with 25 mL water, the pH is adjusted to 10 with 2N NAOH, AND the mixture is extracted with 3 x 20 mL ether. The combined ether layer is discarded. The pH of the aqueous layer is adjusted to 3.5 with 10% aqueous HC1 and is extracted with 13 X 10 mL 10% MEOH/CH2CL2. The MEOH/CH2CL2 organic layer is dried (NA2S04), filtered, and concentrated in vacuo to a pale oil. The residual DMSO is removed under a stream of N2 at rt to provide a white paste. The paste is dissolved in MEOH and is concentrated to dryness. The white solid is washed with ether and dried to afford crude furo [2,3-c] pyridine-5- carboxylic acid C9) (94% YIELD). MS (ESI) FOR CSHSNO3 162.8 (M-H)-. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With 2,2,6,6-tetramethyl-piperidine-N-oxyl; trichloroisocyanuric acid; In acetone; at 20℃; for 0.0833333h;Cooling with ice; | a-9) Preparation of furo[2,3-c]pyridine-5-carbaldehyde Furo[2,3-c]pyridin-5-yl methanol (521 mg, 3.49 mmol) was dissolved in acetone (17 mL), added 2,2,6,6-tetramethylpiperidine 1-oxyl (27 mg, 170 mumol) at room temperature. Then, the reaction solution was added 1,3,5-trichloro-2,4,6-triazinetrione (892 mg, 3.84 mmol) under ice-cold conditions, and stirred at the same temperature for 5 minutes. The reaction solution was concentrated in vacuo, added water and a saturated aqueous solution of sodium hydrogen carbonate under ice-cold conditions, extracted with ethyl acetate. The organic layer was washed with brine, 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 (488 mg (yield 95%)) was obtained as a yellow solid. 1H-NMR (CDCl3) delta: 6.98 (1H, dd, J=0.8, 2.2 Hz), 7.88 (1H, d, J=2.2 Hz), 8.32 (1H, d, J=0.8 Hz), 9.03 (1H, s), 10.18 (1H, s). |
86% | Oxalyl chloride (685AL, 7.8 mmol) is dissolved in 30 mL CH2C12 in a dry flask under N2. The flask is placed in a DRY-ICE/ACETONE bath, DMSO (1. 11 mL, 15. 6 mmol) in 5 mL CH2C12 is added drop-wise, and the mixture is stirred for 20 min. C7 (1.0 g, 6.7 mmol) in 10 mL CH2C12 is added, and the reaction is stirred 30 min at - 78C. TEA (4.7 mL, 33.5 mmol) is added, the reaction is allowed to warm to rt, is stirred 1 h, and is washed with 25 mL saturated NAHC03. The organic layer is dried (K2CO3), filtered, and concentrated in vacuo to an orange solid. The crude material is chromatographed over 50 g silica gel (230-400 mesh) eluting with 33% EtOAc/ hexane. The fractions with the desired compound are combined and concentrated to provide furo [2,3-c] PYRIDINE-5-CARBALDEHYDE (C8 AS A WHITE SOLID (86% YIELD). MS (EI) for C8HSNO2, NILZ : 147 (M) +. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | Oxalyl chloride (685 muL, 7.8 mmol) is dissolved in 30 mL CH2Cl2 in a dry flask under N2. The flask is placed in a dry-ice/acetone bath, DMSO (1.11 mL, 15.6 mmol) in 5 mL CH2Cl2 is added drop-wise, and the mixture is stirred for 20 min. C 16 (1.0 g, 6.7 mmol) in 10 mL CH2Cl2 is added, and the reaction is stirred 30 min at -78 C. TEA (4.7 mL, 33.5 mmol) is added, the reaction is allowed to warm to rt, is stirred 1 h, and washed with 25 mL saturated NaHCO3. The organic layer is dried over anhydrous K2CO3, filtered, and concentrated in vacuo to an orange solid. The crude material is chromatographed over 50 g silica gel (230-400 mesh) eluding with 33% EtOAc/hexane to provide furo[2,3-c]pyridine-5-carbaldehyde (C17) as a white solid (86% yield). MS (EI) for C8H5NO2, m/z: 147 (M)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With triethanolamine; In dichloromethane; dimethyl sulfoxide; | Oxalyl chloride (685 muL, 7.8 mmol) is dissolved in 30 mL CH2Cl2 in a dry flask under N2. The flask is placed in a dry-ice/acetone bath, DMSO (1.11 mL, 15.6 mmol) in 5 mL CH2Cl2 is added drop-wise, and the mixture is stirred for 20 min. C16 (1.0 g, 6.7 mmol) in 10 mL CH2Cl2 is added, and the reaction is stirred 30 min at -78 C. TEA (4.7 mL, 33.5 mmol) is added, the reaction is allowed to warm to rt, is stirred 1 h, and is washed with 25 mL saturated NaHCO3. The organic layer is dried over anhydrous K2CO3, filtered, and is concentrated in vacuo to an orange solid. The crude material is chromatographed over 50 g silica gel (230-400 mesh) eluding with 33% EtOAc/hexane. The fractions with the desired compound are combined and concentrated to provide furo[2,3-c]pyridine-5-carbaldehyde (C17) as a white solid (86% yield). MS (EI) for C8H5NO2, m/z: 147 (M)+. |
850 mg (86%) | With triethylamine; In dichloromethane; dimethyl sulfoxide; | Oxalyl chloride (685 muL, 7.8 mmol) is dissolved in 30 ml CH2Cl2 in a dried flask under nitrogen. The solution is cooled in a dry ice/acetone bath, is treated drop-wise with DMSO (1.11 ml, 15.6 mmol) in 1*5 ml CH2Cl2, and the mixture is stirred for 20 min. The mixture is treated with furo[2,3-c]pyridin-5-yl methanol (1.0 g, 6.7 mmol) in 1*10 ml CH2Cl2, is stirred 30 min at in a dry ice/acetone bath, and is treated with Et3N (4.7 ml, 33.5 mmol). The reaction is allowed to warm to rt, is stirred 1 h, and is washed with 1*25 ml saturated NaHCO3. The organic layer is dried over K2CO3 and is concentrated in vacuo to an orange solid. The crude material is chromatographed over 50 g silica gel (230-400 mesh) eluding with 33% EtOAc/hexane. The appropriate fractions are combined and concentrated to provide 850 mg (86%) of furo[2,3-c]pyridine-5-carbaldehyde as a white solid. MS for C8H5NO2, (EI) m/z: 147 (M)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
890 mg (94%) | In methanol; water; dimethyl sulfoxide; | Furo[2,3-c]pyridine-5-carbaldehyde (850 mg, 5.8 mmol) is dissolved in 10 ml DMSO. To this solution is added potassium dihydrogen phosphate (221 mg, 1.6 mmol) in 3 ml water followed by sodium chlorite (920 mg, 8.2 mmol) in 7 ml water. The resulting reaction mixture is stirred for 3 h at rt. The reaction is diluted with 25 ml water, the pH is adjusted to 10 with 2N NaOH, and the mixture is extracted with 3*20 ml ether. The pH of the aqueous layer is adjusted to 3.5 with 10% aqueous HCl and is extracted with 13*10 ml 10% MeOH/CH2Cl2. The organic layer is dried over Na2SO4 and is concentrated in vacuo to a pale oil. The residual DMSO is removed under a stream of nitrogen to provide a white paste. The paste is dissolved in MeOH and is concentrated to dryness. The white solid is washed with ether and is dried to give 890 mg (94%) of crude furo[2,3-c]pyridine-5-carboxylic acid. MS for C8H5NO3, (ESI): 162.8 (M-H)-. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | In tetrahydrofuran; at 20℃; for 1.5h;Cooling with ice; | a-10) Preparation of 1-(furo[2,3-c]pyridin-5-yl)ethanol Under an argon atmosphere, <strong>[478148-61-7]furo[2,3-c]pyridine-5-carbaldehyde</strong> (488 mg, 3.31 mmol) was dissolved in tetrahydrofuran (11 mL), and added methylmagnesium bromide (5.5 mL (1.0 M in THF solution), 4.97 mmol) under ice-cold conditions. Then, the mixture was stirred at room temperature for 1.5 hours. The reaction solution was added 1N-aqueous solution of hydrochloric acid under ice-cold conditions, and then a saturated aqueous solution of sodium hydrogen carbonate was added. The reaction solution was extracted with ethyl acetate. The organic layer was washed with brine, 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 (356 mg (yield 66%)) was obtained as a yellow solid. 1H-NMR (CDCl3) delta: 1.56 (3H, d, J=6.2 Hz), 5.00 (1H, q, J=6.2 Hz), 6.80 (1H, d, J=2.2 Hz), 7.53 (1H, s), 7.78 (1H, d, J=2.2 Hz), 8.80 (1H, s). |
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