Structure of 112372-15-3
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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. : | 112372-15-3 |
Formula : | C8H5NO3 |
M.W : | 163.13 |
SMILES Code : | O=C(C(O1)=CC2=C1C=NC=C2)O |
MDL No. : | MFCD11869932 |
InChI Key : | WMPIDXCJMDIDQY-UHFFFAOYSA-N |
Pubchem ID : | 13803072 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 40.97 |
TPSA ? Topological Polar Surface Area: Calculated from |
63.33 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.04 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.11 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.53 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.09 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.25 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.97 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.04 |
Solubility | 1.49 mg/ml ; 0.00913 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.03 |
Solubility | 1.51 mg/ml ; 0.00927 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.28 |
Solubility | 0.86 mg/ml ; 0.00527 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 |
-6.51 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) |
2.36 |
* 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 |
---|---|---|
89% | Stage #1: With water; potassium hydroxide In tetrahydrofuran; methanol at 20℃; for 16 h; Stage #2: With acetic acid In tetrahydrofuran; methanol |
b: furo[2,3-clpyridine-2-carboxylic acid:To a solution of ethyl furo[2,3-c]pyridine-2-carboxylate (3.82 g, 19.98 mmol) in water:THF:MeOH (1 : 1 : 1 , 60 mL) was added potassium hydroxide (3.36 g, 59.9 mmol) and the resulting mixture was stirred at ambient temperature for 16 hours. The solvent volume was then reduced to ~20 mL and acetic acid was added until pH ~4. The solids were collected by vacuum filtration, washed twice with water, and dried in a vacuum oven overnight to afford the title compound (2.90 g, 89percent). 1H NMR (DMSO-de): δ 9.09 (s, 1H), 8.47 (d, 1H), 7.81 (dd, 1H), 7.71 (d, 1H), 3.36 (br s, 1H). |
75% | With water; potassium hydroxide In tetrahydrofuran; methanol at 20℃; for 16 h; | Step 6. To a solution of ethyl furo[2,3-c]pyridine-2-carboxylate (158 g, 0.83 mol) in water:THF:MeOH (1:1:1, 2.4 L) was added KOH (139 g, 2.49 mol). Thereaction mixture was stirred at rt for 16 h and then concentrated to a volume of 750 mL. To this residue was added acetic acid until pH 4. The resulting solids were collected by filtration, washed with water (300 mLx2) and dried in a vacuum oven overnight to give the title compound (101 g, 75percent) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) 6 9.07 (s, 1H), 8,47 (d, J 5.6 Hz, 1H), 7.80 (d, J = 5.2 Hz,1H), 7.61 (s, 1H). MS (ESI+) m/z: 164 [M+F]+ |
75% | With water; potassium hydroxide In tetrahydrofuran; methanol at 20℃; for 16 h; | Step 6. To a solution of ethyl furo[2,3-cjpyridine-2-carboxylate (158 g, 0.83 mol) in water:THF:MeOH (I: 1:1, 2.4 L) was added KOH (139 g, 2.49 mol). Thereaction mixture was stirred at ii for 1 6 h and then concentrated to a volume of 750 mL. To this residue was added acetic acid until pH 4. The resulting solids were collected by filtration, washed with water (300 mLx2) and dried in a vacuum oven overnight to give the title compound (101 g, 75percent) as a pale yellow solid. 1H NMR (400 Mi-Iz, DMSO-d6) 6 9.07 (s, In), 8,47 (d, J 5.6 Hz, I H), 7.80 (d, J = 5.2 Hz,1H), 7.61 (s, IH). MS (ES1-b) ni z: 164 [M+F]+ |
75% | With water; potassium hydroxide In tetrahydrofuran; methanol at 20℃; for 16 h; | Step 6. To a solution of ethyl furo[2,3-c]pyridine-2-carboxylate ( 158 g, 0,83 mol) in water:THF:MeOH (1 : 1 : 1 , 2 4 L) was added KOH ( 139 g, 2.49 mol). The reaction mixture was stirred at rt for 1 6 h and then concentrated to a volume of 750 mL. To this residue was added acetic acid until pH ~ 4. The resulting solids were collected by filtration, washed with water (300 mL> 2) and dried in a vacuum oven overnight to give the title compound ( 101 g, 75percent) as a pale yellow solid. NMR (400 MHz, DMSO-ay δ 9.07 (s, 1 H), 8.47 (d, = 5.6 Hz, 1 H), 7.80 (d, J = 5.2 Hz, 1 H), 7.61 (s, 1 H). MS (ESI+) m. z: 1 64 [M+H] \ |
75% | With water; potassium hydroxide In tetrahydrofuran; methanol at 20℃; for 16 h; | Step 6. To a solution of ethyl furo[2,3-c]pyridine-2-carboxylate (158 g, 0.83 mol) in water:THF:MeOH (1:1:1, 2.4 L) was added KOH (139 g, 2.49 mol). Thereaction mixture was stirred at rt for 16 h and then concentrated to a volume of 750 mL. To this residue was added acetic acid until pH 4. The resulting solids were collected by filtration, washed with water (300 mLx2) and dried in a vacuum oven overnight to give the title compound (101 g, 75percent) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) 6 9.07 (s, 1H), 8,47 (d, J 5.6 Hz, 1H), 7.80 (d, J = 5.2 Hz,1H), 7.61 (s, 1H). MS (ESI+) m/z: 164 [M+F]+ |
75% | With water; potassium hydroxide In tetrahydrofuran; methanol at 20℃; for 16 h; | Intermediate 1: Furo[2,3-clpyridine-2-carboxylic acid [0171] Step 6. To a solution of ethyl furo[2,3-c]pyridine-2-carboxylate (158 g, 0.83 mol) in water:THF:MeOH (1:1:1, 2.4 L) was added KOH (139 g, 2.49 mol). The reaction mixture was stirred at rt for 16 h and then concentrated to a volume of 750 mL. To this residue was added acetic acid until pH 4. The resulting solids were collected by filtration, washed withwater (300 mLx2) and dried in a vacuum oven overnight to give the title compound (101 g, 75percent) as a pale yellow solid. ‘H NMR (400 MHz, DMSO-d6) ö 9.07 (s, 1H), 8.47 (d, J = 5.6 Hz, 1H), 7.80 (d, J = 5.2 Hz, 1H), 7.61 (s, 1H). MS (ESI+) m/z: 164 [M+Hf’. |
75% | With water; potassium hydroxide In tetrahydrofuran; methanol at 20℃; for 16 h; | Step 6. To a solution of ethyl furo[2,3-c]pyridine-2-carboxylate (158 g, 0.83 mol) in water:THF:MeOH (1 : 1 : 1, 2.4 L) was added KOH (139 g, 2.49 mol). The reaction mixture was stirred at rt for 16 h and then concentrated to a volume of 750 mL. To this residue was added acetic acid until pH ~ 4. The resulting solids were collected by filtration, washed with water (300 mLx2) and dried in a vacuum oven overnight to give the title compound (101 g, 75percent) as a pale yellow solid. 1H NMR (400 MHz, DMSO-J6) δ 9.07 (s, 1H), 8.47 (d, J = 5.6 Hz, 1H), 7.80 (d, J = 5.2 Hz, 1H), 7.61 (s, 1H). MS (ESI+) m/z: 164 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With potassium dihydrogenphosphate; NaClO2 In tetrahydrofuran; water; <i>tert</i>-butyl alcohol | C33 (558 mg, 3.79 mmol) is dissolved in 25 mL THF, 12 mL t-butanol, and 12 mL water. KH2PO4 (1.03 g, 7.6 mmol) and NaClO2 (1.28 g, 114 mmol) are added, and the reaction is stirred 3 h at rt. The reaction is concentrated in vacuo to a residue. Water (20 mL) is added, and the pH of the mixture is adjusted to 3 with 10percent aqueous HCl. The mixture is stirred 20 min in an ice bath, the resultant white solid is collected, washed with water and dried to afford furo[2,3-c]pyridine-2-carboxylic acid (C34) (84percent yield). HRMS (FAB) calculated for C8H5NO3+H: 164.0348, found 164.0344 (M+H)+. |
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