Structure of 697739-12-1
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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. : | 697739-12-1 |
Formula : | C10H10N2O2 |
M.W : | 190.20 |
SMILES Code : | CCOC(=O)C1=CC=CN2C=NC=C12 |
MDL No. : | MFCD20921983 |
InChI Key : | IZZCPMXJHNYFKD-UHFFFAOYSA-N |
Pubchem ID : | 69160068 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.2 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 51.28 |
TPSA ? Topological Polar Surface Area: Calculated from |
43.6 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.2 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.07 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.51 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.94 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.09 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.56 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.6 |
Solubility | 0.477 mg/ml ; 0.00251 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.61 |
Solubility | 0.462 mg/ml ; 0.00243 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.57 |
Solubility | 0.513 mg/ml ; 0.0027 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 |
-5.99 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) |
1.79 |
* 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 |
---|---|---|
[0143] A mixture of 44.8 mL of acetic anhydride and 19.2 mL of formic acid was heated in a 50-60 C oil bath temperature for 3 h and then cooled to rt to give formic-acetic anhydride, which was then slowly added to the solid ethyl 2-(aminomethyl)-3-pyridinecarboxylate HCl and then stirred at rt for 8 h. Excess reagent was evaporated to give a residue, which was neutralized by very slow addition of sat. NaHC03 solution. Solution was extracted with DCM, dried and evaporated to provide ethyl imidazo[l,5-a]pyridine-8-carboxylate as a yellow solid (crude weight 2.7 g). MS: exact mass calculated for C10H10N2O2, 190.07; m/z found, 191 [M+H] +. | ||
A mixture of 44.8 mL of acetic anhydride and 19.2 mL of formic acid was heated in a 50-60 C. oil bath temperature for 3 h and then cooled to rt to give formic-acetic anhydride, which was then slowly added to the solid ethyl 2-(aminomethyl)-3-pyridinecarboxylate HCl and then stirred at rt for 8 h. Excess reagent was evaporated to give a residue, which was neutralized by very slow addition of sat. NaHCO3 solution. _Solution was extracted with DCM, dried and evaporated to provide ethyl imidazo[1,5-a]pyridine-8-carboxylate as a yellow solid (crude weight 2.7 g). MS: exact mass calculated for C10H10N2O2, 190.07; m/z found, 191 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With potassium hydroxide; In methanol; for 0.5h;Heating / reflux; | Description 36 (8.67 g, 45.6 mmol) and KOH [1. OM in methanol] (91.2 ml, 91.2 mmol) were mixed together and heated to reflux for 30 minutes when HPLC indicated the reaction was complete. The mixture was cooled and evaporated to dryness. Water (50 ml) was then added, and the mixture acidified with 2N HC1 to give a yellow precipitate. The precipitate was filtered and washed successively with water, ethanol, and diethyl ether to give the title compound (3.1 g, 42%) as a yellow solid |
Ethyl imidazo [1, 5-a] pyridine-8-carboxylate (J. Het. CLIEIIZ., 1993,473) (0.21 g) was dissolved in 1M KOH in methanol (5 ml) and the solution heated at reflux for 5 min. The mixture was then concentrated, diluted with water (2 ml) and acidified to pH 1 with 2N HCI. The resulting precipitate was collected by filtration to give imidazo [1, 5-a] pyridine-8-carboxylic acid (80 mg) as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | Acetic anhydride (38. 21 ml, 405 mmol) and formic acid (15.28 ml, 405 mmol) were mixed together at 60 C for 2 hours then allowed to cool to room temperature. To this mixture was added Description 35 (17.55 g, 81 mmol), and the resulting mixture stirred at room temperature for 1 hour, then heated at 35 C for 3 hours. The mixture was cooled to 5 C and neutralised with 0.88 ammonia solution and then extracted with dichloromethane (3 x). The combined dichloromethane layers were washed with water, saturated NACI, dried over NA2S04, filtered and evaporated. The residue was purified by column chromatography on silica eluting with 2% MEOH in DCM + 0.5% NH40H to give the title compound (8.67 g, 56%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
[0144] To a cold solution of lithium aluminum hydride (1.62 g, 42,4 mmol, 4.0 eq) in THF (50 mL) was added the crude ethyl imidazo[l,5-a]pyridine-8-carboxylate (2.7 g, 14.2 mmol, 1.0 eq) and the reaction mixture was heated at reflux for 2 h. The reaction was cooled and water (1.7 mL), 15% NaOH (1.7 mL) and water (5.1 mL) were slowly added. Solution was diluted with excess EtOAc and stirred at rt for 30 min. The solution was filtered and the solid was washed with ethyl acetate. Organic layers were combined, dried and solvent was removed to give crude imidazo[l,5-a]pyridine-8-methanol, which was purified by column chromatography (EtOAc/ Hexane). MS: exact mass calculated for 148.06; m/z found, 149 [M+H] +. | ||
With lithium aluminium tetrahydride; In tetrahydrofuran; for 2h;Reflux; | [0251] To a cold solution of lithium aluminum hydride (1.62 g, 42,4 mmol, 4.0 eq) in THF (50 mL) was added the crude <strong>[697739-12-1]ethyl imidazo[1,5-a]pyridine-8-carboxylate</strong> (2.7 g, 14.2 mmol, 1.0 eq) and the reaction mixture was heated at reflux for 2 h. The reaction was cooled and water (1.7 mL), 15% NaOH (1.7 mL) and water (5.1 mL) were slowly added. Solution was diluted withexcess EtOAc and stirred at rt for 30 mm. The solution was filtered and the solid was washed with ethyl acetate. Organic layers were combined, dried and solvent was removed to give crude imidazo[1,5-a]pyridine-8-methanol, which was purified by column chromatography (EtOAc/ Hexane). MS: exact mass calculated for C8H8N20, 148.06; m/z found, 149 [M+H]+ . | |
With lithium aluminium tetrahydride; In tetrahydrofuran; for 2h;Reflux; | Steps 5 and 6 :To a cold solution of lithium aluminum hydride (1.62 g, 42.4 mmol, 4.0 eq) in THF (50 mL) was added the crude <strong>[697739-12-1]ethyl imidazo[1,5-a]pyridine-8-carboxylate</strong> (2.7 g, 14.2 mmol, 1.0 eq) and the reaction mixture was heated at reflux for 2 h. The reaction was cooled and water (1.7 mL), 15% NaOH (1.7 mL) and water (5.1 mL) were slowly added. Solution was diluted with excess EtOAc and stirred at rt for 30 min. The solution was filtered and the solid was washed with ethyl acetate. Organic layers were combined, dried and solvent was removed to give crude imidazo[1,5-a]pyridine-8-methanol, which was purified by column chromatography (EtOAc/Hexane). MS: exact mass calculated for C8H8N2O, 148.06; m/z found, 149 [M+H]+. |
With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃; for 2h; | To a solution of 550 <strong>[697739-12-1]ethyl imidazo[1,5-a]pyridine-8-carboxylate</strong> (2 g, 10.52 mmol) in 166 THF (20 mL) was added 192 LiAlH4 (798 mg, 21.0 mmol) with stirring at 0 C. The resulting suspension was stirred at 20 C. for 2 hours. The reaction mixture was cooled to 0 C. and was quenched with 55 water (2 mL), then diluted with ethyl acetate (200 mL). The resulting suspension was filtered through a pad of A1203 and concentrated. The residue was purified by column silica gel chromatography (Gradient: 0-10%, 113 MeOH in 68 dichloromethane) to give 551 imidazo[1,5-a]pyridin-8-ylmethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic anhydride; formyl acetic anhydride; at 20℃; for 8h; | [0250] A mixture of 44.8 mL of acetic anhydride and 19.2 mL of formic acid was heated in a 50-60 C oil bath temperature for 3 h and then cooled to rt to give formic-acetic anhydride,which was then slowly added to the solid ethyl 2-(aminomethyl)-3-pyridinecarboxylate HCl andthen stirred at rt for 8 h. Excess reagent was evaporated to give a residue, which was neutralizedby very slow addition of sat. NaHCO3 solution. Solution was extracted with DCM, dried and evaporated to provide ethyl imidazo[1,5-a]pyridine-8-carboxylate as a yellow solid (crude weight 2.7 g). MS: exact mass calculated for C10H10N202, 190.07; m/z found, 191 [M+H]+ . |
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