Structure of 1186637-40-0
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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. : | 1186637-40-0 |
Formula : | C6H3BrN2O |
M.W : | 199.00 |
SMILES Code : | N#CC1=C(Br)C=CC(N1)=O |
MDL No. : | MFCD20482850 |
InChI Key : | KWQPGYCCQXLCIZ-UHFFFAOYSA-N |
Pubchem ID : | 66875102 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 39.48 |
TPSA ? Topological Polar Surface Area: Calculated from |
56.65 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.19 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.54 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.01 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.41 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.15 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.06 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.86 |
Solubility | 2.76 mg/ml ; 0.0139 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.3 |
Solubility | 9.95 mg/ml ; 0.05 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.88 |
Solubility | 0.265 mg/ml ; 0.00133 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) |
No |
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 |
-7.13 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) |
1.86 |
* 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 |
---|---|---|
With silver carbonate; In toluene; at 50.0℃;Darkness; | A solution of <strong>[1186637-40-0]3-bromo-6-oxo-1,6-dihydropyridine-2-carbonitrile</strong> (from Example 15/Step 2) (1.0 eq.), silver carbonate (1.3 eq.), and benzyl bromide (1.2 eq.) in toluene (0.16 M) was stirred in the dark at 50 C. overnight. The solvent was concentrated en vacuo, and the resulting residue was purified by a COMBIFLASH system (ISCO) using 0-20% ethyl acetate in hexane to give 6-(benzyloxy)-3-bromopicolinonitrile. | |
With silver carbonate; In toluene; at 50.0℃;In the dark; | A solution of 3-bromo-6-oxo-l,6-dihydropyridme-2-carbonitrile (from Example 15 /Step 2) (1.0 eq.), silver carbonate (1.3 eq.), and benzyl bromide (1.2 eq.) in toluene (0.16 M) was stirred in the dark at 5O0C overnight. The solvent was concentrated en vacuo, and the resulting residue was purified by a COMBIFLASH system (ISCO) using 0-20% ethyl acetate in hexane to give 6-(benzyloxy)-3-bromopicolinonitrile. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With silver carbonate; In toluene; at 20.0℃;Darkness; | A solution of <strong>[1186637-40-0]3-bromo-6-oxo-1,6-dihydropyridine-2-carbonitrile</strong> (from Example 15/Step 2) (1.0 eq.), silver carbonate (1.3 eq.), and iodomethane (1.2 eq.) in toluene (0.2 M) was stirred in the dark at room temperature overnight. The solvent was concentrated en vacuo, and the resulting residue was purified by a COMBIFLASH system (ISCO) using 0-80% ethyl acetate in hexane to give 3-bromo-6-methoxypicolinonitrile. | |
With silver carbonate; In toluene; at 20.0℃;In the dark; | A solution of 3-bromo-6-oxo-l,6-dihydropyndine-2-carbonitrile (from Example 15 /Step 2) (1.0 eq.), silver carbonate (1.3 eq.), and iodomethane (1.2 eq.) in toluene (0.2 M) was stirred in the dark at room temperature overnight. The solvent was concentrated en vacuo, and the resulting residue was purified by a COMBIFLASH system (ISCO) using 0-80% ethyl acetate in hexane to give 3-bromo-6-methoxypicolinonitrile. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 1H-imidazole; In N,N-dimethyl-formamide; at 60.0℃; | A solution of 3-bromo-6-oxo-l,6-dihydropyridine-2-carbonitrile (from step 2) (1.0 eq.), tert-butyldimethylsilylchloride (TBSCl) (1.8 eq.), and imidazole (2.5 eq.) in DMF (0.2 M) was heated to 600C and stirred overnight. The reaction mixture was diluted with water and extracted with ether. The combined organic layers were dried over anhydrous MgS O4 and concentrated en vacuo The residue was purified by a COMBIFLASH system (ISCO) using 0-20% ethyl acetate in hexane to give 3-bromo-6-(^rf-butyldimethylsilyloxy)picolinonitrile. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetone; at 70.0℃; | A solution of <strong>[1186637-40-0]3-bromo-6-oxo-1,6-dihydropyridine-2-carbonitrile</strong> (from Example 15/Step 2) (1.0 eq.), potassium carbonate (1.3 eq.), and 1-iodobutane (1.2 eq.) in acetone (0.3 M) was stirred at 70 C. overnight. The solvent was concentrated en vacuo, and the resulting residue was taken up in water and ethyl acetate. The aqueous layer was extracted with ethyl acetate three times. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vacuo. The crude product was purified by a COMBIFLASH system (ISCO) using 0-30% ethyl acetate in hexane to give a colorless solid. | |
With potassium carbonate; In acetone; at 70.0℃; | A solution of 3-bromo-6-oxo-l,6-dihydropyndine-2-carbonitrile (from Example 15 /Step 2) (1.0 eq.), potassium carbonate (1.3 eq.), and 1-iodobutane (1.2 eq.) in acetone (0.3 M) was <n="178"/>stirred at 7O0C overnight. The solvent was concentrated en vacuo, and the resulting residue was taken up in water and ethyl acetate. The aqueous layer was extracted with ethyl acetate three times. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vacuo. The crude product was purified by a COMBIFLASH system (ISCO) using 0-30% ethyl acetate in hexane to give a colorless solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With water; sodium hydroxide; In methanol; at 20.0℃; for 2.0h; | A solution of 3-bromo-2-cyanopyridine 1-oxide (from step 1) in acetic anhydride (0.5M) was heated at 15O0C for 24 hours. The reaction was cooled to room temperature, and the solvent was removed en vacuo. The residue was purified by a COMBIFLASH system (ISCO) using 0-90% ethyl acetate in hexane to give the O-acetate which was hydrolyzed in 2N NaOH / methanol (1:1, 0.2 M) at room temperature for 2 hours. The resulting mixture was diluted with water and acidified with 5% citric acid. The pale yellow precipitate was filtered and washed with 9:1 hexane/ethyl acetate and ether to give 3-bromo-6-oxo-l,6-dihydropyridine-2-carbonitrile. |