Structure of 3222-50-2
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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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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 3222-50-2 |
Formula : | C7H7NO2 |
M.W : | 137.14 |
SMILES Code : | C1=NC=CC(=C1C(O)=O)C |
MDL No. : | MFCD00128869 |
InChI Key : | ZKUZSTXNVMIDCY-UHFFFAOYSA-N |
Pubchem ID : | 229163 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 36.16 |
TPSA ? Topological Polar Surface Area: Calculated from |
50.19 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.97 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.74 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.09 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.78 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.17 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.64 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.53 |
Solubility | 4.01 mg/ml ; 0.0292 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.37 |
Solubility | 5.81 mg/ml ; 0.0424 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.76 |
Solubility | 2.41 mg/ml ; 0.0175 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 |
-6.61 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) |
1.05 |
* 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 sulfuric acid; at 60℃; for 16h; | A solution of 4-methylnicotinic acid (2.00 g, 14.6 mmol) and concentrated H2SO4 (4.66 mL, 87.6 mmol) in MeOH (50 mL) was heated at about 60 C. for about 16 h. The reaction was concentrated under reduced pressure then partitioned with EtOAc (150 mL) and saturated aqueous NaHCO3 (200 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to a constant weight to afford methyl 4-methylnicotinate as a clear liquid (2.30 g, 94%): LC/MS (Table 2, Method a) Rt=1.67 min; MS m/z: 152 (M+H)+. |
81% | With sulfuric acid;Reflux; | General procedure: To a solution of carboxylic acid 22 or 29-31 (0.1mol) in dry methanol (150mL), concd H2SO4 (20mL) was added. The mixture was refluxed for 15-20h (LC-MS control). The solvent was removed in vacuo, and the residue was dissolved in H2O. The solution was made alkaline with cold saturated aq K2CO3 and extracted with CH2Cl2 (4×50mL). The combined organic extracts were dried over Na2SO4 and evaporated in vacuo. The residue was purified by flash chromatography (EtOAc as eluent) or distilled in vacuo to give 17-20. |
With oxalyl dichloride; for 16h;Reflux; | To a solution of 32.1 (1.0 eq) in MeOH (30 eq),Oxalyl chloride (2.0 eq) was added at rt. Then the mixture was stirred under refluxing condition for 16 h. After the reaction was completed, the organic solution was concentrated via rotary evaporator. The crude product 32.2 as a white solid (100% yield) was used directly in the next step without purification. ESI-MS (M+H+): 152.2. .H NMR (400 MHz, CDC13) delta: 8.92 (s, 1H), 8.60 (d, 1H), 7.39 (d, 1H), 3.87 (s, 3H), 2.54 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 3h; | In a nitrogen atmosphere, 6.89 g of potassium carbonate and 4.6 mL of methyl iodide were added in that order to N,N-dimethylformamide (100 mL) solution of 6.86 g of 4-methylnicotinic acid, and stirred at room temperature for 3 hours. The solvent was evaporated off under reduced pressure, then aqueous sodium hydrogencarbonate solution was added to the residue and extracted with chloroform. The chloroform layer was washed with saturated saline water, and dried with anhydrous sodium sulfate. The solvent was evaporated off under reduced pressure, and the residue was separated and purified through silica gel column chromatography (hexane/ethyl acetate = 50/50) to obtain 2.52 g of the entitled compound as a yellow oily substance. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58.4% | 4-Methyl-nicotinic acid 4-Methyl-nicotinic acid methyl ester (15 g, 0.1 mol) was added into the mixture of aqueous NaOH (2 M, 55 mL) and dioxane (100 mL), then the reactant was heated to 50~60 C. for 1 hour. The solvent was removed in vacuo. The residue was diluted with water (20 mL) and acidified by 1N HCl to PH?6, the solid formed was filtered and dried in vacuo to give 8.0 g of 4-methyl-nicotinic acid as a white solid in 58.4% yield. | |
58.4% | 4-Methyl-nicotinic acid4-Methyl-nicotinic acid methyl ester (15 g, 0.1 mol) was added into the mixture of aqueous NaOH (2 M, 55 mL) and dioxane (100 mL), then the reactant was heated to 50-60 C for 1 hour. The solvent was removed in vacuo. The residue was diluted with water (20 mL) and acidified by IN HC1 to PH~6, the solid formed was filtered and dried in vacuo to give 8.0 g of 4-methyl-nicotinic acid as a white solid in 58.4 % yield. | |
58.4% | With sodium hydroxide; In 1,4-dioxane; water; at 50 - 60℃; for 1h; | 4-Methyl-nicotinic acid methyl ester (15 g, 0.1 mol) was added into the mixture of aqueous NaOH (2 M, 55 mL) and dioxane (100 mL), then the reactant was heated to 50?60 C. for 1 hour. The solvent was removed in vacuo. The residue was diluted with water (20 mL) and acidified by 1N HCl to PH?6, the solid formed was filtered and dried in vacuo to give 8.0 g of 4-methyl-nicotinic acid as a white solid in 58.4 % yield. |
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