Structure of 953780-40-0
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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. : | 953780-40-0 |
Formula : | C8H8FNO3 |
M.W : | 185.15 |
SMILES Code : | O=C(OC)C1=CN=C(OC)C(F)=C1 |
MDL No. : | MFCD14698157 |
InChI Key : | HJBPCUZDKHCJRR-UHFFFAOYSA-N |
Pubchem ID : | 46311253 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 41.97 |
TPSA ? Topological Polar Surface Area: Calculated from |
48.42 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.18 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.11 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.44 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.91 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.63 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.45 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.83 |
Solubility | 2.73 mg/ml ; 0.0148 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.72 |
Solubility | 3.53 mg/ml ; 0.0191 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.51 |
Solubility | 0.573 mg/ml ; 0.0031 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 |
-6.64 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) |
1.99 |
* 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 |
---|---|---|
41% | With tetrakis(triphenylphosphine) palladium(0); formic acid; triethylamine; In N,N-dimethyl-formamide; at 100℃; for 4h; | [00672] Intermediate 73c: methyl 5-fluoro-6-methoxy-pyridine-3-carboxylate[00673] Triethylamine (1 .62mL, 11.61 mmol), tetrakis(triphenylphosphine)palladium(0) (0.45g, 0.3gmmol) and formic acid (0.44mL, 11 .61 mmol) were added to a flask containing a stirring solutionof <strong>[959616-64-9]methyl 2-chloro-5-fluoro-6-methoxy-pyridine-3-carboxylate</strong> (1 .7g, 7.74mmol) in DMF (1 7mL). The reaction mixture was then heated to 100 C and left to stir for 4 hours. The reaction mixture was left to cool before being filtered through celite and the solvent removed in vacuo. The residue was taken up in EtOAc (5OmL), water (5OmL) added and the organics extracted with further EtOAc (3 x 5OmL). The organic layers were combined, dried over Na2504, filtered and concentrated in vacuo. Theresidue was purified by column chromatography using an eluent of 0-50% EtOAc in heptane) toafford the desired product methyl 5-fluoro-6-methoxy-pyridine-3-carboxylate (590mg, 3.1 9mmol,41% yield) as a white solid.1H NMR (CDCI3,400MHz) O/ppm: 8.61 (1H, d, J= 1.9Hz), 7.88 (1H, dd, J= 10.4Hz, 1.9Hz), 4.09(3H, 5), 3.92 (3H, 5),MS Method 3: RT: 5.10 mm, 186.1 m/z [M+H] |
With formic acid; triethylamine;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 20 - 100℃; for 4.33333h; | To a solution of 1.5 g of <strong>[959616-64-9]methyl 2-chloro-5-fluoro-6-methoxynicotinate</strong> in 15 mL of N,N-dimethylformamide, 0.38 g of tetrakis(triphenylphosphine)palladium(0), 1.4 mL of triethylamine, and 0.38 mL of formic acid were added at room temperature, and the mixture was stirred at 50 to 60C for 1 hour under a nitrogen atmosphere, and then stirred at 90 to 100C for 2 hours 20 minutes. Thereto were further added 1.4 mL of triethylamine, 0.38 g of tetrakis(triphenylphosphine)palladium(0) and 0.38 mL of formic acid at room temperature, and the mixture was stirred at 90 to 100C for 1 hour. After cooling to room temperature, the reaction mixture was charged with ethyl acetate and water, and adjusted to pH 4.8 with 2 mol/L hydrochloric acid. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, and the resultant solution was washed with a saturated aqueous sodium chloride solution. A mixed solvent of chloroform:methanol was added to the organic layer to dissolve the insoluble substance, and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. Ethyl acetate was added to the resultant residue, and the solid was filtered off to obtain 0.30 g of methyl 5-fluoro-6-methoxynicotinate as a yellow solid. 1H-NMR (CDCl3) delta: 3.92 (3H, s), 4.09 (3H, s), 7.88 (1H, dd, J = 10.5, 2.0 Hz), 8.61 (1H, d, J = 2.0 Hz) |
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