Structure of 1214323-40-6
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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. : | 1214323-40-6 |
Formula : | C6H4ClF2NO |
M.W : | 179.55 |
SMILES Code : | FC(F)OC1=NC=C(Cl)C=C1 |
MDL No. : | MFCD13185854 |
InChI Key : | NPGYJVBYGSWAEN-UHFFFAOYSA-N |
Pubchem ID : | 66632003 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H320-H335 |
Precautionary Statements: | P264-P270-P301+P312-P330 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.17 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 35.84 |
TPSA ? Topological Polar Surface Area: Calculated from |
22.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.95 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.73 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.18 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.49 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.42 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.35 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.94 |
Solubility | 0.204 mg/ml ; 0.00114 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.85 |
Solubility | 0.254 mg/ml ; 0.00142 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.99 |
Solubility | 0.185 mg/ml ; 0.00103 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 |
-5.46 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) |
1.82 |
* 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 caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 3h; | To a solution of <strong>[4214-79-3]5-chloropyridin-2-ol</strong> (10 g, 78 mmol) in DMF (250 mL), CS2CO3 (38.0 g, 116 mmol) followed by sodium chlorodifluoroaceate (14 g, 93 mmol) was added, and the reaction mixture was heated to 100 °C for 3 h. The reaction mixture was cooled to rt; water (300 mL) was added and extracted with Et20 (500 mL x 2). The organic part was dried over sodium sulfate, filtered and concentrated to obtain a crude product, which was further purified by column chromatography using silica gel (100-200 mesh) and 0-5percent EtOAc in hexane to afford a colorless oil as 5-chloro-2-(difluoromethoxy)pyridine. 1H NMR (400 MHz, DMSO-d6) delta 8.361(d, J=2.8Hz, 1H), 8.07-8.4 (m, 1H), 7.672 (t, 1H), 7.177(d, J=8.8 Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | General procedure: Using an apparatus previously described for method B [21] , potassium hydroxide (2.52 g, 45 mmol, 15 equiv) and water (2.52 g) were added to the reaction vessel and the mixture was allowed to stir until the potassium hydroxide was almost completely dissolved. Then, 2-bromo-3-pyridinol (0.354 g, 3 mmol) was added and the mixture stirred for 30 min, after which acetonitrile (10 mL) was added via syringe and the mixture stirred at room temperature. Fluoroform was then bubbled slowly into the mixture for 2 h, after which the resulting mixture was stirred for one additional hour. After being quenched with water and extracted with ethyl acetate, the ethyl acetate layer was washed with a saturated solution on sodium hydroxide, separated and concentrated. Additional impurities were removed via column chromatography on silica gel using an 80:20 mixture of hexanes/methylene chloride to give a 53percent yield of the liquid product, 2-bromo-3-difluoromethoxypyridine (3d): |
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