Structure of 2-Hydroxy-3-phenylpyridine
CAS No.: 24228-13-5
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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. : | 24228-13-5 |
Formula : | C11H9NO |
M.W : | 171.20 |
SMILES Code : | OC1=NC=CC=C1C2=CC=CC=C2 |
MDL No. : | MFCD04114134 |
InChI Key : | FLYJEBSUJDZJDE-UHFFFAOYSA-N |
Pubchem ID : | 2762808 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 51.7 |
TPSA ? Topological Polar Surface Area: Calculated from |
33.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.94 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.46 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.45 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.88 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.54 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.26 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.07 |
Solubility | 0.146 mg/ml ; 0.000855 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.8 |
Solubility | 0.272 mg/ml ; 0.00159 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.96 |
Solubility | 0.0187 mg/ml ; 0.000109 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 |
-5.6 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) |
1.85 |
* 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 |
---|---|---|
7.0 g (31%) | With trichlorophosphate; | A solution of <strong>[24228-13-5]3-phenyl-2-(1H)-pyridone</strong> (VIII; 20.0 g, 0.12 mole) and phosphorus oxychloride (300 mL) was refluxed for 6 hr and then slowly poured over crushed ice (300 mL). The resulting solution was made basic with ammonium hydroxide which led to formation of a precipitate. The mixture was extracted with ethyl ether (3*500 mL) and the combined organic extracts were dried (Na2 SO4). Concentration in vacuo gave a solid which was recrystallized from ethyl acetate to yield 7.0 g (31%) of 2-chloro-3-phenylpyridine (VI), m.p. 52-56. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With water; sodium acetate; bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate; In 1,2-dichloro-ethane; at 60 - 85℃; | General procedure: In a round bottom flask were added (pyridine or quinoline or isoquinoline) of nitrogen oxides (1.0eq.),PyBrOP (2.0eq.),Sodium acetate (3.0 eq.),Water (10 to 20.0 eq.),Adding 1,2-dichloroethane (substrate concentration 0.25 mol / L),And then heated to 60 ~ 85 degrees reaction,TLC followed the reaction until the end of the reaction (6 to 14 h).After completion of the reaction, petroleum ether: ethyl acetate = 5: 1 ~ 1: 1 as the mobile phase,Column chromatography gave the compounds shown in Table 1,Yield 45-92%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dihydrogen peroxide; In dichloromethane; acetic anhydride; acetic acid; | EXAMPLE 1 1-(3-Phenyl-2-pyridinyl)piperazine A mixture of 3-phenylpyridine (XI; 100.0 g, 0.64 mole) and glacial acetic acid (400 mL) was treated dropwise with 30% hydrogen peroxide (65 mL) at room temperature. The solution was gradually heated to 75 for 1.5 hr. and treated with additional hydrogen peroxide (75 mL). The reaction mixture was concentrated in vacuo and Kugelrohr distillation (145-160/0.1 Torr.) gave a quantitative yield of 110 g of an oil (X). The N-oxide oil (X) was dissolved in acetic anhydride (400 mL) and heated at reflux under nitrogen for 24 hrs. The reaction mixture was concentrated in vacuo, dissolved in methylene chloride and extracted with water (4*250 mL). The organic layer was isolated, dried (Na2 SO4), filtered, and concentrated in vacuo to a solid which was recrystallized from ethyl acetate to afford 60.3 g (45%) of 3-phenyl-2-(1H)-pyridone (VIII), m.p. 223-229. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
palladium; | 5-Fluoro-3-[2-(3-phenyl-2-oxo-2H-pyridin-1-yl)-acetylamino]-4-oxo-pentanoic acid (1A-5) was prepared from 3-phenylpyrimin-2-one. 3-Phenylpyrimin-2-one was prepared by bromination of pyrimidin-2-one (Oswald and Martinu J. Am. Chem. Soc., 1982, 104, 4142), followed by palladium mediated coupling with benzene boronic acid according to a procedure described by Damewood et al. (J. Med. Chem., 1994, 37, 3303). The rest of the synthesis was completed in a manner similar to that described in Example 2 to provide a colorless solid: IR (solid) 3392.3, 2941.1, 1745.4, 1673.9, 1635.4, 1564.0, 1396.3, 1236.2, 1203.4, 775.5, 700.9 cm-1; 1H NMR (400 MHz, DMSO) delta 2.64 (1H, m), 2.79 (1H, m), 4.21-4.81 (3H, m), 5.29 (2H,m), 6.37 (1H, m), 7.28-7.41 (3H, m), 7.62-7.25 (4H, m), 8.2-8.9 (1H, brm); 13C NMR (100 MHz, DMSO) delta 32.2, 34.8, 47.6, 51.9, 52.2, 52.3, 80.9, 82.7, 83.6, 85.4, 103.8, 104.0, 105.4, 105.5, 105.6, 127.6, 127.7, 128.2, 129.6, 137.0, 137.1, 137.2, 138.6, 138.8, 139.5, 140.1, 158.4, 160.8, 160.9, 162.7, 167.7, 168.2, 169.9, 172.1, 173.1, 202.7, 202.9; 19F (376 MHz, DMSO) delta -226.8 (t) -231.6 (t), -233.2 (t). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
5-Fluoro-3-[2-(3-phenyl-2-oxo-2H-pyridin-1-yl)-acetylamino]-4-oxo-pentanoic acid (1A-5) was prepared from 3-phenylpyrimin-2-one. 3-Phenylpyrimin-2-one was prepared by bromination of pyrimidin-2-one (Oswald and Martinu J. Am. Chem. Soc., 1982, 104, 4142), followed by palladium mediated coupling with benzene boronic acid according to a procedure described by Damewood et al. (J. Med. Chem., 1994, 37, 3303). The rest of the synthesis was completed in a manner similar to that described in Example 2 to provide a colorless solid: IR (solid) 3392.3, 2941.1, 1745.4, 1673.9, 1635.4, 1564.0, 1396.3, 1236.2, 1203.4, 775.5, 700.9 cm-1; 1H NMR (400 MHz, DMSO) delta 2.64 (1H, m), 2.79 (1H, m), 4.21-4.81 (3H, m), 5.29 (2H,m), 6.37 (1H, m), 7.28-7.41 (3H, m), 7.62-7.25 (4H, m), 8.2-8.9 (1H, brm); 13C NMR (100 MHz, DMSO) delta 32.2, 34.8, 47.6, 51.9, 52.2, 52.3, 80.9, 82.7, 83.6, 85.4, 103.8, 104.0, 105.4, 105.5, 105.6, 127.6, 127.7, 128.2, 129.6, 137.0, 137.1, 137.2, 138.6, 138.8, 139.5, 140.1, 158.4, 160.8, 160.9, 162.7, 167.7, 168.2, 169.9, 172.1, 173.1, 202.7, 202.9; 19F (376 MHz, DMSO) delta -226.8 (t) -231.6 (t), -233.2 (t). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | With tris[2-phenylpyridinato-C2,N]iridium(III); potassium acetate; In acetonitrile; at 20℃; for 6.0h;Irradiation; Inert atmosphere; Glovebox; Schlenk technique; | General procedure: The reaction of 1a with 6ais representative (Table 2, entry 9). In a glovebox filled with nitrogen, Ir(ppy)3 (3.3 mg, 0.0050 mmol),Ph2IOTf (6a, 136.4 mg, 0.25 mmol), and potassium acetate (49.1 mg, 0.50 mmol) were placed in aSchlenk tube. The tube was sealed with a septum and then taken out of the glovebox. A solution ofN-methyl-2-pyridone (1a, 136.4 mg, 1.25 mmol) in MeCN (1 mL) was added using a syringe. Themixture was stirred for 6 h under blue light LED irradiation (12 DC/3 W). Water (20 mL) was added,and extraction was done with EtOAc (15 mL x 3). The combined organic phase was dried over sodium sulfate and then concentrated in vacuo. Purification via column chromatography (Wakosil C-200,hexane/EtOAc = 20/1 to EtOAc/CH2Cl2/Et3N = 1/1/0.05) followed by GPC provided pure1-methyl-3-phenylpyridin-2(1H)-one (7aa, 25.4 mg, 0.14 mmol, 55% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
220 mg | With copper(l) iodide; potassium carbonate; In N,N-dimethyl-formamide; for 6.0h;Reflux; | To a flask containing 2-3 (750 mg, 1.45 mmol), 2-7 (373 mg, 2.19 mmol), copper(I) iodide (38 mg, 0.29 mmol), and potassium carbonate (302 mg, 2.19 mmol), N,N-dimethylformamide (2 mL) was added and the reaction was heated to reflux for 6 hours. The reaction was cooled to room temperature, diluted with saturated ammonium chloride and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with hexanes then 10% ethyl acetate in hexanes increasing to 20% to give ethyl 3-(3-(2-oxo-3-phenylpyridin-1(2H)-yl)phenyl)-3-(tritylamino)propanoate (2-8, 220 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
350 mg | With acetic acid; potassium iodide; for 6.0h;Reflux; | To a solution of 2-6 (800 mg, 4.32 mmol) in glacial acetic acid (20 mL), potassium iodide (2.15 g, 13.0 mmol) was added. The mixture was heated to reflux for 6 hours then was cooled to room temperature and concentrated. The residue was taken up in chloroform and washed with saturated aqueous sodium bicarbonate and brine. The organic layer was dried over magnesium sulfate, filtered, and concentrated under reduced pressure to give 3-phenylpyridin-2(1H)-one (2-7, 350 mg) as a yellow powder. |
A142447 [187392-96-7]
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A142447 [187392-96-7]
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