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Chemical Structure| 24228-13-5 Chemical Structure| 24228-13-5

Structure of 2-Hydroxy-3-phenylpyridine
CAS No.: 24228-13-5

Chemical Structure| 24228-13-5

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Product Details of [ 24228-13-5 ]

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

Safety of [ 24228-13-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P280-P305+P351+P338-P310

Computational Chemistry of [ 24228-13-5 ] Show Less

Physicochemical Properties

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
Ertl P. et al. 2000 J. Med. Chem.

33.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.94
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

2.46
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

2.45
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

1.88
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

2.54
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.26

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-3.07
Solubility 0.146 mg/ml ; 0.000855 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.8
Solubility 0.272 mg/ml ; 0.00159 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-3.96
Solubility 0.0187 mg/ml ; 0.000109 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.6 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.85

Application In Synthesis of [ 24228-13-5 ]

* 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.

  • Downstream synthetic route of [ 24228-13-5 ]

[ 24228-13-5 ] Synthesis Path-Downstream   1~32

  • 1
  • [ 24228-13-5 ]
  • [ 106147-85-7 ]
  • 1-(5-Methyl-1-trityl-1H-imidazol-4-ylmethyl)-3-phenyl-1H-pyridin-2-one [ No CAS ]
  • 2
  • [ 24228-13-5 ]
  • [ 31557-57-0 ]
YieldReaction ConditionsOperation 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.
  • 3
  • [ 125641-55-6 ]
  • [ 24228-13-5 ]
YieldReaction ConditionsOperation 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%.
  • 6
  • [ 51166-57-5 ]
  • [ 24228-13-5 ]
  • 3-phenyl-1-(1-phenyl-2-pyrrolidin-1-yl-ethyl)-1<i>H</i>-pyridin-2-one [ No CAS ]
  • 7
  • [ 24228-13-5 ]
  • 2-[3-(<i>tert</i>-butyl-dimethyl-silanyloxy)-pyrrolidin-1-yl]-1-phenyl-ethanol [ No CAS ]
  • 1-{2-[3-(<i>tert</i>-butyl-dimethyl-silanyloxy)-pyrrolidin-1-yl]-1-phenyl-ethyl}-3-phenyl-1<i>H</i>-pyridin-2-one [ No CAS ]
  • 8
  • [ 1008-88-4 ]
  • [ 24228-13-5 ]
YieldReaction ConditionsOperation 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.
  • 9
  • [ 24228-13-5 ]
  • 1-[2-(3-hydroxy-pyrrolidin-1-yl)-1-phenyl-ethyl]-3-phenyl-1<i>H</i>-pyridin-2-one [ No CAS ]
  • 10
  • [ 24228-13-5 ]
  • [ 104813-87-8 ]
  • 11
  • [ 24228-13-5 ]
  • [ 104813-67-4 ]
  • 12
  • [ 24228-13-5 ]
  • [ 104813-61-8 ]
  • 13
  • [ 24228-13-5 ]
  • [ 104813-63-0 ]
  • 14
  • [ 24228-13-5 ]
  • [ 143075-08-5 ]
  • 16
  • [ 557-01-7 ]
  • [ 98-80-6 ]
  • [ 24228-13-5 ]
YieldReaction ConditionsOperation 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).
  • 17
  • [ 24228-13-5 ]
  • 5-fluoro-3-[2-(3-phenyl-2-oxo-2H-pyridin-1-yl)-acetylamino]-4-oxo-pentanoic acid [ No CAS ]
YieldReaction ConditionsOperation 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).
  • 18
  • tetrakis(dimethylamido)titanium(IV) [ No CAS ]
  • [ 24228-13-5 ]
  • bis(3-phenyl-2-pyridonate)bis(dimethylamido)titanium [ No CAS ]
  • 19
  • [ 13466-43-8 ]
  • [ 98-80-6 ]
  • [ 24228-13-5 ]
  • 20
  • [ 24228-13-5 ]
  • C10H30N5Ta(1+) [ No CAS ]
  • tetrakis(dimethylamido)(κ2-N,O-3-phenyl-2-pyridonato)tantalum(V) [ No CAS ]
  • 21
  • C47H42N5O3Ti [ No CAS ]
  • [ 24228-13-5 ]
  • [ 780-25-6 ]
  • [ 12125-02-9 ]
  • [ 100-46-9 ]
  • 22
  • tetrakis(dimethylamido)titanium(IV) [ No CAS ]
  • [ 24228-13-5 ]
  • tris(3-phenyl-2-pyridonate)Ti(NMe<SUB>2</SUB>) [ No CAS ]
  • 23
  • [ 142-08-5 ]
  • [ 59-88-1 ]
  • [ 24228-13-5 ]
  • 24
  • diphenyl(trifluoromethanesulfonato)-λ3-iodane [ No CAS ]
  • [ 142-08-5 ]
  • [ 24228-13-5 ]
YieldReaction ConditionsOperation 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).
  • 25
  • [ 24228-13-5 ]
  • ethyl 3-(3-bromophenyl)-3-(tritylamino)propanoate [ No CAS ]
  • ethyl 3-(3-(2-oxo-3-phenylpyridin-1(2H)-yl)phenyl)-3-(tritylamino)propanoate [ No CAS ]
YieldReaction ConditionsOperation 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).
  • 26
  • [ 24228-13-5 ]
  • ethyl 3-(3-bromophenyl)-3-(tritylamino)propanoate [ No CAS ]
  • ethyl 3-amino-3-(3-(2-oxo-3-phenylpyridin-1(2H)-yl)phenyl)propanoate [ No CAS ]
  • 27
  • [ 5470-18-8 ]
  • [ 24228-13-5 ]
  • 28
  • [ 20265-38-7 ]
  • [ 24228-13-5 ]
  • 29
  • (E)-4-((2-methoxypyridin-3-yl)diazenyl)morpholine [ No CAS ]
  • [ 24228-13-5 ]
  • 30
  • [ 53698-45-6 ]
  • [ 24228-13-5 ]
YieldReaction ConditionsOperation 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.
  • 31
  • [ 24228-13-5 ]
  • [ 51551-56-5 ]
  • 32
  • [ 24228-13-5 ]
  • (RS)-5-amino-2-phenylpentanoic acid hydrochloride [ No CAS ]
 

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Technical Information

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