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Structure of 19346-46-4

Chemical Structure| 19346-46-4

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Product Details of [ 19346-46-4 ]

CAS No. :19346-46-4
Formula : C6H5FN2O2
M.W : 156.11
SMILES Code : O=[N+](C1=CN=C(F)C(C)=C1)[O-]
MDL No. :MFCD03095069
InChI Key :CFKHKTLGKNBEPI-UHFFFAOYSA-N
Pubchem ID :12408184

Safety of [ 19346-46-4 ]

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

Computational Chemistry of [ 19346-46-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.17
Num. rotatable bonds 1
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 37.98
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

58.71 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.2
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

1.48
Log Po/w (WLOGP)?

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

1.86
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.

0.86
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

0.09
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.1

Water Solubility

Log S (ESOL):?

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

-2.08
Solubility 1.3 mg/ml ; 0.00836 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.

-2.32
Solubility 0.747 mg/ml ; 0.00479 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

-2.06
Solubility 1.37 mg/ml ; 0.00875 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

No
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.

-6.2 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

3.0 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)

2.05

Application In Synthesis of [ 19346-46-4 ]

* 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 [ 19346-46-4 ]

[ 19346-46-4 ] Synthesis Path-Downstream   1~11

  • 2
  • [ 19346-46-4 ]
  • [ 1006302-32-4 ]
YieldReaction ConditionsOperation in experiment
15% With N-Bromosuccinimide; In dichloromethane; at 20℃; for 48h; 3-Bromomethyl-2-fluoro-5-nitro-pyridine:; 2-Fluoro-3-methyl-5-nitro-pyridine (445 mg, 2.85 mmol) was dissolved in 20 mL DCM. NBS (1.01 g, 5.7 mmol, 2 eq.) was added. The reaction was stirred at room temperature for 2 days. HPLC showed 20% conversion. The reaction was concentrated down and purified (silica gel, 0-80% EtOAc/hexane) to give light yellow oil (100 mg, 15%). 1H NMR (300 MHz, CD3OD): delta 8.39 (m, 2H), 7.61 (m, 1H), 4.86 (s, 2H).
  • 3
  • [ 22280-56-4 ]
  • [ 2751-90-8 ]
  • [ 19346-46-4 ]
YieldReaction ConditionsOperation in experiment
60% With KF; In hexane; acetonitrile; 18a. 2-fluoro-3-methyl-5-nitropyridine 2-Chloro-3-methyl-5-nitropyridine (15 g, 86.9 mmol; from Maybridge Chemical Co.), KF (12 g, 258 mmol) and tetraphenylphosphonium bromide (20 g, 47.7 mmol; Aldrich) were combined in 200 mL of acetonitrile and heated at reflux for 4 days. The mixture was diluted with Et2 O (500 mL) and filtered, and the filtrate was concentrated. The residue was triturated with hot hexane (4*200 mL), and the hexane solutions were combined and concentrated to afford the title compound as a solid (8.4 g, 60%): 1 H NMR (DMSO-d6, 300 MHz) delta2.42 (s, 3H), 8.43 (m, 1H), 8.95 (dd, J=1.6 Hz, 1H); MS (CI/NH3) m/z: 157 (M+H)+.
  • 4
  • [ 19346-46-4 ]
  • [ 186593-48-6 ]
YieldReaction ConditionsOperation in experiment
78% palladium-carbon; In ethanol; 18b. 5-amino-2-fluoro-3-methylpyridine <strong>[19346-46-4]2-Fluoro-3-methyl-5-nitropyridine</strong> (8.2 g, mmol) was combined with 5% Pd/C (100 mg) in EtOH (100 mL) under a H2 atmosphere for 16 hours. The mixture was filtered and concentrated, and the crude product was chromatographed (silica gel; CHCl3 /MeOH 99:1 to 96:4) to afford a solid (5.2 g, 78%): 1 H NMR (DMSO-d6, 300 MHz) delta2.10 (s, 3H), 5.11 (brs, 2H), 6.95 (dd, J=8.14 Hz, 1H), 7.26 (t, J=2.72 Hz, 1H); MS (CI/NH3) m/z: 127 (M+H)+, 144 (M+NH4)+.
  • 5
  • [ 19346-46-4 ]
  • Sodium 1-cyanoprop-1-ene 2-oxide [ No CAS ]
  • [ 744209-96-9 ]
YieldReaction ConditionsOperation in experiment
44% Sodium hydride (1.54 g of 60 % dispersion in oil, 38.5 mmol, 2 eq) was added to a solution of cyanoacetone sodium salt (2.5 g, 23 mmol, 1.2 eq) in DMF (40 mL) at RT. The mixture was stirred for 15 min, then a solution of 2-fluoro-3-methyl-5- nitropyridine (3.0 g, 19.2 mmol, 1.0 eq) in 10 mL DMF was added dropwise. The reaction mixture was stirred at RT for 6 hr. The reaction was quenched with 5 g ice, followed by 150 mL water and 10 mL acetic acid. The mixture was extracted with ethyl acetate, then the combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography using 30% ethyl acetate in hexanes as eluent, providing 11 a (1.85 g, 44 % yield) as an orange oil.
44% Sodium hydride (1.54 g of 60 % dispersion in oil, 38.5 mmol, 2 eq) was added to a solution of cyanoacetone sodium salt (2.5 g, 23 mmol, 1.2 eq) in DMF (40 mL) at rt. The mixture was stirred for 15 min, then a solution of 2-fluoro-3- methyl-5-nitropyridine (3.0 g, 19.2 mmol, 1.0 eq) in 10 mL DMF was added dropwise. The reaction mixture was stirred at rt for 6 h. The reaction was quenched with 5 g ice, followed by 150 mL water and 10 mL acetic acid. The mixture was extracted with ethyl acetate, then the combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography using 30% ethyl acetate in hexanes as eluant, providing 13a (1.85 g, 44 % yield) as an orange oil.
  • 6
  • [ 19346-46-4 ]
  • [ 100-63-0 ]
  • 3-methyl-5-nitro-2-(2-phenylhydrazinyl)pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
In methanol; at 20 - 60℃; General procedure: The synthesis of 3-methyl-5-nitro-2-(2-phenylhydrazinyl)pyridine (PH5N3M) was performed in the following way: 0.01 mol of <strong>[19346-46-4]2-fluoro-3-methyl-5-nitropyridine</strong> was dissolved in10 cm3 of methanol and 0.02 mol of phenylhydrazine was added to this solution. The obtained mixture was heated for 1-2 min at 60 C and left at room temperature for 24 h. Next, the solvent was distilled off under reduced pressure and the residue was extracted with hot chloroform. Insoluble hydrofluoride phenylhydrazine was filtered and washed with warm chloroform.
  • 7
  • [ 19346-46-4 ]
  • 2,2'-(5-phenoxy-1,3-phenylene)bis(oxy)bis(3-methyl-5-nitropyridine) [ No CAS ]
  • 8
  • [ 19346-46-4 ]
  • 6,6'-(5-phenoxy-1,3-phenylene)bis(oxy)bis(5-methylpyridin-3-amine) [ No CAS ]
  • 9
  • [ 19346-46-4 ]
  • 6,6'-(5-phenoxy-1,3-phenylene)bis(oxy)bis(5-methyl-3-pyridinol) [ No CAS ]
  • 10
  • [ 19346-46-4 ]
  • [ 106120-04-1 ]
  • 2,2'-(5-bromo-1,3-phenylene)bis(oxy)bis(3-methyl-5-nitropyridine) [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; at 20℃; for 16h; Potassium Carbonate was added to a solution of 5-bromobenzene-1,3-diol and <strong>[19346-46-4]2-fluoro-3-methyl-5-nitropyridine</strong> and stirred at room temperature for 16 hours. Reaction mixture was diluted with ice cold water and extracted with ethyl acetate. The combined organic layer was dried with sodium sulphate and evaporated under reduced pressure to obtain 2,2'-(5-bromo-1,3-phenylene)bis(oxy)bis(3-methyl-5-nitropyridine).
  • 11
  • [ 108-73-6 ]
  • [ 19346-46-4 ]
  • 1,3,5-tris(3-methyl-5-nitropyridin-2-yloxy)benzene [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 16h; Potassium Carbonate was added to a solution of benzene-1, 3, 5-triol and 2-fluoro-3, 6-dimethyl-5-nitropyridine in dimethyl form amide and the reaction mixture was stirred at room temperature for 16 h. Reaction mixture was diluted with ice cold water and extracted with ethyl acetate. The combined organic layer was dried with sodium sulphate and evaporated under reduced pressure to obtain 1,3,5-tris(3-methyl-5-nitropyridin-2-yloxy)benzene.
 

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