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Structure of 403-24-7

Chemical Structure| 403-24-7

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Product Details of [ 403-24-7 ]

CAS No. :403-24-7
Formula : C7H4FNO4
M.W : 185.11
SMILES Code : O=C(O)C1=CC=C([N+]([O-])=O)C=C1F
MDL No. :MFCD00275565
InChI Key :MMWFMFZFCKADEL-UHFFFAOYSA-N
Pubchem ID :302679

Safety of [ 403-24-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 403-24-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 2
Num. H-bond acceptors 5.0
Num. H-bond donors 1.0
Molar Refractivity 42.18
TPSA ?

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

83.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.73
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

1.8
Log Po/w (WLOGP)?

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

1.85
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.

0.94
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

-0.48
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.97

Water Solubility

Log S (ESOL):?

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

-2.33
Solubility 0.863 mg/ml ; 0.00466 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.

-3.16
Solubility 0.127 mg/ml ; 0.000685 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

-1.43
Solubility 6.85 mg/ml ; 0.037 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

No
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.

-6.15 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.

0.56

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

2.0 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)

1.61

Application In Synthesis of [ 403-24-7 ]

* 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 [ 403-24-7 ]

[ 403-24-7 ] Synthesis Path-Downstream   1~4

  • 2
  • [ 403-24-7 ]
  • [ 660432-43-9 ]
YieldReaction ConditionsOperation in experiment
43.3 g of 2-fluoro-4-nitrobenzoic acid was dissolved in 600 ml of dimethylformamide, and 1,1'-carbodiimide was added to it, and stirred at room temperature for 2 hours. 11.1 g of sodium borohydride was added thereto, and further stirred for 30 minutes. Aqueous saturated ammonium chloride solution was added to it, 800 ml of water was added thereto, extracted wit 1.2 liters of ethyl acetate, and the organic layer was washed with saturated saline water. The solvent was evaporated away under reduced pressure, the residue was again diluted with ethyl acetate, and the organic layer was washed with water and saturated saline water. This was dried with anhydrous sodium sulfate, and the solvent was evaporated away to obtain 32.7 g of a brown oil. The obtained oil was dissolved in 200 ml of dimethyl sulfoxide and 60 ml of triethylamine, and 88.7 g of sulfur trioxide/pyridine complex was gradually added to it, and stirred at room temperature for 2 hours. This was diluted with ethyl acetate, and the organic layer was washed with water, aqueous 0.1 N hydrochloric acid solution and saturated saline water. The solvent was evaporated away under reduced pressure, and the residue was purified through silica gel column chromatography (developing solvent: hexane/ethyl acetate) and through crystallization (methanol/diethyl ether) to obtain 14.0 g of the entitled compound as an orange solid.
With lithium aluminium tetrahydride; In diethyl ether; at 0℃; for 0.75h;Reflux; General procedure: To a stirred suspension of LiAlH4 (3.0mmol) in ether was added dropwise a solution of 21 in ether at 0C over 15min. The mixture was refluxed for 30min, then the reaction cooled to 0C and quenched with 1N HCl. The precipitate was filtered off and washed with ether. The combined filtrate was dried over MgSO4, filtered and concentrated in vacuo. The residue was puried by column chromatography on silica gel to afford the desired product.
  • 3
  • [ 403-24-7 ]
  • [ 140645-23-4 ]
  • C18H24FN3O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In dichloromethane; at 20 - 40℃; General procedure: HATU (1.2 equiv) and DIEA (1.5 equiv) were added to a solutionof 2-fluoro-4-nitrobenzoic acid (1 equiv) and R6-NH2 (1 equiv) inCH2Cl2 at rt. The resulting mixture was heated to 25e40 C andstirred until the reaction was complete. The mixture was dilutedwith ethyl acetate, and the organic layer was washed with saline,dried over anhydrous Na2SO4 and filtered. The filtrate wasconcentrated and purified using chromatography to yield the intermediates33a-g. Intermediates 33a-g (1 equiv) were dissolved inethanol, and Pd/C (0.1 equiv)was added. The flask was flushed withH2 and stirred for 6 h at 40 C. The reaction mixture was filteredthrough a Celite pad and the filtrate was concentrated to dryness,yielding intermediates 34a-g.
  • 4
  • [ 403-24-7 ]
  • [ 140645-24-5 ]
  • C18H24FN3O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In dichloromethane; at 20 - 40℃; General procedure: HATU (1.2 equiv) and DIEA (1.5 equiv) were added to a solutionof 2-fluoro-4-nitrobenzoic acid (1 equiv) and R6-NH2 (1 equiv) inCH2Cl2 at rt. The resulting mixture was heated to 25e40 C andstirred until the reaction was complete. The mixture was dilutedwith ethyl acetate, and the organic layer was washed with saline,dried over anhydrous Na2SO4 and filtered. The filtrate wasconcentrated and purified using chromatography to yield the intermediates33a-g. Intermediates 33a-g (1 equiv) were dissolved inethanol, and Pd/C (0.1 equiv)was added. The flask was flushed withH2 and stirred for 6 h at 40 C. The reaction mixture was filteredthrough a Celite pad and the filtrate was concentrated to dryness,yielding intermediates 34a-g.
 

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