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Structure of 140675-43-0

Chemical Structure| 140675-43-0

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Product Details of [ 140675-43-0 ]

CAS No. :140675-43-0
Formula : C7H4FNO
M.W : 137.11
SMILES Code : FC1=C(C#N)C(=CC=C1)O
MDL No. :MFCD03428592
InChI Key :YEBHNFDMNFHZFF-UHFFFAOYSA-N
Pubchem ID :2783216

Safety of [ 140675-43-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H312-H319-H332
Precautionary Statements:P280-P310-P305+P351+P338

Computational Chemistry of [ 140675-43-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 33.14
TPSA ?

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

44.02 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.38
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

1.94
Log Po/w (WLOGP)?

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

1.82
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.

1.22
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

1.74
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.62

Water Solubility

Log S (ESOL):?

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

-2.36
Solubility 0.604 mg/ml ; 0.0044 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.

-2.49
Solubility 0.445 mg/ml ; 0.00325 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

-2.16
Solubility 0.955 mg/ml ; 0.00697 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

Yes
Log Kp (skin permeation)?

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

-5.76 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)

1.34

Application In Synthesis of [ 140675-43-0 ]

* 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 [ 140675-43-0 ]

[ 140675-43-0 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 94088-46-7 ]
  • [ 140675-43-0 ]
YieldReaction ConditionsOperation in experiment
87% With pyridine hydrochloride; at 190℃; for 5h; 1.6: 2-Fluoro-6-hvdroxybenzo?itrile (analogous to WO 99/14187):151 g (1 mol) of <strong>[94088-46-7]2-fluoro-6-methoxybenzonitrile</strong> and 346.5 g (3 mol) of pyridinium hy¬ drochloride were introduced into a 2 I flask and then slowly heated to 1900C under a protective gas atmosphere and then stirred at this temperature for 5 h. The mixture was cooled by slowly stirring to room temperature overnight. Then 1000 ml of water were added, and the mixture was heated to 8O0C. After adding 1000 ml of methyl tert.-butyl ether, the phases were separated and the aqueous phase was back-extracted twice with 500 ml of methyl tert.-butyl ether. The combined methyl tert.-butyl ether phases were washed once with 800 ml of 10% strength aqueous sodium hydroxide solution and once with 400 ml of water. The two aqueous phases were combined, adjusted to pH 2 with concentrated hydrochloric acid and washed three times with 500 ml of methylene chloride. Then, the combined organic phases were washed once with 10% strength hydrochloric acid. The organic phase was dried over sodium sulfate. Finally, the solvent was distilled off in vacuo. Yield: 12O g (87% of theory) of the desired product of purity >99% according to GC.1H NMR (in D6 dimethylsulfoxide): delta = 6.85 ppm (m, 2H, arom. H), 7.55 ppm (q, 1H, arom. H), 11.7 ppm (s, 1H1 OH).
With pyridine hydrochloride; at 20 - 190℃; 1.2. 2-Fluoro-6-hydroxybenzonitrile:; 151 g (1 mol) of <strong>[94088-46-7]2-fluoro-6-methoxybenzonitrile</strong> and 346.5 g (3 mol) of pyridinium hydrochloride have been introduced into a 2 I flask and then slowly heated to 190C under a protective gas atmosphere and then stirred at this temperature for 5 h. The mixture has been cooled with slow stirring to room temperature overnight. Then 1000 ml of water have been added, and the mixture has been heated to 80C. After adding 1000 ml of methyl tert-butyl ether, the phases have been are separated and the aqueous phase has been back-extracted twice with 500 ml of methyl tert-butyl ether. The combined methyl tert-butyl ether phases have been washed once with 800 ml of 10% strength NaOH and once with 400 ml of water. The two aqueous phases have been combined, adjusted to pH 2 with concentrated hydrochloric acid and washed three times with 500 ml of methylene chloride. Then, the combined organic phases <n="246"/>have been washed once with 10% strength hydrochloric acid. The organic phase has been dried over sodium sulfate. Finally, the solvent has been distilled off in vacuo to give 120 g (870 mmol) of the desired product.
  • 2
  • [ 74-96-4 ]
  • [ 140675-43-0 ]
  • [ 119584-73-5 ]
YieldReaction ConditionsOperation in experiment
67% With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere; a) 2-Ethoxy-6-fluorobenzonitrile I52 A mixture of 2-fluoro-6-hydroxybenzonitrile (2.0 g, 14.6 mmol), K2CO3 (6.04 g, 43.8 mmol) and bromoethane (2.38 g, 21.9 mmol) in DMF (4 ml.) was stirred at RT under N2 overnight. The mixture was diluted with EtOAc (300 ml_), washed with water (100 ml. x 5), brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (Pet. ether/EtOAc = 100/1 to 5/1) to give the title compound (1.6 g, 67%) as a white solid. LCMS-E: Rt5.24 min; m/z 166.1 [M+H]+.
 

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