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Structure of 500577-99-1

Chemical Structure| 500577-99-1

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Product Details of [ 500577-99-1 ]

CAS No. :500577-99-1
Formula : C7H5F2NO2
M.W : 173.12
SMILES Code : NC1=C(F)C=C(C=C1F)C(O)=O
MDL No. :MFCD03407440
Boiling Point : No data available
InChI Key :MJHZRTJMDQYAHN-UHFFFAOYSA-N
Pubchem ID :282133

Safety of [ 500577-99-1 ]

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

Computational Chemistry of [ 500577-99-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 4.0
Num. H-bond donors 2.0
Molar Refractivity 37.72
TPSA ?

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

63.32 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.98
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

0.97
Log Po/w (WLOGP)?

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

2.09
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.

0.75
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

1.36
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.23

Water Solubility

Log S (ESOL):?

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

-1.83
Solubility 2.57 mg/ml ; 0.0148 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-1.89
Solubility 2.24 mg/ml ; 0.013 mol/l
Class?

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

Very 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

-1.97
Solubility 1.87 mg/ml ; 0.0108 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.

-6.67 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

1.0 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)

1.17

Application In Synthesis of [ 500577-99-1 ]

* 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.

  • Upstream synthesis route of [ 500577-99-1 ]

[ 500577-99-1 ] Synthesis Path-Upstream   1~2

  • 1
  • [ 110301-23-0 ]
  • [ 500577-99-1 ]
YieldReaction ConditionsOperation in experiment
84% at 110℃; for 16 h; 4-amino-3,5-difluorobenzonitrile (354.3 mg, 2.3 mmol) was suspended in 1M aqueous sodium hydroxide (12 mL) and the resulting suspension was heated at 110 °C for 16 h. After cooling, the mixture was washed with ether. The aqueous phase was acidified to pH = 2 with 10percent KHS04/Na2S04 buffer and extracted with EtOAc (2X). The combined EtOAc extracts were washed with water, and then brine, dried over anhydrous sodium sulfate and concentrated in vacuo to provide 4-amino-3,5-difluorobenzoic acid (335 mg, 84percent yield) as a yellow solid. 1H NMR (300 MHz, Chloroform-d) δ 7.66 - 7.58 (m, 2H).
71.4% for 18 h; Reflux Step S2: 25 g of 2,6-difluoro-4-cyanoaniline is dissolved in 800 mL of 1 M sodium hydroxide solution.After refluxing for 18 h, the reaction was completed by TLC thin layer chromatography and cooled to room temperature.Adjust the system to pH=8 with 1N hydrochloric acid, precipitate a large amount of solid, and filter by suction.The solid was dissolved in 500 mL of ethyl acetate and dried over anhydrous sodium sulfate (20 g).The product was concentrated to give a pale yellow solid (20.2 g).The yield was 71.4percent.
References: [1] Journal of Materials Chemistry C, 2016, vol. 4, # 23, p. 5326 - 5333.
[2] Organic and Biomolecular Chemistry, 2019, vol. 17, # 7, p. 1827 - 1833.
[3] ACS Medicinal Chemistry Letters, 2018, vol. 9, # 3, p. 250 - 255.
[4] Patent: WO2018/136935, 2018, A1, . Location in patent: Paragraph 00408.
[5] Bioconjugate Chemistry, 2018, vol. 29, # 2, p. 324 - 334.
[6] Patent: CN108947782, 2018, A, . Location in patent: Paragraph 0019; 0023; 0030; 0037; 0042; 0044.
[7] Journal of the American Chemical Society, 2012, vol. 134, # 51, p. 20597 - 20600.
  • 2
  • [ 67567-26-4 ]
  • [ 500577-99-1 ]
References: [1] Bioconjugate Chemistry, 2018, vol. 29, # 2, p. 324 - 334.
[2] ACS Medicinal Chemistry Letters, 2018, vol. 9, # 3, p. 250 - 255.
[3] Patent: WO2018/136935, 2018, A1, .
[4] Patent: CN108947782, 2018, A, .
[5] Organic and Biomolecular Chemistry, 2019, vol. 17, # 7, p. 1827 - 1833.
 

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