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Chemical Structure| 393-53-3 Chemical Structure| 393-53-3

Structure of 393-53-3

Chemical Structure| 393-53-3

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Product Details of [ 393-53-3 ]

CAS No. :393-53-3
Formula : C6H4FNO2
M.W : 141.10
SMILES Code : C1=CN=CC(=C1C(=O)O)F
MDL No. :MFCD03789251
Boiling Point : No data available
InChI Key :POLXLLIQWDBJMD-UHFFFAOYSA-N
Pubchem ID :345361

Safety of [ 393-53-3 ]

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

Computational Chemistry of [ 393-53-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 31.15
TPSA ?

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

50.19 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

0.48
Log Po/w (WLOGP)?

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

1.34
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.

-0.69
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

1.17
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.61

Water Solubility

Log S (ESOL):?

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

-1.4
Solubility 5.68 mg/ml ; 0.0403 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.

-1.1
Solubility 11.1 mg/ml ; 0.0788 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

-1.65
Solubility 3.15 mg/ml ; 0.0223 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.

-6.82 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

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)

1.27

Application In Synthesis of [ 393-53-3 ]

* 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 [ 393-53-3 ]

[ 393-53-3 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 399-88-2 ]
  • [ 393-53-3 ]
  • 2
  • [ 393-53-3 ]
  • [ 27757-86-4 ]
  • 3-[(3-thienylmethyl)amino]-4-pyridinecarboxylic acid hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
24% Example 117: 3-l(3-thienylmethyl)aminol-4-pyridinecarboxylic acid hydrochloride To a mixture of 3-fluoro-4-pyridinecarboxylic acid (200 mg, 1.417 mmol) and N-ethyl-N-(1-methylethyl)-2-propanamine (619 p1, 3.54 mmol) was added <strong>[27757-86-4](3-thienylmethyl)amine</strong> (198 mg, 1 .701mmol). The reaction mixture was heated using a microwave 160C for 4hr then diluted with DMSO (4ml) and purified by MDAP (High pH modifier, Method E) to give the free base compound as a whitesolid (83 mg). This was dissolved in 1 ,4-Dioxane (3 ml) then 2N HCI in ether (178 p1, 0.356 mmol)was added and the resulting solution concentrated under reduced pressure to give the title compoundas a yellow solid (92 mg, 24%)LCMS (Method B): Rt = 0.55 mins, MH+ = 235.1
  • 3
  • [ 393-53-3 ]
  • [ 74-89-5 ]
  • [ 1461602-59-4 ]
YieldReaction ConditionsOperation in experiment
93% In 1,4-dioxane; water; at 140℃; for 14.0h; 3-Fluoroisonicotinic acid (3.00 g, 21.3 mmol) was dissolved in dioxane (6 mL) and 30% aqueous methylamine solution (22.0 g, 213 mmol) was added. The reaction solution was heated to 140C and stirred for 14 hours. Conc. hydrochloric acid (12 N, 3 mL) was added and the pH was adjusted to 3, filtered and the filter cake was dried to give 3-(methylamino)isonicotinic acid (3.00 g, as a yellow solid) with a yield of 93%. 1H NMR: (400 MHz, DMSO-d6) delta 8.46(br, 1H), 7.89(s, 1H), 7.69(d, J = 5.2 Hz, 1H), 7.50(d, J = 5.2 Hz, 1H), 2.80(s, 3H).
93% In 1,4-dioxane; water; at 140℃; for 14.0h; 3-Fluoroisonicotinic acid (3.00 g, 21.3 mmol) was dissolved in dioxane (6 mL), and then 30% methylamine aqueous solution (22.0 g, 213 mmol) was added. The reaction solution was heated to 140 C. and then stirred for 14 hours. Concentrated hydrochloric acid (12N, 3 mL) was added to adjust the pH value to pH=3, followed by filtration. The filter cake was dried to give 3-(methylamino)isonicotinic acid (3.00 g, yellow solid) with a yield of 93%. 1H NMR: (400 MHz, DMSO-d6) delta8.46 (s, 1H), 7.89 (s, 1H), 7.69 (d, J=4.8 Hz, 1H), 7.50 (d, J=4.8 Hz, 1H), 2.80 (s, 3H).
42% In 1,4-dioxane; water; at 125℃; for 9.5h;Microwave irradiation; Example 153: 3-(methylamino)-4-pyridinecarboxylic acid Methylamine (0.321 mL,3.90 mmol, 40% solution in water) was added to a 3-fluoro-4- pyridinecarboxylic acid (250 mg, 1 .772 mmol) and 1 ,4-Dioxane (0.3 ml) and the mixture heated using a microwave to 125 C for 1.5 hr then 2 hr and finally an additional 6 hr. The mixture was allowed tocoolthen concentrated by evaporation. Water (10 ml) was added then the mixture acidifed to pH 3 using 37% HCI. The resulting bright yellow precipitate was filtered then washed with water (10 ml) to give the title compound as a yellow solid, 114 mg (42%).1H NMR (400 MHz, DMSO-S6) 8.2oppm (1H, 5), 7.84ppm (1H, d), 7.Ssppm (1H, d), 2.93ppm (3H, 5).
  • 4
  • [ 51586-20-0 ]
  • [ 393-53-3 ]
  • 3-((2,3-dimethylbenzyl)amino)isonicotinic acid [ No CAS ]
  • 5
  • [ 393-53-3 ]
  • [ 27757-86-4 ]
  • 3-((thiophen-3-ylmethyl)amino)isonicotinic acid [ No CAS ]
 

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Technical Information

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