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Structure of 25462-85-5

Chemical Structure| 25462-85-5

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Product Details of [ 25462-85-5 ]

CAS No. :25462-85-5
Formula : C7H6ClNO2
M.W : 171.58
SMILES Code : O=C(O)C1=CC(C)=NC(Cl)=C1
MDL No. :MFCD00052830
InChI Key :ZGZMEKHQIZSZOH-UHFFFAOYSA-N
Pubchem ID :141209

Safety of [ 25462-85-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H317-H319-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 25462-85-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 41.17
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.

1.3
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

1.74
Log Po/w (WLOGP)?

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

1.74
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.

-0.18
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

1.82
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.28

Water Solubility

Log S (ESOL):?

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

-2.34
Solubility 0.789 mg/ml ; 0.0046 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.

-2.41
Solubility 0.666 mg/ml ; 0.00388 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

-2.4
Solubility 0.688 mg/ml ; 0.00401 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.

-6.11 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)

1.62

Application In Synthesis of [ 25462-85-5 ]

* 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 [ 25462-85-5 ]

[ 25462-85-5 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 25462-85-5 ]
  • [ 64-17-5 ]
  • [ 3998-88-7 ]
YieldReaction ConditionsOperation in experiment
86% With sulfuric acid; at 0 - 80℃; Step 1: Ethyl 2-chloro-6-methylisonicotinate (97). To a stirred solution of 96 (7.0 g, 40.79 mmol) in ethanol (70 mL) was added conc H2SO4 (2 mL) at 0 C. dropwise followed by heating at 80 C. for 12 h. The reaction mixture was cooled to room temperature and concentrated in vacuo. The resulting residue was diluted with ethyl acetate and washed with water, sodium bicarbonate solution and sat. NaCl. The organic layer was dried over anhydrous Na2SO4 and concentrated to afford 97 (7 g, 86%) as a white solid.
a) A solution of 2-chloro-6-methylisonicotinic acid (15.5 g, 90.3 mmol, 1 equivalent) in EtOH (200 ml.) and a few drops of concentrated sulfuric acid is stirred at 75C for 24 h. The solvent is evaporated and the residue is dissolved in ethyl acetate (200 ml.) and washed with a solution of sat. aq. NaHCO3 (70 ml.) and water (2x70 ml_). The org. extract is dried over MgSO4, filtered and evaporated to give 2-chloro-6-methylisonicotinic acid ethyl ester (16.3 g) as a pink powder; LC-MS: tR = 0.92 min, [M+1]+ = 200.17.
A solution of 2-chloro-6-methylisonicotinic acid (15.5 g, 90.3 mmol, 1 eq.) in ethanol (200 mL) and a few drops of concentrated sulfuric acid is stirred at 75C for24 h. The solvent is evaporated and the residue is dissolved in ethyl acetate (200 mL) and washed with a solution of sat. aq. NaHCO3 (70 mL) and water (2x70 mL). <n="40"/>The org. extract is dried over MgSO4, filtered and evaporated to give 2-chloro-6- methylisonicotinic acid ethyl ester (16.3 g) as a pink powder; LC-MS: tR = 0.92 min, [M+1]+ = 200.17; A solution of 2-chloro-6-methyl-isonicotinic acid (15.5 g, 90.3 mmol) in ethanol (200 mL) and H2SO4 (0.5 mL) is stirred at 75C for 24 h. The solvent is evaporated and the residue is dissolved in EA (200 mL). The solution is washed with sat. aq. NaHCO3-solution (70 mL) and water (70 mL), dried over MgSO4, filtered, concentrated and dried under HV to give 2-chloro-6-methyl-isonicotinic acid ethyl ester (16.3 g) as a pink powder; LC-MS: tR = 0.92 min; [M+1]+ = 200.17.
A solution of 2-chloro-6-methylisonicotinic acid (15.5 g, 90.3 mmol, 1 equivalent) in EtOH (200 mL) and a few drops of concentrated sulfuric acid is stirred at 75 C. for 24 h. The solvent is evaporated and the residue is dissolved in ethyl acetate (200 mL) and washed with a solution of sat. aq. NaHCO3 (70 mL) and water (2×70 mL). The org. extract is dried over MgSO4, filtered and evaporated to give 2-chloro-6-methylisonicotinic acid ethyl ester (16.3 g) as a pink powder; LC-MS: tR=0.92 min, [M+1]+=200.17.
a) To a solution of 2-chloro-6-methylisonicotinic acid (50 g, 291.4 mmol) in ethanol (750 mL), a few drops of concentrated sulfuric acid are added and the mixture is stirred at 75 C. for 24 h. The solvent is evaporated and the residue is dissolved in ethyl acetate (300 mL) and washed with a solution of sat. aq. NaHCO3 (100 mL) followed with brine (2*70 mL). The org. extract is dried over MgSO4, filtered and evaporated to give 2-chloro-6-methylisonicotinic acid ethyl ester (54.9 g) as a white solid after recrystallization from heptane; LC-MS: tR=0.92 min, [M+1]+=200.17.
a) Concentrated H2SO4 (1.16 mL, 21.6 mmol) is added dropwise to a suspension of 2-chloro-6-methylpyridine-4-carboxylic acid (11.58 g, 67.49 mmol) in ethanol (100 mL). The reaction mixture is then stirred at 70 C. for 24 h. Sat. NaHCO3 is added slowly to reach pH 8 and the aq. solution is extracted with EA three times. The org. extracts are collected, dried over MgSO4, filtered and evaporated to give 2-chloro-6-methylpyridine-4-carboxylic acid ethyl ester (11.81 g) as an off white solid; LC-MS: tR=0.91 min, [M+H]+=199.93.
With sulfuric acid; In ethanol; at 75℃; for 24h;Product distribution / selectivity; a) A solution of 2-chloro-6-methylisonicotinic acid (15.5 g, 90.3 mmol, 1 eq.) in ethanol (200 mL) and a few drops of concentrated sulfuric acid is stirred at 75 C. for 24 h. The solvent is evaporated and the residue is dissolved in ethyl acetate (200 mL) and washed with a solution of sat. aq. NaHCO3 (70 mL) and water (2*70 mL). The org. extract is dried over MgSO4, filtered and evaporated to give 2-chloro-6-methylisonicotinic acid ethyl ester (16.3 g) as a pink powder; LC-MS: tR=0.92 min, [M+1]+=200.17.
To a solution of 2-chloro-6-methylisonicotinic acid (50 g, 291.4 mmol) in ethanol (750 ml_), a few drops of concentrated sulfuric acid are added and the mixture is stirred at 75C for 24 h. The solvent is evaporated and the residue is dissolved in ethyl acetate (300 ml.) and washed with a solution of sat. aq. NaHCO3 (100 ml.) followed with brine (2x70 ml_). The org. extract is dried over MgSO4, filtered and evaporated to give 2-chloro-6- methylisonicotinic acid ethyl ester (54.9 g) as a white solid after recrystallization from heptane; LC-MS: tR = 0.92 min, [M+1]+ = 200.17.

  • 2
  • [ 25462-85-5 ]
  • [ 3998-88-7 ]
  • 3
  • [ 25462-85-5 ]
  • [ 7664-93-9 ]
  • [ 3998-88-7 ]
YieldReaction ConditionsOperation in experiment
86% In ethanol; dichloromethane; The starting material was prepared as follows: A solution of 2-chloro-6-methyl-4-pyridinecarboxylic acid (2 g, 12 mmol) in ethanol (100 ml) and concentrated sulphuric acid (10 ml) was heated at reflux for 2 hours. The volatiles were removed by evaporation and the residue was dissolved in methylene chloride. The solution was washed with a saturated aqueous sodium hydrogen carbonate solution and brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluding with ethyl acetate/petroleum ether (1/9) to give ethyl 2-chloro-6-methyl-4-pyridinecarboxylate (2 g, 86%). 1 H NMR Spectrum: (CDCl3) 1.41(t, 3H); 2.6(s, 3H); 4.40(q, 2H); 7.63(s, 1H); 7.69(s, 1H) MS - ESI: 200 [MH]+ Elemental Analysis: Found C 54.4 H 5.3 N 7.0 C9 H10 NO2 Cl Requires C 54.1 H 5.0 N 7.0%
  • 4
  • [ 25462-85-5 ]
  • [ 22123-14-4 ]
 

Historical Records

Technical Information

Categories

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