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Chemical Structure| 5027-65-6 Chemical Structure| 5027-65-6

Structure of 5027-65-6

Chemical Structure| 5027-65-6

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Product Details of [ 5027-65-6 ]

CAS No. :5027-65-6
Formula : C8H7NO4
M.W : 181.15
SMILES Code : O=C(O)C1=CN=CC(C(OC)=O)=C1
MDL No. :MFCD07367955
Boiling Point : No data available
InChI Key :GUXKBDHITFXEJG-UHFFFAOYSA-N
Pubchem ID :19881638

Safety of [ 5027-65-6 ]

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

Computational Chemistry of [ 5027-65-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 3
Num. H-bond acceptors 5.0
Num. H-bond donors 1.0
Molar Refractivity 42.48
TPSA ?

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

76.49 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.17
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

0.23
Log Po/w (WLOGP)?

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

0.57
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.

-1.13
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

0.6
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.29

Water Solubility

Log S (ESOL):?

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

-1.25
Solubility 10.2 mg/ml ; 0.056 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.

-1.4
Solubility 7.28 mg/ml ; 0.0402 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

-1.47
Solubility 6.08 mg/ml ; 0.0336 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.

-7.24 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)

1.51

Application In Synthesis of [ 5027-65-6 ]

* 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 [ 5027-65-6 ]

[ 5027-65-6 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 4591-55-3 ]
  • [ 5027-65-6 ]
YieldReaction ConditionsOperation in experiment
With potassium hydroxide; In methanol; at 20℃; for 16h; A solution of potassium hydroxide (1.30 g, 23.2 mmol.) in MeOH (25 mL) was added carefully to a solution of <strong>[4591-55-3]pyridine-3,5-dicarboxylic acid dimethyl ester</strong> (4.53 g, 23.2 mmol.) in MeOH (50 mL). The reaction mixture was stirred at room temperature for 16 h. Diethyl ether (600 mL) was added, the reaction was filtered, and the precipitate was suspended in MeOH (20 mL). Concentrated HCl (75 mL) was added followed by ditheyl ether (120 mL). Filtration of the resulting mixture yielded the ester/acid as the hydrochloride salt (3.23 g, 14.9 mmol., 64%) which was used without further purification. The ester/acid (1.0 g, 4.61 mmol.) was suspended in toluene and thionyl chloride (1.33 mL, 18.44 mmol.) was added. The reaction was heated to reflux for 4 h, then concentrated without heating the reaction flask above 50 C. The crude acid chloride was dried in vacuo and used directly in the next step. Lithium tri-tertbutoxyaluminum hydride (1M, 3.58 mL, 3.58 mmol.) was added to a solution of acid chloride (841 mg, 3.58 mmol.) in THF (10 mL) at -78 C. The reaction was allowed to warm to room temperature, was stirred for 16 h, and was quenched with 1N HCl. The resulting solution was concentrated, was partitioned between ethyl acetate and saturated sodium bicarbonate was extracted with ethyl acetate (3×). The combined organic extracts were dried with MgSO4 and concentrated. The crude alcohol was purified by column chromatography (70% ethyl acetate/hexane) to yield pure product (200 mg, 1.20 mmol., 26%). 1H NMR (DMSO-d6): delta=8.97 (s, 1H), 8.75 (s, 1H), 8.24 (s, 1H), 5.48 (t, J=6 Hz, 1H), 4.62 (d, J=6 Hz, 3H), 3.89 (s, 3H). Calculated mass=165.1, [M+H]+=168. HPLC (method D) rt=3.4 min ( 98%).
  • 2
  • [ 4591-55-3 ]
  • [ 499-81-0 ]
  • [ 5027-65-6 ]
YieldReaction ConditionsOperation in experiment
3,5-<strong>[4591-55-3]dimethyl pyridine-3,5-dicarboxylate</strong> (500 mg, 2.56 mmol) was dissolved in methanol (2 ml_) and 1 M NaOH (2.56 ml_, 2.56 mmol) was slowly added. The resulting yellow solution was stirred for 15 mins at RT, then organic solvent was evaporated and the aqueous residue was acidified to pH 2 and extracted with DCM (4 x). Material detected in aqueous phase, therefore aqueous and organic phase were combined and concentrated affording 5- (methoxycarbonyl)pyridine-3-carboxylic acid (561 mg) as yellow solid. Presence of -10% of starting material and 10% dicarboxylic acid detected. Used as such in the next step.
 

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