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Chemical Structure| 73406-50-5 Chemical Structure| 73406-50-5

Structure of Ethyl 3-hydroxypicolinate
CAS No.: 73406-50-5

Chemical Structure| 73406-50-5

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Product Details of [ 73406-50-5 ]

CAS No. :73406-50-5
Formula : C8H9NO3
M.W : 167.16
SMILES Code : O=C(OCC)C1=NC=CC=C1O
MDL No. :MFCD11656384
InChI Key :NNYREQBXDUEBDD-UHFFFAOYSA-N
Pubchem ID :15080989

Safety of [ 73406-50-5 ]

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

Computational Chemistry of [ 73406-50-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 3
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 42.35
TPSA ?

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

59.42 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.73
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

1.99
Log Po/w (WLOGP)?

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

0.96
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.

0.08
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

1.04
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.16

Water Solubility

Log S (ESOL):?

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

-2.3
Solubility 0.834 mg/ml ; 0.00499 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.

-2.86
Solubility 0.229 mg/ml ; 0.00137 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

-1.92
Solubility 1.99 mg/ml ; 0.0119 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.

-5.91 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)

1.74

Application In Synthesis of [ 73406-50-5 ]

* 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.

  • Upstream synthesis route of [ 73406-50-5 ]

[ 73406-50-5 ] Synthesis Path-Upstream   1~7

  • 1
  • [ 874-24-8 ]
  • [ 64-17-5 ]
  • [ 73406-50-5 ]
YieldReaction ConditionsOperation in experiment
73% With sulfuric acid In toluene at 95℃; for 72 h; Heating / reflux To 3-hydroxypyridine-2-carboxylic acid (25 g, 179.5 mmol) in a 1 L dried flask was added 400 mL ethanol and 100 mL toluene followed by the addition of 10 mL sulfuric acid. The mixture was heated at reflux (95° C.) for 3 days. After cooling to rt, the mixture was concentrated to 1/4 of its volume, and diluted with 600 mL ethyl acetate and 200 mL water. The aqueous layer was extracted with 200 mL ethyl acetate, and the combined organic layers were washed with sat NaHCO3 (3.x.200 mL), brine, and dried over Na2SO4. The solid was filtered off and the solvent was concentrated under reduced pressure to give 21.9 g of ethyl 3-hydroxypyridine-2-carboxylate (73percent), which was used in the next step without purification. This ester (21.9 g, 131 mmol) was dissolved in pyridine and cooled to -40° C., followed by addition of trifluoromethanesulfonic anhydride (48 g, 170 mmol). The reaction mixture was then warmed to 0° C. for 30 min, and then warmed to rt for another 30 min. Water (100 mL) was added to quench the reaction. The mixture was extracted with ethyl acetate (3.x.200 mL), and the combined organic layers were washed with sat sodium bicarbonate (200 mL), water (200 mL), brine (200 mL), and dried over sodium sulfate. The solid was filtered off, and the solvent was removed under reduced pressure to give 39 g (99percent) of desired product, which was used in the next step without further purification. 1H NMR (300 MHz, CD2Cl2) δ 8.73 (dd, 1H), 7.72 (dd, 1H), 7.62 (dd, 1H), 4.46 (q, 2H), 1.42 (t, 3H).
70% With sulfuric acid In toluene at 78℃; for 60 h; Dean-Stark A solution of 3-hydroxypicolinic acid (2.50 g, 18.0 mmol) in EtCH (60 mL) and toluene (20 mL) was treated with conc. H2S04 (1 mL) and stirred under reflux for 60 h withazeotropic removal of water via Dean-Stark trap. The solvent was evaporated, the residue was dissolved in water (50 mL) and carefully basified with a sat. NaHCO3 solution, upon which a white precipitate appeared. The mixture was diluted with EtOAc (30 mL) and the aqueous layer was extracted three times with EtOAc (3 x 20 mL). The combined organic layers were dried over anhydrous Mg504, filtered and evaporated to giveethyl 3-hydroxypicolinate (2.10 g, 70percent) as a colorless liquid.1H NMR (400 MHz, Chloroform-o) 6 = 10.78 (s, 1H, OH), 8.30 (dd, J= 4.2, 1.5 Hz, 1H,H-Ar), 7.47 — 7.34 (m, 2H, H-Ar), 4.54 (q, J= 7.1 Hz, 2H, O-CH2CH3), 1.49 (t, J= 7.1Hz, 3H, O-CH2CH3) ppm.MS (ESl+, H20/MeCN) mlz(percent): 168.0 (100, [M + H]j.
References: [1] Journal of Heterocyclic Chemistry, 1986, vol. 23, # 3, p. 665 - 668.
[2] Patent: US2005/192294, 2005, A1, . Location in patent: Page/Page column 20-21.
[3] Patent: WO2018/229193, 2018, A1, . Location in patent: Page/Page column 138.
[4] Journal of Medicinal Chemistry, 2003, vol. 46, # 22, p. 4702 - 4713.
[5] Patent: WO2005/42538, 2005, A1, . Location in patent: Page/Page column 15; 16.
[6] MedChemComm, 2015, vol. 6, # 10, p. 1767 - 1772.
  • 2
  • [ 874-24-8 ]
  • [ 73406-50-5 ]
References: [1] Journal of the Chemical Society, 1958, p. 4466,4468.
[2] Patent: US6316464, 2001, B1, .
  • 3
  • [ 164254-26-6 ]
  • [ 73406-50-5 ]
  • [ 164254-30-2 ]
References: [1] Journal of Organic Chemistry, 1994, vol. 59, # 18, p. 5347 - 5357.
  • 4
  • [ 122060-92-8 ]
  • [ 73406-50-5 ]
References: [1] Journal of Organic Chemistry, 1994, vol. 59, # 18, p. 5347 - 5357.
  • 5
  • [ 164254-29-9 ]
  • [ 73406-50-5 ]
References: [1] Journal of Organic Chemistry, 1994, vol. 59, # 18, p. 5347 - 5357.
  • 6
  • [ 762-42-5 ]
  • [ 164254-26-6 ]
  • [ 73406-50-5 ]
  • [ 164254-30-2 ]
References: [1] Journal of Organic Chemistry, 1994, vol. 59, # 18, p. 5347 - 5357.
  • 7
  • [ 73406-50-5 ]
  • [ 13210-29-2 ]
References: [1] Journal of Heterocyclic Chemistry, 1986, vol. 23, # 3, p. 665 - 668.
 

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