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Chemical Structure| 214958-32-4 Chemical Structure| 214958-32-4

Structure of 214958-32-4

Chemical Structure| 214958-32-4

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Product Details of [ 214958-32-4 ]

CAS No. :214958-32-4
Formula : C10H9IN2O2
M.W : 316.10
SMILES Code : CCOC(=O)C1=CN2C=C(I)C=CC2=N1
MDL No. :MFCD02186151
InChI Key :TWJHSMVAYMQRTK-UHFFFAOYSA-N
Pubchem ID :3681971

Safety of [ 214958-32-4 ]

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

Computational Chemistry of [ 214958-32-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 9
Fraction Csp3 0.2
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 64.0
TPSA ?

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

43.6 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.69
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

2.96
Log Po/w (WLOGP)?

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

2.12
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.

1.78
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

2.05
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.32

Water Solubility

Log S (ESOL):?

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

-3.91
Solubility 0.0388 mg/ml ; 0.000123 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.

-3.54
Solubility 0.0915 mg/ml ; 0.000289 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

-3.5
Solubility 0.1 mg/ml ; 0.000318 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

Yes
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

Yes
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

Yes
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.

-6.13 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

0.0
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

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<0.0
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)

2.33

Application In Synthesis of [ 214958-32-4 ]

* 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 [ 214958-32-4 ]

[ 214958-32-4 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 145214-05-7 ]
  • [ 214958-32-4 ]
  • [ 1167626-86-9 ]
YieldReaction ConditionsOperation in experiment
With lithium chloride;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 90℃; for 3.5h;Inert atmosphere; Intermediate 12: 6-(Oxazol-2-yl)imidazo[1,2-α]pyridine-2-carboxylic acid 12.1: Ethyl 6-(oxazol-2-yl)imidazo[1,2-α]pyridine-2-carboxylate 1 g of ethyl 6-iodoimidazo[1,2-α]pyridine-2-carboxylate, 350 mg of tetrakis(triphenyl-phosphine)palladium(0) and 360 mg of lithium chloride are degassed under vacuum and then suspended, under argon, in 15 ml of degassed dioxane. After addition of 5 g of 2-[tri(n-butyl)stannyl]oxazole, the reaction mixture is heated at 90 C. for 3.5 hours, then cooled and diluted and stirred with a mixture of 100 ml of 1M aqueous potassium fluoride solution and 200 ml of ethyl acetate. The aqueous phase is extracted with 200 ml of ethyl acetate and the combined organic phases are washed with aqueous sodium chloride solution and dried over sodium sulphate, filtered and concentrated to dryness under reduced pressure. The residue is chromatographed on silica, elution being carried out with a gradient of ethyl acetate and hexane (from 80/20 to 100/0). The fractions comprising the expected product are combined and concentrated to dryness under reduced pressure to give 530 mg of ethyl 6-(oxazol-2-yl)imidazo[1,2-α]pyridine-2-carboxylate in the form of a yellow powder.1H NMR spectrum (d6-DMSO, δ in ppm): 9.30 (d, J=0.8, 1H), 8.68 (s, 1H), 8.30 (s, 1H), 7.85 (dd, J=1.7, 9.5, 1H), 7.79 (d, J=9.5, 1H), 7.44 (d, J=0.6, 1H), 4.33 (q, J=7.0, 2H), 1.33 (t, J=7.1, 3H).Mass spectrum (APCI): m/z=258 [M+H]+.
With lithium chloride;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 90℃; for 3.5h;Inert atmosphere; 22.1: Ethyl 6-(oxazol-2-yl)imidazo[1,2-a]pyridine-2-carboxylate 1 g of ethyl 6-iodoimidazo[1,2-a]pyridine-2-carboxylate, 350 mg of tetrakis(triphenyl-phosphine)palladium(0) and 360 mg of lithium chloride are degassed under vacuum and then suspended, under argon, in 15 mL of degassed dioxane. After addition of 5 g of <strong>[145214-05-7]2-(tri-n-butylstannyl)oxazole</strong>, the reaction mixture is heated at 90 C. for 3.5 hours and then cooled, diluted and stirred with a mixture of 100 mL of aqueous 1M potassium fluoride solution and 200 mL of ethyl acetate. The aqueous phase is extracted with 200 mL of ethyl acetate and the combined organic phases are washed with brine and dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure. The residue is chromatographed on silica, eluding with a gradient of ethyl acetate and hexane (from 80/20 to 100/0). The fractions containing the expected product are combined and concentrated to dryness under reduced pressure to give 530 mg of ethyl 6-(oxazol-2-yl)imidazo[1,2-a]pyridine-2-carboxylate in the form of a yellow powder. 1H NMR spectrum (DMSO-d6, δ in ppm): 9.30 (d, J=0.8, 1H), 8.68 (s, 1H), 8.30 (s, 1H), 7.85 (dd, J=1.7, 9.5, 1H), 7.79 (d, J=9.5, 1H), 7.44 (d, J=0.6, 1H), 4.33 (q, J=7.0, 2H), 1.33 (t, J=7.1, 3H). Mass spectrum (APCI): m/z=258 [M+H]+.
With lithium chloride;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 90℃; for 3.5h;Inert atmosphere; 1 g of ethyl 6-iodoimidazo[1,2-a]pyridine-2-carboxylate, 350 mg of tetrakis(triphenylphosphine)palladium(0) and 360 mg of lithium chloride are degassed under vacuum and then suspended, under argon, in 15 mL of degassed dioxane. After addition of 5 g of <strong>[145214-05-7]2-(tri-n-butylstannyl)oxazole</strong>, the reaction mixture is heated at 90 C. for 3.5 hours, then cooled, diluted and stirred with a mixture of 100 mL of aqueous 1M potassium fluoride solution and 200 mL of ethyl acetate. The aqueous phase is extracted with 200 mL of ethyl acetate and the combined organic phases are washed with brine and dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure. The residue is chromatographed on silica, eluding with a gradient of ethyl acetate and hexane (from 80/20 to 100/0). The fractions containing the expected product are combined and concentrated to dryness under reduced pressure to give 530 mg of ethyl 6-(oxazol-2-yl)imidazo[1,2-a]pyridine-2-carboxylate in the form of a yellow powder. 1H NMR spectrum (DMSO-d6, δ in ppm): 9.30 (d, J=0.8, 1H), 8.68 (s, 1H), 8.30 (s, 1H), 7.85 (dd, J=1.7, 9.5, 1H), 7.79 (d, J=9.5, 1H), 7.44 (d, J=0.6, 1H), 4.33 (q, J=7.0, 2H), 1.33 (t, J=7.1, 3H). Mass spectrum (APCI): m/z=258 [M+H]+.
 

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