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Chemical Structure| 478169-68-5 Chemical Structure| 478169-68-5

Structure of 478169-68-5

Chemical Structure| 478169-68-5

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Product Details of [ 478169-68-5 ]

CAS No. :478169-68-5
Formula : C13H16O3Si
M.W : 248.35
SMILES Code : O=C(OC)C1=CC=C(C#C[Si](C)(C)C)C(O)=C1
MDL No. :MFCD27959379
InChI Key :IGKWQEJDFVUAME-UHFFFAOYSA-N
Pubchem ID :22481756

Safety of [ 478169-68-5 ]

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

Computational Chemistry of [ 478169-68-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 17
Num. arom. heavy atoms 6
Fraction Csp3 0.31
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 69.97
TPSA ?

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

46.53 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.22
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

3.62
Log Po/w (WLOGP)?

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

2.49
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.

2.7
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

1.41
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.69

Water Solubility

Log S (ESOL):?

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

-3.79
Solubility 0.0403 mg/ml ; 0.000162 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.

-4.28
Solubility 0.0129 mg/ml ; 0.0000519 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately 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

-3.25
Solubility 0.139 mg/ml ; 0.000558 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

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.

-5.24 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

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

2.0 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<2.0
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)

2.59

Application In Synthesis of [ 478169-68-5 ]

* 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 [ 478169-68-5 ]

[ 478169-68-5 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 478169-68-5 ]
  • [ 588703-29-1 ]
  • 2
  • [ 157942-12-6 ]
  • [ 1066-54-2 ]
  • [ 478169-68-5 ]
YieldReaction ConditionsOperation in experiment
91% With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; In tetrahydrofuran; at 50℃; for 4h; Methyl 3-hydroxy-4-iodobenzoate (5.22 g, 18.8 mmol) is combined with trimethylsilylacetylene (3.71 mL, 26.3 mmol), bis(triphenylphosphine)palladium dichloride (386 mg, 0.55 mmol) and cuprous iodide (54 mg, 0.28 mmol) in THF (20 mL)/CHCl3 (40 mL) in a dry flask, under nitrogen. Triethylamine (8.14 mL, 58.4 mmol) is added and the mixture is heated to 50° C. for 4 h. The mixture is diluted with CHCl3 (60 mL), washed with 5percent HCl (2.x.40 mL), dried (MgSO4) and concentrated to a brown oily-solid (8.31 g). The crude material is chromatographed over a standard 90 g Biotage column, eluting with 10percent EtOAc/hexane (1 L) followed by 15percent EtOAc/hexane (1 L). The appropriate fractions are combined and concentrated to afford 4.22 g (91percent) of methyl 3-hydroxy-4-[(trimethylsilyl)ethynyl]benzoate as a yellow solid. HRMS (FAB) calcd for C13H16O3SI+H: 249.0947, found 249.0947 (M+H)+.
4.22 g (91%) With triethanolamine; copper(I) iodide;bis(triphenylphosphine)palladium(II) dichloride; In tetrahydrofuran; hexane; chloroform; ethyl acetate; Methyl 3-hydroxy-4-iodobenzoate (5.22 g, 18.8 mmol) is combined with trimethylsilylacetylene (3.71 mL, 26.3 mmol), bis(triphenylphosphine)palladium dichloride (386 mg, 0.55 mmol) and cuprous iodide (54 mg, 0.28 mmol) in THF (20 mL) CHCl3 (40 mL) in a dry flask, under nitrogen. TEA (8.14 mL<58.4 mmol) is added and the mixture is heated to 50° C. for 4 h. The mixture is diluted with CHCl3 (60 mL), washed with 5percent HCl (2*40 mL), dried over anhydrous MgSO4 and concentrated to a brown paste (8.31 g). The crude material is chromatographed over a standard 90 g Biotage column, eluding with 10percent EtOAc/hexane (1 L) followed by 15percent EtOAc/hexane (1 L). The appropriate fractions are combined and concentrated to afford 4.22 g (91percent) of methyl 3-hydroxy-4-[(trimethylsilyl)ethynyl]benzoate as a yellow solid. HRMS (FAB) calcd for C13H16O3SI+H1: 249.0947, found 249.0947.
4.22 g (91%) With triethanolamine; copper(I) iodide;bis(triphenylphosphine)palladium(II) dichloride; In tetrahydrofuran; hexane; chloroform; ethyl acetate; Methyl-3-hydroxy-4-iodobenzoate (5.22 g, 18.8 mmol) is combined with trimethylsilylacetylene (3.71 mL, 26.3 mmol), bis(triphenylphosphine)palladium dichloride (386 mg, 0.55 mmol) and cuprous iodide (54 mg, 0.28 mmol) in THF (20 mL)/CHCl3 (40 mL) in a dry flask under nitrogen. TEA (8.14 mL<58.4 mmol) is added and the mixture is heated to 50° C. for 4 h. The mixture is diluted with CHCl3 (60 mL), washed with 5percent HCl (2*40 mL), dried over MgSO4 and concentrated to a brown oily-solid (8.31 g). The crude material is chromatographed over a standard 90 g Biotage column, eluding with 10percent EtOAc/hexane (1 L) followed by 15percent EtOAc/hexane (1 L). The appropriate fractions are combined and concentrated to afford 4.22 g (91percent) of methyl 3-hydroxy-4-[(trimethylsilyl)ethynyl]benzoate as a yellow solid. HRMS (FAB) calcd for C13H16O3Si+H: 249.0947, found 249.0947 (M+H)+.
  • 3
  • [ 478169-68-5 ]
  • N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-1-benzofuran-6-carboxamide [ No CAS ]
  • 4
  • [ 478169-68-5 ]
  • [ 77095-51-3 ]
  • 5
  • [ 478169-68-5 ]
  • [ 77095-51-3 ]
  • [ 501892-53-1 ]
YieldReaction ConditionsOperation in experiment
1.83 g (93%) With sodium hydroxide; copper(I) iodide; In methanol; ethanol; water; triethylamine; Methyl-3-hydroxy-4-[(trimethylsilyl)ethynyl]benzoate (3.0 g, 12.1 mmol) is dissolved in 30 ml 1:1 EtOH/Et3N, is treated with cuprous iodide (114 mg, 0.6 mmol), and the reaction is warmed to 75° C. for 3 h. The mixture is treated with DARCO and 15 ml MeOH and is heated to reflux for 1 h. The reaction is filtered through a fine fritted glass funnel, the filtrate is treated with 3N NaOH (24.2 ml, 72.5 mmol), and the mixture is stirred overnight at RT. The mixture is concentrated to dryness, the residue is dissolved in 20 ml water, and the pH of the mixture is adjusted to 2 with 12N HCl. The resulting yellow precipitate is collected, washed with water, and is dried to give 1.83 g (93percent) of benzofuran-6-carboxylic acid as a tan solid. HRMS (FAB) calcd for C9H6O3+H: 163.0395, found 163.0389 (M+H)+.
  • 6
  • [ 478169-68-5 ]
  • [ 478169-69-6 ]
YieldReaction ConditionsOperation in experiment
350 mg (83%) With formic acid; Methyl 3-hydroxy-4-[(trimethylsilyl)ethynyl]benzoate (540 mg, 2.17 mmole) is combined with 4 ml formic acid under nitrogen. The reaction is warmed to 80° C. for 12 h, is cooled to rt, and the volatiles are removed in vacuo. The black residue is chromatographed over 25 g silica gel (230-400 mesh) eluding with 15percent EtOAc/hexane. The appropriate fractions are combined and concentrated to provide 350 mg (83percent) of methyl 4-acetyl-3-hydroxybenzoate as a pale yellow solid. 1H NMR (CDCl3) delta 2.70, 3.95, 7.54, 7.64, 7.82, 12.10 ppm.
  • 7
  • [ 478169-68-5 ]
  • [ 67-56-1 ]
  • [ 77095-51-3 ]
YieldReaction ConditionsOperation in experiment
93% Methyl 3-hydroxy-4-[(trimethylsilyl)ethynyl]benzoate (3.0 g, 12.1 mmol) is dissolved in 1:1 EtOH/Et3N (30mL), is treated with CuI (114 mg, 0.6 mmol), and the reaction is warmed to 75° C. for 3 h. The mixture is treated with DARCO and MeOH (15 mL) and heated to reflux for 1 h. The reaction is filtered through a fine fritted-glass funnel, the filtrate is treated with 3N NaOH (24.2 ml, 72.5 mmol), and the mixture is stirred overnight at RT. The mixture is concentrated to dryness, the residue is dissolved in H2O (20 mL), and the pH of the mixture is adjusted to 2 with 12N HCl. The resulting yellow precipitate is collected, washed with water, and is dried to give 1.83 g (93percent) of benzofuran-6-carboxylic acid as a tan solid. HRMS (FAB) calcd for C9H6O3+H: 163.0395, found 163.0389 (M+H)+.
  • 8
  • [ 478169-68-5 ]
  • [ 67-56-1 ]
  • [ 588703-29-1 ]
YieldReaction ConditionsOperation in experiment
70% Methyl 3-hydroxy-4-[(trimethylsilyl)ethynyl]benzoate (4.15 g, 16.7 mmol) is dissolved in MeOH (45 ml) and treated with DIA (2.34 ml, 16.7 mmol). Copper iodide (159 mg, 0.84 mmol) is added portion-wise and the reaction is heated at 75° C. for 3 h. DARCO (2 g) is added and the reaction is stirred at 95° C. for an additional 2 h, then overnight at RT. The reaction is filtered, concentrated to a brown oil and the crude material is chromatographed over 300 g slurry-packed silica gel, eluting with 10percent EtOAc/hexane. The appropriate fractions are collected and concentrated to afford 2.05 g (70percent) of methyl 1-benzofuran-6-carboxylate as an orange crystalline solid. 1H NMR (400 MHz, CDCl3) delta3.97, 6.84, 7.65, 7.78, 7.98, 8.22 ppm.
 

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