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Chemical Structure| 111291-97-5 Chemical Structure| 111291-97-5

Structure of 111291-97-5

Chemical Structure| 111291-97-5

tert-Butyl 4-ethynylbenzoate

CAS No.: 111291-97-5

4.5 *For Research Use Only !

Cat. No.: A280588 Purity: 97%

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Product Details of [ 111291-97-5 ]

CAS No. :111291-97-5
Formula : C13H14O2
M.W : 202.25
SMILES Code : O=C(OC(C)(C)C)C1=CC=C(C#C)C=C1
MDL No. :MFCD09037869
InChI Key :FWAUARVBLKIMRS-UHFFFAOYSA-N
Pubchem ID :13965008

Safety of [ 111291-97-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 111291-97-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 6
Fraction Csp3 0.31
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 60.12
TPSA ?

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

26.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.04
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

3.01
Log Po/w (WLOGP)?

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

2.7
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.

3.31
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

3.15
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.04

Water Solubility

Log S (ESOL):?

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

-3.09
Solubility 0.165 mg/ml ; 0.000816 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.

-3.23
Solubility 0.12 mg/ml ; 0.000593 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

-3.38
Solubility 0.0833 mg/ml ; 0.000412 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.

-5.4 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<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)

2.02

Application In Synthesis of [ 111291-97-5 ]

* 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 [ 111291-97-5 ]

[ 111291-97-5 ] Synthesis Path-Downstream   1~30

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  • [ 108473-08-1 ]
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  • [ 288387-66-6 ]
  • [ 1026325-20-1 ]
  • 9
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  • [ 476168-52-2 ]
  • C46H58O12 [ No CAS ]
  • 10
  • [ 865-47-4 ]
  • [ 62480-31-3 ]
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  • 11
  • [ 540-38-5 ]
  • [ 111291-97-5 ]
  • 4-(4'-hydroxyphenylethynyl)benzoic acid tert-butyl ester [ No CAS ]
  • 13
  • [ 111291-97-5 ]
  • 1,3-bis[4'-(4''-hydroxyphenylethynyl)benzoylaminomethyl]benzene [ No CAS ]
  • 14
  • [ 111291-97-5 ]
  • methyl-phosphonic acid mono-(4-{4-[3-({4-[4-(hydroxy-methyl-phosphinoyloxy)-phenylethynyl]-benzoylamino}-methyl)-benzylcarbamoyl]-phenylethynyl}-phenyl) ester [ No CAS ]
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  • [ 111291-97-5 ]
  • [ 111323-82-1 ]
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  • 18
  • [ 111291-97-5 ]
  • 4-{2-[2-(2,2-Dimethyl-propionylamino)-4-hydroxy-7,8-dihydro-pteridin-6-yl]-ethyl}-benzoic acid tert-butyl ester [ No CAS ]
  • 19
  • [ 586-75-4 ]
  • pinoresinol [ No CAS ]
  • [ 111291-97-5 ]
  • 22
  • [ 111291-97-5 ]
  • [ 116387-38-3 ]
  • 23
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  • [ 116387-23-6 ]
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  • [ 116387-33-8 ]
  • 27
  • [ 586-75-4 ]
  • [ 111291-97-5 ]
  • 28
  • copper (III) iodide [ No CAS ]
  • 3-bromo-4-(2-phenylethenyl)pyridine [ No CAS ]
  • bistriphenyl phosphinepalladium dichloride [ No CAS ]
  • [ 111291-97-5 ]
  • tert-butyl 4-[2-(4-(2-phenylethenyl)-pyridin-3-yl)ethynyl]benzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
33% With triethylamine; In N,N-dimethyl-formamide; 3-Bromo-4-(2-phenylethenyl)pyridine (0.74 g, 2.9 mmol) was dissolved in DMF (1.4 ml). The solution was treated with <strong>[111291-97-5]ter<strong>[111291-97-5]t-butyl 4-ethynylbenzoate</strong></strong> (0.93 g 4.6 mmol), copper (III) iodide (0.023 g, 0.21mmol) and triethylamine (0.64 g, 6.3 mmol). The reaction mixture was degassed by bubbling through argon and the catalyst, bistriphenyl phosphinepalladium dichloride (0.03 g, 0.043 mmol), was added. The reaction was heated to 90-100 C. for 3 hours and then partitioned between ethyl acetate and water. The organic layer was washed with water (3*), dried (MgSO4) and evaporated. The residue was purified by chromatography (eluding with ethylacetate/hexane) to give tert-butyl 4-[2-(4-(2-phenylethenyl)-3-pyridyl)ethynyl]benzoate as a dark oil (0.36 g, 33%). MS ?CI+!: 382 [M+H]+
  • 29
  • 6-bromo-2-pivaloylamino-4-hydroxypyrido[2,3-d]pyrimidine [ No CAS ]
  • [ 111291-97-5 ]
  • 2-pivaloylamino-4-hydroxy-6-(4-tert.-butoxycarbonylphenylethynyl)pyrido[2,3-d]pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
1.91 g (69%) With copper(I) iodide; triethylamine; triphenylphosphine;palladium(II) chloride; In acetonitrile; EXAMPLE 12 2-Pivaloylamino-4-hydroxy-6-(4-tert.-butoxycarbonylphenylethynyl)pyrido[2,3-d]pyrimidine A mixture of 2.0 g of 2-pivaloylamino-4-hydroxy-6-bromopyrido[2,3-d]pyrimidine (prepared according to Example 6), 1.31 g of <strong>[111291-97-5]tert.-butyl 4-ethynylbenzoate</strong>, 2.57 ml of triethylamine, 0.11 g of palladium chloride, 0.32 g of triphenylphosphine, and 0.05 g of cuprous iodide in 150 ml of acetonitrile is heated at reflux under nitrogen for 2.5 hours. The reaction mixture is cooled to room temperature and then in an ice bath. The solid is collected and washed with small portions of cold acetonitrile to yield 1.91 g (69%) of 2-pivaloylamino-4-hydroxy-6-(4-tert.-butoxycarbonylphenylethynyl)pyrido[2,3-d]pyrimidine as a pale yellowish powder, which is sufficiently pure for the next reaction.
  • 30
  • [ 16450-41-2 ]
  • [ 10602-00-3 ]
  • [ 111291-97-5 ]
  • [ 51766-21-3 ]
  • [ 116387-23-6 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In tetrahydrofuran; methanol; dichloromethane; EXAMPLE 7 Diethyl N-(4-ethynylbenzoyl)-L-glutamate To a solution of 0.55 g of 4-ethynylbenzoic acid (obtained from <strong>[111291-97-5]tert.-butyl 4-ethynylbenzoate</strong> in 84% yield by hydrolysis with trifluoroacetic acid) in 50 ml of anhydrous ether and 25 ml of anhydrous tetrahydrofuran is added 1.58 ml of triethylamine. This is followed by 1.00 g of phenyl N-phenylphosphoramidochloridate. After stirring the reaction mixture at room temperature under nitrogen for 0.5 hour, 0.90 g of diethyl L-glutamate is added in one portion. The mixture is allowed to stir for another 8 hrs. After a workup, the residue is subjected to column chromatography using a 1% methanol:methylene chloride mixture as the eluent. The major fraction isolated from the column contained 0.68 g (54%) of diethyl N-(ethynylbenzoyl)-L-glutamate as an oil which slowly solidified: NMR (CDCl3, 300 MHz) delta 1.25 (t, 3H, J=6.9 Hz), 1.33 (t, 3H, J=6.9 Hz), 2.11-2.60 (m, 4H), 3.23 (s, 1H), 4.09 (q, 2H, J=6.9 Hz), 4.27 (1, 2H, J=6.9 Hz), 4.80 (m, 1H), 7.12 (d, 1H, J=7.2 Hz), 7.59 (d, 2H, J=8.4 Hz), 7.81 (d, 2H, J=8.4 Hz); IR (KBr) 3330, 3280, 2990, 1735, 1640, 1520, 1380, 1200, 1105, 1020, 855, and 770 cm -1.
 

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