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Chemical Structure| 10602-00-3 Chemical Structure| 10602-00-3

Structure of 4-Ethynylbenzoic acid
CAS No.: 10602-00-3

Chemical Structure| 10602-00-3

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Product Details of [ 10602-00-3 ]

CAS No. :10602-00-3
Formula : C9H6O2
M.W : 146.14
SMILES Code : C(#C)C1=CC=C(C(=O)O)C=C1
MDL No. :MFCD00168819
InChI Key :SJXHLZCPDZPBPW-UHFFFAOYSA-N
Pubchem ID :589706

Safety of [ 10602-00-3 ]

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

Computational Chemistry of [ 10602-00-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 41.34
TPSA ?

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

37.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.63
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

2.15
Log Po/w (WLOGP)?

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

1.45
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.

2.16
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

1.84
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.85

Water Solubility

Log S (ESOL):?

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

-2.44
Solubility 0.533 mg/ml ; 0.00365 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.

-2.57
Solubility 0.397 mg/ml ; 0.00272 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

-1.83
Solubility 2.15 mg/ml ; 0.0147 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.

-5.66 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

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)

1.48

Application In Synthesis of [ 10602-00-3 ]

* 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 [ 10602-00-3 ]

[ 10602-00-3 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 111291-97-5 ]
  • [ 10602-00-3 ]
  • 2
  • [ 619-58-9 ]
  • [ 10602-00-3 ]
  • [ 16819-43-5 ]
  • [ 116075-75-3 ]
  • 3
  • [ 925692-74-6 ]
  • [ 10602-00-3 ]
  • [ 124480-95-1 ]
  • 3-[4-(3,5-diethoxybenzoyloxy)phenyl]-5-(4-cyanophenyl)-isoxazole [ No CAS ]
  • 4
  • [ 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.
  • 5
  • [ 10602-00-3 ]
  • [ 4181-20-8 ]
  • [ 1558965-63-1 ]
YieldReaction ConditionsOperation in experiment
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In tetrahydrofuran; at 20℃; for 20h;Inert atmosphere; Following a literature procedure [10] with slight modification, amixture of 2 (167 mg, 0.268 mmol) and 1 [9] (33 mg, 0.22 mmol) inTHF (7 mL) was stirred under nitrogen atmosphere until a homogeneoussolution was obtained. After that bis(triphenylphosphine)palladium(II) dichloride (2 mg, 0.003 mmol) and copper(I) iodide(2 mg, 0.01 mmol) were added and the reaction mixturewas stirredunder nitrogen atmosphere at room temperature. After 20 h, thereaction mixturewas redissolved in CH2Cl2 andwashed withwater.The organic phase was combined and dried over anhydrous MgSO4.After the removal of solvent under reduced pressure, the crudeproduct was precipitated in MeOH/CH2Cl2 to obtain 3 as a brownsolid (69 mg, 48percent). 1H NMR (DMSO-d6) d 6.78e6.94 (m, 6H), 7.24e7.46 (m, 4 H), 7.56e7.74 (m, 6H); MALDI-TOF-MS m/z obsd 388.508[(M 2I)] calcd avg mass 641.238 (M C27H17I2NO2). Due tothe change in colour observed during storage, compound 3 wasdirectly used in the next step without further purification andcharacterization.
  • 6
  • [ 1000623-95-9 ]
  • [ 10602-00-3 ]
  • [ 205877-26-5 ]
  • C59H57N3O4S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
15% A mixture of DPP-Br2 (100mg, 0.146mmoles), Ethynyl benzoic acid (20.3mg, 0.138mmoles) and N-(4-ethynylphenyl)-N-phenylbenzenamine (35.6mg, 0.138mmoles) in dry THF (15mL) and NEt3 (3mL) was degassed with dinitrogen for 20min, Then Pd2(dba)3 (80.10mg, 0.087mmol) and AsPh3 (178mg, 0.584mmole) were added to the mixture. The solution was refluxed for 12h under dinitrogen. The solvent was removed in vacuum. The residue was purified on a column chromatograph (silica gel) using CHCl3 /methanol=95/05as eluent to afford DPP1 Yield: 15.0%. 1H NMR (400MHz, CD2Cl2) delta 8.53-8.52 (d, J=7.2Hz, 2H), 7.24-7.23 (d, J=2.1Hz, 4H), 7.22 (t, J=2.3Hz, 4H), 7.20 (d, J=1.4Hz, 2H), 7.18 (d, J=4.0Hz 2H), 7.01 (d, J=2.0Hz, 4H), 7.00 (d, J=6.3, 4H), 3.84 (t, J=7.5Hz, 4H), 1.26-1.14 (m, 16H), 0.82-0.76 (m, 14H). MALDI-TOF MS Calcd. for936.2; Found 937.51. HRMS C59H57N3O4S2 calcd. for 936.03889 found 936.3823. Anal. Calcd. For C59H57N3O4S2% (936.23): C, 75.69; H, 6.14; N, 4.49. Found: C, 75.65; H, 6.13; N, 4.50.
  • 7
  • [ 1000623-95-9 ]
  • [ 10602-00-3 ]
  • C48H48N2O6S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% A mixture of DPP-Br2 (100mg, 0.146mmol), Ethynyl benzoic acid (135mg, 0.96mmol), in dry THF (15mL) and NEt3 (3mL) was degassed with dinitrogen for 10min. Then Pd2(dba)3 (83mg, 0.09mmol) and AsPh3 (190mg, 0.60mmol) were added to the mixture. The solution was refluxed for 12h under dinitrogen. The solvent was removed in vacuum. The residue was purified on a column chromatograph (silica gel) using CHCl3/methanol=85/15 as eluent to afford DPP2 Yield: 65.0%. 1H NMR (500MHz, CDCl3+CD3OD) delta 8.64 (d, J=4.2Hz, 2H), delta 7.93-7.92 (d, J=8.4Hz, 4H), 7.86 (d, J=8.3Hz, 4H) 7.23 (d, J=4.2Hz, 2H), 3.95-3.90 (t, 4H), 1.41-1.18 (m, 16H), 0.93-0.79 (m, 14H). MALDI-TOF MS Calcd. for 813.0; Found 814.12. HRMS C48H48N2O6S2 calcd for 816.06766 found 813.06778. Anal. Calcd. For C48H48N2O6S2% (813.03): C, 70.09; H, 5.95; N, 3.45. Found: C, 70.11; H, 5.93; N, 3.42.
 

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