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Chemical Structure| 873-73-4 Chemical Structure| 873-73-4

Structure of 873-73-4

Chemical Structure| 873-73-4

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Product Citations

Product Citations

Krzysztof Kuciński ; Grzegorz Hreczycho ;

Abstract: Commercially available and inexpensive potassium bis(trimethylsilyl)amide (KHMDS) serves as an efficient transition metal-free catalyst for the catalytic sp C−H silylation of several terminal alkynes including two pharmaceuticals. Overall, the presented system allows the synthesis of various attractive silylacetylenes under mild conditions, making this approach an environmentally benign and sustainable alternative to existing synthetic solutions.

Alternative Products

Product Details of [ 873-73-4 ]

CAS No. :873-73-4
Formula : C8H5Cl
M.W : 136.58
SMILES Code : C#CC1=CC=C(Cl)C=C1
MDL No. :MFCD00191917
InChI Key :LFZJRTMTKGYJRS-UHFFFAOYSA-N
Pubchem ID :70118

Safety of [ 873-73-4 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H228-H315-H319-H335
Precautionary Statements:P210-P240-P241-P261-P264-P271-P280-P302+P352-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P370+P378-P403+P233-P405-P501
Class:4.1
UN#:1325
Packing Group:

Computational Chemistry of [ 873-73-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 39.39
TPSA ?

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

0.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.3
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

3.21
Log Po/w (WLOGP)?

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

2.4
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.

3.44
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

3.11
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.89

Water Solubility

Log S (ESOL):?

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

-3.2
Solubility 0.0857 mg/ml ; 0.000627 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.

-2.88
Solubility 0.179 mg/ml ; 0.00131 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

-3.06
Solubility 0.118 mg/ml ; 0.000861 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

Low
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.

-4.85 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

2.0
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)

1.66

Application In Synthesis of [ 873-73-4 ]

* 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 [ 873-73-4 ]

[ 873-73-4 ] Synthesis Path-Downstream   1~13

  • 1
  • [ 873-73-4 ]
  • [ 4016-63-1 ]
  • 2-Amino-8-(4-chloro-phenylethynyl)-9-((2R,3R,4S,5R)-3,4-dihydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-1,9-dihydro-purin-6-one [ No CAS ]
  • 2
  • [ 873-73-4 ]
  • [ 7681-65-4 ]
  • [ 63558-65-6 ]
  • [ 393857-01-7 ]
YieldReaction ConditionsOperation in experiment
With triethylamine;dichlorobis(triphenylphosphine)palladium[II]; In dichloromethane; EXAMPLE 3 Preparation of 4-chloro-5-(4-chlorophenylethynyl)pyrimidine A mixture of 0.6 g of 1-chloro-4-ethynylbenzene, 1.44 g of <strong>[63558-65-6]4-chloro-5-iodopyrimidine</strong> (J. Chem. Soc. Perkins Trans. I, 1977,621, Allen et al), 7.0 cc of triethylamine, 58 mg of copper iodide and 108 mg of dichlorobis(triphenylphosphine)palladium II was stirred at room temperature under nitrogen for 18 hours. The reaction mixture was evaporated in vacuo. The resulting tan solid was partitioned between water and dichloromethane and the organic extracts washed twice with water, dried over sodium sulfate and evaporated to give a dark brown solid, 1.57 g. The solid was redissolved in dichloromethane and hexanes added to give 120 mg of a beige powder after filtration. The filtrate was purified by column chromatography on silica gel using 1:1 ethyl acetate/dichloromethane as the eluant. The middle rf spot fractions (silica gel TLC in 1:1) were pooled and evaporated to give 0.8 g of a yellow solid, 4-chloro-5-(4-chlorophenylethynyl)-pyrimidine
  • 3
  • [ 873-73-4 ]
  • [ 263351-43-5 ]
  • C20H20ClNO2 [ No CAS ]
  • 6
  • [ 873-73-4 ]
  • [ 154237-70-4 ]
  • 4-(4-chlorophenylethynyl)-3-cyanopyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
59% General procedure: 4-Bromo-3-cyanopyridine 27 (92 mg, 0.5 mmol) in THF (5 mL)was added to CuI (9.6 mg, 50 lmol), (Ph3P)4Pd (29 mg, 25 lmol)and Na ascorbate (9.9 mg, 50 lmol) in Et3N (5 mL) under Ar. Themixture was stirred at 40 C for 30 min. Phenylethyne 21a(76.5 mg, 0.75 mmol) was added and the mixture was stirred at40 C for 10 h. Evaporation and chromatography (petroleumether/EtOAc 3:1) gave 28a (80 mg, 78%) as an off-white powder.
  • 7
  • [ 873-73-4 ]
  • [ 74-96-4 ]
  • [ 124-38-9 ]
  • [ 20026-96-4 ]
  • 8
  • [ 873-73-4 ]
  • [ 108-95-2 ]
  • [ 42019-78-3 ]
  • 10
  • [ 873-73-4 ]
  • [ 19591-17-4 ]
  • N-(2-((4-chlorophenyl)ethynyl)phenyl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
> 99% With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; triphenylphosphine; In acetonitrile; at 20℃;Inert atmosphere; <strong>[19591-17-4]N-(2-iodophenyl)acetamide</strong> (100.0 mg, 0.38 mmol, 1.0 equiv) in CH3CN (5.0 mL) was added sequentially with PdCl2(PPh3)2 (5.4 mg, 0.01 mmol, 0.02 equiv), Ph3P (4.0 mg, 0.02 mmol, 0.04equiv), 1-chloro-4-ethynylbenzene (57.6 mg, 0.42 mmol, 1.1 equiv). The resulting solution was degassed by passing through a steady stream of argon for 30 min (flask 1). In the meantime in another flask, a mixture of CuI (3.0 mg, 0.02 mmol, 0.04 equiv) in Et3N was also degassed bypassing through a steady stream of argon for 30 min (flask 2). After degassing, the mixture ofCuI in Et3N in flask 2 was transferred into the solution in flask 1 using a syringe with wide-boarneedle which resulted in the reaction solution turning yellow and giving white precipitates. The reaction mixture was allowed to stir at room temperature overnight and was quenched byaddition with sat. aq. NH4Cl. The separated aqueous phase was extracted with EtOAc (3x times).The combined organic phases were washed with sat. aq. NaCl, dried over anh. Na2SO4 and concentrated under reduced pressure. The crude material was purified by SiO2 column chromatography eluting with 30-50% EtOAc-hexane to yield 114.6 mg of compound 1d (>99%)as a white solid.
  • 11
  • [ 873-73-4 ]
  • [ 34883-46-0 ]
  • 1-((4-chlorophenyl)ethynyl)-2-phenoxybenzene [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; for 10h;Inert atmosphere; (1)To <strong>[34883-46-0]1-iodo-2-phenoxybenzene</strong> (2g, 6.8mmol)a solution of triethylamine (20 mL) added to 4-chlorophenylacetylene(1.1g, 8.1mmol),Pd(PPh3)2Cl2 (95 mg, 135 mumol), CuI (26 mg, 135 mumol).Under argon protection conditions,After the reaction was carried out for 10 hours,Triethylamine was removed under reduced pressure.The residue was extracted with ethyl acetate (20 mL×3).Then use water (10mL)Wash twice with saturated brine (10 mL) and dry over anhydrous sodium sulfate.Filter and remove the solvent under pressure.The residue was purified by silica gel column chromatography eluting elut1-((4-Chlorophenyl)ethynyl)-2-phenoxybenzene(1.9 g, 92% yield).
  • 12
  • [ 873-73-4 ]
  • [ 6638-05-7 ]
  • C17H16ClN3O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% With potassium fluoride; sodium azide; silver carbonate; In N,N-dimethyl-formamide; at 50℃; for 6.0h; General procedure: to a solution of phenylacetylene (1a)(0.055 mL, 0.5 mmol), 2,6-di-tert-butyl-4-methylphenol(BHT) (2a) (133 mg, 0.6 mmol), NaN3 (39 mg, 0.6 mmol)and KF (58 mg, 1.0 mmol) in DMF (1 mL) at 50 C, Ag2CO3(41 mg, 0.15 mmol) was added. The reaction mixture wasthen stirred for 6 h when TLC conformed that substrate 1a was consumed. The resulting reaction mixture was cooled toroom temperature and extracted by dichloromethane(3×15 mL). The organic layer was washed with brine(3×40 mL), dried over MgSO4 and concentrated. Purificationof the crude product via flash column chromatography (silicagel; petroleum ether) and concentratinon in vacuo affordedthe desired product of 3a-N2/3a-N1 in 91% yield.
  • 13
  • [ 873-73-4 ]
  • [ 106-51-4 ]
  • [ 42019-78-3 ]
 

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