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Chemical Structure| 564483-19-8 Chemical Structure| 564483-19-8

Structure of t-BuXPhos
CAS No.: 564483-19-8

Chemical Structure| 564483-19-8

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Product Citations

Product Citations

Chen, Zhi-Hao ; Daugulis, Olafs ; Brookhart, Maurice ;

Abstract: A well-defined Pd complex [(tBuXPhos)Pd(Me)(BArf)] bearing a bulky monophosphine ligand was synthesized and fully characterized. X-ray diffraction anal. shows that the 1,3,5-triisopropylaryl group of the dialkylbiaryl phosphine ligand exhibits a weak η6-interaction with the Pd(II) center. This catalyst exhibits excellent functional group tolerance and polymerizes propargyl esters containing benzoyl and acetyl groups, propargyl Me ether, propargyl alc., benzyl acetylene, and Ph acetylene to yield polymers with Mn values at 5-15 kDa with monomodal mol. weight distributions between ∼1.4 and 2.1.

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Product Details of [ 564483-19-8 ]

CAS No. :564483-19-8
Formula : C29H45P
M.W : 424.64
SMILES Code : CC(C1=C(C2=CC=CC=C2P(C(C)(C)C)C(C)(C)C)C(C(C)C)=CC(C(C)C)=C1)C
MDL No. :MFCD06411306
InChI Key :SACNIGZYDTUHKB-UHFFFAOYSA-N
Pubchem ID :11618717

Safety of [ 564483-19-8 ]

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

Computational Chemistry of [ 564483-19-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 30
Num. arom. heavy atoms 12
Fraction Csp3 0.59
Num. rotatable bonds 7
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 142.82
TPSA ?

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

13.59 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

5.02
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

8.47
Log Po/w (WLOGP)?

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

9.43
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.

7.73
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

10.04
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

8.14

Water Solubility

Log S (ESOL):?

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

-7.64
Solubility 0.00000966 mg/ml ; 0.0000000228 mol/l
Class?

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

Poorly soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-8.63
Solubility 0.000001 mg/ml ; 0.0000000024 mol/l
Class?

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

Poorly 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

-9.81
Solubility 0.0000000653 mg/ml ; 0.0000000002 mol/l
Class?

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

Poorly 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

No
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

Yes
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.

-2.88 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

1.0
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

1.0
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<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)

4.8

Application In Synthesis of [ 564483-19-8 ]

* 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 [ 564483-19-8 ]

[ 564483-19-8 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 890315-75-0 ]
  • [ 367-27-1 ]
  • [ 131274-22-1 ]
  • [ 564483-19-8 ]
  • [ 890316-65-1 ]
YieldReaction ConditionsOperation in experiment
With citric acid;tris-(dibenzylideneacetone)dipalladium(0); palladium diacetate; In ethyl acetate; toluene; Example 557 0.018 mL of 2,4-difluorophenol was added to 1 mL of toluene suspension containing 10 mg of 60percent sodium hydride at room temperature, and the resulting mixture was heated to reflux under nitrogen atmosphere for 15 minutes. After the reaction mixture was cooled to room temperature, 0.5 mL of toluene solution containing 4.7 mg of 2-(di-tert-butylphosphino)-2',4',6'-triisopropylbiphenyl, 1.7 mg of palladium acetate and 70 mg of tert-butyl 2-(benzamido)-4-bromobenzoate was added and the resulting mixture was heated to reflux under nitrogen atmosphere for 4 hours. After the reaction mixture was cooled to room temperature, 4.5 mg of 60percent sodium hydride, 4.7 mg of 2-(di-tert-butylphosphino)-2',4',6'-triisopropylbiphenyl and 1.7 mg of palladium acetate were added and the resulting mixture was heated to reflux under nitrogen atmosphere for 2 hours. After the reaction mixture was cooled to room temperature, 0.018 mL of 2,4-difluorophenol, 7.4 mg of 60percent sodium hydride, 4.7 mg of 2-(di-tert-butylphosphino)-2',4',6'-triisopropylbiphenyl and 1.7 mg of palladium acetate were added and the resulting mixture was heated to reflux under nitrogen atmosphere for 2 hours. After the reaction mixture was cooled to room temperature, 1.6 mg of tri-tert-butylphosphine tetrafluoroborate and 5.1 mg of tris(dibenzylideneacetone)dipalladium(0) were added, and the resulting mixture was heated to reflux under nitrogen atmosphere for 1 hour and 30 minutes. 10percent citric acid aqueous solution and ethyl acetate were added after the reaction mixture was cooled to room temperature. The organic layer was separated and dried over anhydrous magnesium sulfate after washed with a saturated sodium chloride aqueous solution, and the solvent was evaporated under reduced pressure. The obtained residue was purified with silica gel column chromatography [Flash Tube 2008 manufactured by Trikonex Company, eluent; hexane: ethyl acetate = 4:1] to obtain tert-butyl 2-(benzamido)-4-(2,4-difluorophenoxy)benzoate.
  • 2
  • [ 100-02-7 ]
  • [ 890315-75-0 ]
  • [ 131274-22-1 ]
  • [ 564483-19-8 ]
  • [ 890315-31-8 ]
YieldReaction ConditionsOperation in experiment
With citric acid;tris-(dibenzylideneacetone)dipalladium(0); palladium diacetate; In ethyl acetate; toluene; Example 536 31 mg of 4-nitrophenol was added to 1.0 mL of toluene suspension containing of 8.9 mg of 60percent sodium hydride at room temperature, and the resulting mixture was heated to reflux under nitrogen atmosphere for 15 minutes. After the reaction mixture was cooled to room temperature, 0.5 mL of toluene solution containing 3.8 mg of 2-(di-tert-butylphosphino)-2',4',6'-triisopropylbiphenyl, 1.3 mg of palladium acetate and 56 mg of tert-butyl 2-(benzamido)-4-bromobenzoate were added and the resulting mixture was heated to reflux under nitrogen atmosphere for 3 hours. After the reaction mixture was cooled to room temperature, 1.3 mg of tri-tert-butylphosphine tetrafluoroborate and 4.1 mg of tris(dibenzylideneacetone)dipalladium(0) were added and the resulting mixture was heated to reflux under nitrogen atmosphere for 4 hours. After the reaction mixture was cooled to room temperature, 10percent citric acid aqueous solution and ethyl acetate were added and insoluble were removed by filtration. The organic layer was separated and dried over anhydrous magnesium sulfate after washed with a saturated sodium chloride aqueous solution, and the solvent was evaporated under reduced pressure. The obtained residue was purified with silica gel column chromatography [PSQ100B (spherical) manufactured by Fuji Silysia Chemical Ltd., eluent; hexane: ethyl acetate = 10:1] to obtain 18 mg of tert-butyl 2-(benzamido)-4-(4-nitrophenoxy)benzoate as white solid. 1H-NMR (CDCl3) delta: 1.65 (9H, s), 6.79 (1H, dd, J = 8.8, 2.4 Hz), 7.12-7.17 (2H, m), 7.50-7.61 (3H, m), 8.01-8.06 (2H, m), 8.09 (1H, d, J = 8.8 Hz), 8.23-8.29 (2H, m), 8.74 (1H, d, J = 2.4 Hz), 12.36 (1H, s).
  • 3
  • [ 52522-40-4 ]
  • [ 564483-19-8 ]
  • [ 1354022-32-4 ]
  • [ 1354022-31-3 ]
 

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