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Chemical Structure| 932710-63-9 Chemical Structure| 932710-63-9

Structure of Amphos
CAS No.: 932710-63-9

Chemical Structure| 932710-63-9

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Product Details of [ 932710-63-9 ]

CAS No. :932710-63-9
Formula : C16H28NP
M.W : 265.37
SMILES Code : CN(C)C1=CC=C(P(C(C)(C)C)C(C)(C)C)C=C1
MDL No. :MFCD09265102
InChI Key :IQTHEAQKKVAXGV-UHFFFAOYSA-N
Pubchem ID :11714598

Safety of [ 932710-63-9 ]

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

Computational Chemistry of [ 932710-63-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 18
Num. arom. heavy atoms 6
Fraction Csp3 0.62
Num. rotatable bonds 4
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 87.85
TPSA ?

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

16.83 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.57
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

3.58
Log Po/w (WLOGP)?

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

4.46
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.

4.37
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

4.39
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

4.07

Water Solubility

Log S (ESOL):?

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

-3.72
Solubility 0.0502 mg/ml ; 0.000189 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.

-3.62
Solubility 0.0637 mg/ml ; 0.00024 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

-5.04
Solubility 0.00241 mg/ml ; 0.0000091 mol/l
Class?

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

Moderately 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

Yes
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.

-5.38 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

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)

3.47

Application In Synthesis of [ 932710-63-9 ]

* 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.

  • Upstream synthesis route of [ 932710-63-9 ]

[ 932710-63-9 ] Synthesis Path-Upstream   1~8

  • 1
  • [ 121-69-7 ]
  • [ 932710-63-9 ]
YieldReaction ConditionsOperation in experiment
96% With dmap; copper (I) acetate In toluene at 120℃; for 8 h; Inert atmosphere Under argon protection,To the drying reactor was added 1 L of toluene,Followed by the addition of N, N-dimethylaniline (121 g, 1 mol)4-dimethylaminopyridine (122 g, 1 mol),Cuprous acetate (1.2 g, 0.01 mmol)And di-tert-butylphosphonium chloride (181 g, 1 mol)And then heated to 120 C for 8 hours.After completion of the reaction, 1 L of water was added to the quenching reaction,Then extracted,The organic layer was dried over anhydrous magnesium sulfate,filter,After distillation under reduced pressure to give a yellow solid,This was lyophilized in 1 L of n-hexane to recrystallize to give a white solid [4- (N, N-dimethylamino) phenyl] di-tert-butylphosphine 254 g,Yield 96percent.
References: [1] Patent: CN106349286, 2017, A, . Location in patent: Paragraph 0009; 0010.
  • 2
  • [ 13716-10-4 ]
  • [ 108949-55-9 ]
  • [ 932710-63-9 ]
YieldReaction ConditionsOperation in experiment
85%
Stage #1: at -30℃; for 0.166667 h; Inert atmosphere
Stage #2: With ammonium chloride In water at -30℃; for 0.5 h;
The reaction system is cooled to -30 ° C, under the protection of nitrogen flow,Adding catalyst to remove water by vacuum dryingAfter the powder was 10.2 g, the reaction was stirred for 10 min.Further, 930 g of di-tert-butylphosphonium chloride was added dropwise.The dropping process controls the reaction temperature below -30 ° C, and the dropwise addition is completed, and the temperature is raised to 50 ° C for 3 hours to obtain di-tert-butyl-4-dimethylaminophenylphosphine. The reaction system was again cooled to -30 ° C, and 1.5 L of a saturated aqueous solution of ammonium chloride was added dropwise with stirring.After stirring for 0.5 h, the mixture was allowed to stand for stratification under the protection of a nitrogen stream.The liquid is separated, and the upper organic phase is concentrated and concentrated to obtain a yellow viscous material for high vacuum distillation under reduced pressure.The degree of vacuum is 0.3-0.5 mmHg, and the fraction of 120 ° C - 140 ° C is collected, and after cooling, it is an off-white solid.That is, the ligand di-tert-butyl-4-dimethylaminophenylphosphine has a yield of 1145-1160 g, a purity of not less than 97percent, and a yield of 81.5percent to 85.0percent.
References: [1] Patent: CN108659054, 2018, A, . Location in patent: Paragraph 0057; 0059; 0060.
  • 3
  • [ 13716-10-4 ]
  • [ 7353-91-5 ]
  • [ 932710-63-9 ]
YieldReaction ConditionsOperation in experiment
85%
Stage #1: at -60℃; for 0.133333 h; Inert atmosphere
Stage #2: With ammonium chloride In water at -60℃; for 0.5 h;
The reaction system is cooled to -60 ° C under the protection of nitrogen flow.Adding catalyst to the vacuum drying to remove water, copper bromideAfter the powder was 14.8 g, the reaction was stirred for 8 min, and 930 g of di-tert-butylphosphonium chloride was added dropwise.The dropping process controls the reaction temperature below -60 ° C, and the dropwise addition is completed, and the temperature is raised to 55 ° C for 4 hours to obtain di-tert-butyl-4-dimethylaminophenylphosphine. The reaction system was again cooled to below -60 ° C, and 1.5 L of a saturated aqueous solution of ammonium chloride was added dropwise with stirring, and the mixture was stirred for 0.5 h.After standing and layering,The liquid is separated under the protection of a nitrogen stream, and the upper organic phase is concentrated and concentrated to obtain a yellow viscous material for high vacuum distillation under reduced pressure.The degree of vacuum is 0.3-0.5 mmHg, and the fraction of 120 ° C - 140 ° C is collected, and after cooling, it is an off-white solid.It is a ligand of di-tert-butyl-4-dimethylaminophenylphosphine, and the yield is 1145-1160 g, the purity is not less than 97percent, and the yield is 81.5percent to 85.0percent.
References: [1] Patent: CN108659054, 2018, A, . Location in patent: Paragraph 0062; 0064; 0065.
  • 4
  • [ 819-19-2 ]
  • [ 586-77-6 ]
  • [ 932710-63-9 ]
YieldReaction ConditionsOperation in experiment
49.2 g
Stage #1: With n-butyllithium In hexane; toluene at 50℃; for 12 h; Inert atmosphere
Stage #2: at 5℃; for 12 h; Inert atmosphere
The reaction flask was replaced with a nitrogen atmosphere, and 32 g of di-tert-butylphosphine and 200 mL of toluene were added to 1 L of the reaction flask,Start the magnetic stirrer, add 0.1M 2.5M n-butyllithium at -10 ° C, drip to 50 ° C for 12 hours, drop the temperature of the reaction solution to -10 ° C,A solution of 40 g of N, N-dimethyl-p-bromoaniline in toluene was added dropwise to the reaction at 50 ° C for 12 hours, after which the reaction solution was lowered to room temperature,10 mL of triethylamine aqueous solution was added dropwise under ice-cooling, and the upper organic phase was depiltrated under nitrogen protection,Distillation under reduced pressure, collecting 120 ° C (15 mm Hg) di-tert-butyl-4-dimethylaminophenylphosphine 49.2 g
References: [1] Patent: CN105237568, 2017, B, . Location in patent: Paragraph 0061-0063.
  • 5
  • [ 13716-10-4 ]
  • [ 932710-63-9 ]
References: [1] Patent: CN108659054, 2018, A, . Location in patent: Paragraph 0067; 0069; 0070.
  • 6
  • [ 698-69-1 ]
  • [ 932710-63-9 ]
References: [1] Patent: CN108659054, 2018, A, .
  • 7
  • [ 586-77-6 ]
  • [ 932710-63-9 ]
References: [1] Patent: CN108659054, 2018, A, .
  • 8
  • [ 698-70-4 ]
  • [ 932710-63-9 ]
References: [1] Patent: CN108659054, 2018, A, .
 

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