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Chemical Structure| 474688-76-1 Chemical Structure| 474688-76-1

Structure of 474688-76-1

Chemical Structure| 474688-76-1

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Product Details of [ 474688-76-1 ]

CAS No. :474688-76-1
Formula : C34H21Br
M.W : 509.44
SMILES Code : BrC3=CC2=C(C1=CC=CC=C1C(=C2C=C3)C5=CC4=CC=CC=C4C=C5)C7=CC6=CC=CC=C6C=C7
MDL No. :MFCD11045064
InChI Key :NNVPXSAMRFIMLP-UHFFFAOYSA-N
Pubchem ID :22247157

Safety of [ 474688-76-1 ]

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

Computational Chemistry of [ 474688-76-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 35
Num. arom. heavy atoms 34
Fraction Csp3 0.0
Num. rotatable bonds 2
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 155.04
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.

4.93
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

10.87
Log Po/w (WLOGP)?

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

10.4
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.

8.29
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

9.79
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

8.86

Water Solubility

Log S (ESOL):?

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

-10.43
Solubility 0.0000000188 mg/ml ; 0.0 mol/l
Class?

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

Insoluble
Log S (Ali)?

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

-10.83
Solubility 0.0000000075 mg/ml ; 0.0 mol/l
Class?

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

Insoluble
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

-14.8
Solubility 0.0 mg/ml ; 0.0 mol/l
Class?

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

Insoluble

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

Yes
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.

-1.69 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

2.0
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.

0.17

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)

2.84

Application In Synthesis of [ 474688-76-1 ]

* 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 [ 474688-76-1 ]

[ 474688-76-1 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 474688-76-1 ]
  • [ 867044-28-8 ]
YieldReaction ConditionsOperation in experiment
50% In an argon atmosphere, 100 mL of dehydrated THF were added to 10 g (20 mmol) of 2-bromo-9,10-di(2-naphtyl) anthracene, and the temperature of the mixture was cooled to -78 C. Then, 14 mL of n-butyllithium (in hexane, 1.6 mol/L) were dropped. After the mixture had been stirred at -78 C for 1 hour, the temperature of the mixture was increased to 0C. The temperature of the mixture was cooled to -78 C again, and 6.6 mL (60 mmol) of trimethoxyborane were added. The mixture was stirred at -78 C for 1 hour, and was then stirred at room temperature for 2 hours. 100 mL of 10-mass% hydrochloric were added, and the whole was stirred for 1 hour, followed by filtration. The resultant solid was washed with toluene to obtain 4.7 g of 9,10-diphenylanthracene-2-boronic acid (50% yield).
With hydrogenchloride; n-butyllithium; In tetrahydrofuran; hexane; (9,10-di(naphthalen-2-yl)anthracen-2-yl)boronic acid 2-bromo-9,10-di(naphthalen-2-yl)anthracene (10.00 g, 1.0 eq, 19.63 mmol) was dissolved in THF (140 mL) and cooled to -78 C. At this temperature n-BuLi (2.5M in hexane, 10.2 mL, 1.3 eq, 25.52 mmol) was added dropwise and the mixture was stirred for 2 hours. Afterwards, B(OMe)3 (6.12 g, 3.0 eq, 58.89 mmol) was added at -78 C. and the reaction mixture was allowed to warm up to room temperature. After stirring for 17 hours the mixture was quenched with HCl, the yellow precipitate was filtered off and washed with water (2*30 mL). The residue was dried in vacuo and used without further purification. Yield: 9.8 g (yield 100%)
With hydrogenchloride; n-butyllithium; (9,10-di(naphthalen-2-yl)anthracen-2-yl)boronic acid Prepared according to procedure described in EP13170862: 2-bromo-9,10-di(naphthalen-2-yl)anthracene (10.00 g, 1.0 eq, 19.63 mmol) was dissolved in THF (140 mL) and cooled to -78 C. At this temperature n-BuLi (2.5M in hexane, 10.2 mL, 1.3 eq, 25.52 mmol) was added dropwise and the mixture was stirred for 2 hours. Afterwards, B(OMe)3 (6.12 g, 3.0 eq, 58.89 mmol) was added at -78 C. and the reaction mixture was allowed to warm up to room temperature. After stiffing for 17 hours the mixture was quenched with HCl, the yellow precipitate was filtered off and washed with water (2*30 mL). The residue was dried in vacuo and used without further purification. Yield: 9.8 g (100%)
  • 2
  • [ 474688-76-1 ]
  • [ 121-43-7 ]
  • [ 867044-28-8 ]
YieldReaction ConditionsOperation in experiment
100% Prepared according to procedure described inEP13 2-bromo-9, 1 0-di(naphthalen-2-yl)anthracene (10.00 g, 1.0 eq, 19.63 mmol) was dissolved in THF (140 mE) and cooled to -78 C. At this temperature n-BuEi (2.5M in hexane, 10.2 mE, 1.3 eq, 25.52 mmol) was added dropwise and the mixture was stirred for 2 hours. Afterwards, B(OMe)3 (6.12 g, 3.0 eq, 58.89 mmol) was added at -78 C. and the reaction mixture was allowed to warm up to room temperature. After stirring for 17 hours the mixture was quenched with HC1, the yellow precipitate was filtered off and washed with water (2x30 mE). The residue was dried in vacuo and used without further purification. Yield: 9.8 g (100%)
70% Synthesis of Intermediate 1c; 5 g of Intermediate 1b (9.81 mmol) was dissolved in 70 ml of THF dried under nitrogen atmosphere, and 4.7 ml of lithium butyl (11.8 mmol) was added to the mixture at -78 C. The mixture was stirred for one hour at the same temperature, and then 2.20 ml of trimethyl borate (29.4 mmol) was added to the mixture. The temperature of the mixture was increased to room temperature, and one hour later, 2N of an aqueous hydrochloric acid solution was added to the mixture and stirred for 3 hours. The obtained solid compound was filtered while being washed with toluene to obtain 3.27 g of light-yellow Intermediate 1c (yield 70%).
70% Synthesis of Intermediate 1c; 5 g of Intermediate 1b (9.81 mmol) was dissolved in 70 ml of THF dried under nitrogen atmosphere, and 4.7 ml of lithium butyl (11.8 mmol) was added to the mixture at -78C. The mixture was stirred for one hour at the same temperature, and then 2.20ml of trimethyl borate (29.4 mmol) was added to the mixture. The temperature of the mixture was increased to room temperature, and one hour later, 2N of an aqueous hydrochloric acid solution was added to the mixture and stirred for 3 hours. The obtained solid compound was filtered while being washed with toluene to obtain 3.27 g of light-yellow Intermediate 1c (yield 70%).
70% Synthesis of Intermediate 1c; The intermediate 1b (5g, 9.81 mmol) was dissolved in 70 ml of dried THF under a nitrogen atmosphere, and butyl lithium (4.7ml, 11.8mmol) was added dropwise thereto at -78 C. The reaction mixture was stirred at -78 C for one hour, and trimethylborate (2.20ml, 29.4mmol) was added thereto. The reaction solution was heated to room temperature and incubated for one hour. Then, a 2N HCl solution was added thereto, and the resultant solution was stirred for three hours. The resultant solid compound was washed and filtered with toluene to yield intermediate 1c as a light yellow powder (3.27g, yield: 70%).
Synthesis of Intermediate 1c; 5 g (9.81 mmol) of Intermediate 1b was dissolved in 70 ml of dried THF under a nitrogen atmosphere and 4.7 ml (11.8 mmol) of butyl lithium was added thereto at -78C. The resulting product was stirred at the same temperature for 1 hour, and 2.20ml (29.4 mmol) of trimethyl borate was added thereto. The temperature of the mixture was raised to room temperature, a 2N HCl solution was added thereto after 1 hour, and the mixture was stirred for 3 hours. The resulting solid compound was filtered while washing with toluene to obtain 3.27 g of yellow Intermediate 1c (Yield: 70%).

  • 3
  • [ 474688-76-1 ]
  • [ 5419-55-6 ]
  • [ 867044-28-8 ]
YieldReaction ConditionsOperation in experiment
84% 3-2) Synthesis of 2-bromo-9,10-di(2-naphthyl)anthracene 190 g (0.37 mol) of 2-bromo-9,10-di(2-naphthyl)anthracene obtained from 3-1) was dissolved with 1.5 L of THF in a 5L flask and the temperature was cooled to -78C. Then, 279 ml (0.44 mol) of 1.6 M n-BuLi was slowly added dropwise thereto. After one hour, 140 g (0.74 mol) of B(OiPr)3 was slowly added dropwise thereto and the temperature was raised to room temperature and the mixture was stirred. 1 L of 2N HCl(aq) was added to the resultant mixture at a temperature of 0C and then the mixture was extracted using EA. An organic layer was dried over MgSO4 and then re-crystallized with EA/hexane, thereby producing 2-bromo-9,10-di(2-naphthyl)anthracene (150 g, 84%).
  • 4
  • [ 474688-76-1 ]
  • [ 1257220-47-5 ]
  • 5-(9,10-di(naphthalen-2-yl)anthracen-2-yl)-7,7-di-methyl-5,7-dihydroindeno[2,1-b]carbazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
53% With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium tert-butylate; palladium diacetate; In 1,3,5-trimethyl-benzene; for 8h;Reflux; Inert atmosphere; In a three-necked flask,2-bromo-9,10-di(2-naphthyl)anthracene (0.53 g, 1.05 mmol) was added,Intermediate 2-2 (0.30 g, 1.05 mmol), potassium tert-butoxide (0.22 g, 2 mmol), palladium acetate (10 mg), S-phos (36 mg) and 30 ml1,3,5-Trimethylbenzene is heated under reflux with nitrogen for 8 hours, cooled, washed with water and dried. The crude product is purified by column chromatography to give 0.4 g of product.Product, yield, 53%
  • 5
  • [ 474688-76-1 ]
  • [ 121-43-7 ]
  • [ 7732-18-5 ]
  • [ 867044-28-8 ]
YieldReaction ConditionsOperation in experiment
60% Under nitrogen of 2-bromo -9,10- di (naphthalene-2-yl) anthracene ( 10g , 1.0eq ) in THF 150 ml The mixture was after n-BuLi (11.8 ml, 1.5eq) cooled to -78 to It was added slowly and stirred for 1 hour. After adding the trimethyl borate ( 3.2ml , 1.5eq ) to the reaction mixture after 2 hours cooled to 0 back extracted with MC it was added to 6M HCl . The concentrate EA: hexane = 1: 1 column separation to obtain a white solid compound 97-1 . ( 5.5g , 60 % )
  • 6
  • [ 474688-76-1 ]
  • [ 5419-55-6 ]
  • [ 7732-18-5 ]
  • [ 867044-28-8 ]
YieldReaction ConditionsOperation in experiment
61.2% While stirring a 250 ml round bottom flask, 21.60 g (0.042 mol) of compound (E-1) prepared in Synthesis 5-1 and 216 ml of THF were added.After the temperature was dropped to -78 C, 29.15 ml (0.047 mol) of n-BuLi was slowly added dropwise.After dropping, stir for 1 hour and 30 minutes,Triisopropyl borate14.62 g (0.064 mol) was added dropwise.After standing for 10 minutes, the mixture was stirred at room temperature for 1 day.When the reaction is over, add 100 ml of 2N hydrochloric acid to make it acidic, After extracting with ethyl acetate and water, and removing water with MgSO4,Concentrated. The concentrated solution was recrystallized from hexane.As a result, 12.3 g (0.03 mol, yield 61.2%) of a white solid was obtained.
 

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