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Structure of 128272-29-7

Chemical Structure| 128272-29-7

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Product Details of [ 128272-29-7 ]

CAS No. :128272-29-7
Formula : C20H21BrO
M.W : 357.28
SMILES Code : OC1=C(C2(C3)CC4CC3CC(C4)C2)C=C5C=C(Br)C=CC5=C1
MDL No. :MFCD13182367
InChI Key :BLOOFHRWAOQRNT-UHFFFAOYSA-N
Pubchem ID :14549072

Safety of [ 128272-29-7 ]

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

Computational Chemistry of [ 128272-29-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 22
Num. arom. heavy atoms 10
Fraction Csp3 0.5
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 95.44
TPSA ?

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

20.23 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.6
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

6.91
Log Po/w (WLOGP)?

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

5.78
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.

5.3
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

5.36
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

5.39

Water Solubility

Log S (ESOL):?

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

-6.68
Solubility 0.0000748 mg/ml ; 0.000000209 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.

-7.15
Solubility 0.0000255 mg/ml ; 0.0000000714 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

-6.37
Solubility 0.000152 mg/ml ; 0.000000426 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

High
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

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

Yes
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.

-3.57 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

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

0.0 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)

4.33

Application In Synthesis of [ 128272-29-7 ]

* 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 [ 128272-29-7 ]

[ 128272-29-7 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 128272-29-7 ]
  • [ 100-39-0 ]
  • [ 170355-91-6 ]
YieldReaction ConditionsOperation in experiment
In ethanol; N,N-dimethyl-formamide; (a) Preparation of 7-(1-adamantyl)-6-benzyloxy-2-bromonaphthalene 1.26 g (42 mmol) of sodium hydride (80% in oil) and 50 ml of DMF were introduced into a 3-necked flask, a solution of 12.5 g (35 mmol) of <strong>[128272-29-7]7-(1-adamantyl)-6-hydroxy-2-bromonaphthalene</strong> in 100 ml of DMF was added dropwise and stirring was carried out until gas evolution had ceased. 5 ml (42 mmol) of benzyl bromide were then added and stirring was carried out at room temperature for 2 hours. The reaction mixture was poured into water and extracted with ethyl ether and the organic phase was separated by settling, dried over magnesium sulfate and evaporated. The residue obtained was taken up in ethanol, heated to reflux, cooled, filtered and dried. 12.5 g (80%) of the expected compound were collected, which compound had a melting point of 150-1 C.
(a) Preparation of 7-(1-adamantyl)-6-benzyloxy-2-bromonaphthalene Following the basic procedure of Example 11, by reacting 12.5 g (35 mmol) of <strong>[128272-29-7]7-(1-adamantyl)-6-hydroxy-2-bromonaphthalene</strong> with 5 ml (42 mmol) of benzyl bromide, 12.5 g (80%) of the expected compound of melting point 150-151 C. were obtained.
  • 2
  • [ 128272-29-7 ]
  • [ 459-46-1 ]
  • 7-(1-adamantyl)-6-(4-fluorobenzyl)oxy-2-bromonaphthalene [ No CAS ]
YieldReaction ConditionsOperation in experiment
(a) Preparation of 7-(1-adamantyl)-6-(4-fluorobenzyl)oxy-2-bromonaphthalene Following the procedure of Example 1(a), but reacting 1.1 g (3 mmol) of <strong>[128272-29-7]7-(1-adamantyl)-6-hydroxy-2-bromonaphthalene</strong> with 420 mul (3.3 mmol) of 4-fluorobenzyl bromide, 1.2 g (86%) of the expected compound were obtained in the form of a colorless oil.
(a) Preparation of 7-(1-adamantyl)-6-(4-fluorobenzyl)oxy-2-bromonaphthalene Following the basic procedure of Example 11, by reacting 1.1 g (3 mmol) of <strong>[128272-29-7]7-(1-adamantyl)-6-hydroxy-2-bromonaphthalene</strong> with 420 mul (3,3 mmol) of 4-fluorobenzyl bromide, 1.2 g (86%) of the expected compound was obtained in the form of a colorless oil.
  • 3
  • [ 15231-91-1 ]
  • [ 768-95-6 ]
  • [ 128272-29-7 ]
YieldReaction ConditionsOperation in experiment
With sulfuric acid; In diethyl ether; n-heptane; dichloromethane; (a) Preparation of 3-(1-adamantyl)-6-bromo-2-naphthol 56 g (0.25 mol) of 6-bromo-2-naphthol, 38.2 g (0.25 mol) of 1-adamantanol and 500 ml of a mixture of dichloromethane and heptane (40/60) were introduced into a round-bottomed flask. 15 ml of concentrated sulfuric acid were added and the reaction mixture was stirred at room temperature for 48 hours. The solid was filtered off, washed with heptane (3*100 ml) and dissolved in ethyl ether and the organic phase was washed with water, separated by settling, dried over magnesium sulfate and evaporated. 60.1 g (67%) of the expected compound were collected, which compound had a melting point of 215-6 C.
With hydrogenchloride; In n-heptane; dichloromethane; water; (a) Synthesis of 7-(1-adamantyl)-6-hydroxy-2-bromonaphthalene: 22.3 g (0.1 mol) of 6-bromo-2-naphthol, 15.2 g (0.1 mol) of 1-adamantanol and 100 ml of dichloromethane were introduced into a round-bottomed flask. 5.5 ml of concentrated hydrochloric acid were added and the mixture was stirred at room temperature for twelve hours. The mixture was evaporated to dryness and the residue was taken up in water and neutralized with sodium bicarbonate. The resulting mixture was extracted with ethyl acetate and the organic phase was separated out after settling of the phases had taken place, dried over magnesium sulfate and evaporated. The residue obtained was triturated in a mixture of dichloromethane and heptane (30/70), filtered and dried. 19 g (53%) of the expected compound, with a melting point of 215-6 C., were collected.
  • 4
  • [ 128272-29-7 ]
  • [ 629-04-9 ]
  • 7-(1-adamantyl)-6-heptyloxy-2-bromonaphthalene [ No CAS ]
YieldReaction ConditionsOperation in experiment
(a) Preparation of 7-(1-adamantyl)-6-heptyloxy-2-bromonaphthalene Following the procedure of Example 8(b), but reacting 3.4 g (9.5 mmol) of 3-(1-adamantyl)-6-bromo-2-naphthol with 2.05 g (11.4 mmol) of 1-bromoheptane, 3.4 g (79%) of 7-(1-adamantyl)-6-heptyloxy-2-bromonaphthalene were obtained.
  • 5
  • [ 128272-29-7 ]
  • [ 18162-48-6 ]
  • 7-(1-adamantyl)-6-tert-butyldimethylsilyloxy-2-bromonaphthalene [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap; triethylamine; In N,N-dimethyl-formamide; Preparation of 7-(1-adamantyl)-6-tert-butyldimethylsilyloxy-2-bromonaphthalene 11.9 g (33.3 mmol) of <strong>[128272-29-7]7-(1-adamantyl)-6-hydroxy-2-bromonaphthalene</strong>, 120 ml of DMF, 5.1 ml (36.6 mmol) of triethylamine and 203 mg of 4-dimethylaminopyridine were introduced successively into a three-necked flask. A solution of 5.52 g (36.6 mmol) of tert-butyldimethylsilyl chloride was added dropwise and the mixture was stirred at room temperature for 12 hours. The reaction medium was poured into water, extracted with ethyl ether, the organic phase decanted, dried over magnesium sulfate and evaporated. The residue obtained was purified by chromatography on a silica column eluted with heptane; 12 g (76%) of 7-(1-adamantyl)-6-tert-butyldimethylsilyloxy-2-bromonaphthalene of melting point 120-121 C. were recovered.
  • 6
  • [ 15231-91-1 ]
  • [ 22635-62-7 ]
  • [ 128272-29-7 ]
YieldReaction ConditionsOperation in experiment
With sulfuric acid; In hexane; n-heptane; water; ethyl acetate; EXAMPLE 9 Preparation of 7-(1-adamantyl)-6-hydroxy-2-bromonaphthalene In a 100 ml flask, under a nitrogen atmosphere, are placed 2 g of 1-acetoxyadamantane and 20 ml of n-heptane, and 0.5 g of concentrated sulfuric acid is introduced drop by drop. At a temperature of about 22.C, 2.3 of 6-hydroxy-2-bromonaphthalene are added slowly and the mixture is left in vigorous agitation. The solvent is eliminated by filtration and the solid residue in suspension in the water is collected. The residue is filtered and then washed until neutrality is obtained. The resulting reddish solid is washed again with hexane until a colorless filtrate is obtained. After drying in a vacuum oven for 24 hours at 30 C one obtains a raw product which is chromatographed with a silica column using an ethyl acetate and hexane mixture of 1:9 as the eluent. After evaporation of the solvents, 1.3 g of desired raw product were obtained (Melting point: 218-224 C.).
 

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