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Structure of 5433-01-2

Chemical Structure| 5433-01-2

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Product Details of [ 5433-01-2 ]

CAS No. :5433-01-2
Formula : C9H11Br
M.W : 199.09
SMILES Code : CC(C1=CC(Br)=CC=C1)C
MDL No. :MFCD01318112
InChI Key :GBSGGFCCQZUXNB-UHFFFAOYSA-N
Pubchem ID :138499

Safety of [ 5433-01-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 5433-01-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.33
Num. rotatable bonds 1
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 48.72
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.

2.66
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

4.17
Log Po/w (WLOGP)?

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

3.57
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.

3.98
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

3.47
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.57

Water Solubility

Log S (ESOL):?

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

-4.08
Solubility 0.0166 mg/ml ; 0.0000833 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

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

-3.88
Solubility 0.0263 mg/ml ; 0.000132 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

-4.08
Solubility 0.0167 mg/ml ; 0.0000838 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

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

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.

-4.55 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

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)

1.31

Application In Synthesis of [ 5433-01-2 ]

* 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 [ 5433-01-2 ]

[ 5433-01-2 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 5433-01-2 ]
  • [ 216019-28-2 ]
  • 2
  • [ 5433-01-2 ]
  • [ 5369-19-7 ]
  • [ 782504-35-2 ]
YieldReaction ConditionsOperation in experiment
88% With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; In toluene; for 12h;Heating / reflux; Preparation Example 1-1: Preparation of 4-t-butyl-N- (4- isopropylphenyl ) benzenamine; As represented below in Reaction Scheme 1, 25g of 3-t- butylaniline (0.125mol) and 37.3g of 3-bromoisopropylbenzene(0.25mol) were dissolved in 25OmL of toluene, and 3.43g ofPd2(dba)3 (0.0037mol) was added thereto under a nitrogen atmosphere. Then, 14.4g of NaOBufc (0.15mol) and 1.157g of (t- Bu)3P (0.0075mol) were added to the reaction solvent, and the reaction mixture was refluxed and stirred for 12 hours. The reaction mixture was checked for the completion of the reaction by means of TLC, and if the reaction was completed, the reaction product was cooled down to room temperature. The reacted solution was poured onto a thin silica pad to perform short chromatography, and then was washed with methylene chloride (MC) . The washed solution was subjected to distillation under reduced pressure to thereby remove the solvent, and was chromatographed using n-hexane to thereby obtain a desired white solid product (29.4g, 88percent). [Reaction Scheme 1]
  • 3
  • [ 5419-55-6 ]
  • [ 5433-01-2 ]
  • [ 216019-28-2 ]
YieldReaction ConditionsOperation in experiment
Preparation of sulfonyl chlorides:Preparation of 5-(3-Isopropyl-phenyl)-pyridine-2-sulfonyl chloride; 3-Isopropyl-phenylboronic acid; n-BuLi (7.7 mL, 14.0 mmol) was added dropwise to a stirred solution of 1-bromo-3-isopropyl-benzene (2.4 g, 12.1 mmol) in dry THF (40 mL) over 30 min at -70 C. under nitrogen. The reaction mixture was degassed for 15 min, and triisopropylborate (2.63 g, 14.0 mmol) was added at the same temperature. The reaction mixture was gradually warmed to 0 C. during 90 min and stirred for an additional 30 min at 0 C. The reaction mixture was then cooled to -20 C., and an aqueous solution of 2N HCl (20 mL) was added slowly. THF was distilled off and the reaction mixture was extracted with ethyl acetate (2×20 mL). The combined organic layers were dried over Na2SO4, and concentrated in vacuo to obtain the crude product (1.85 g, 93.5%), which was used for the next step without further purification.
  • 4
  • [ 5433-01-2 ]
  • [ 78191-00-1 ]
  • [ 40428-87-3 ]
YieldReaction ConditionsOperation in experiment
66% Into a 500-mL round-bottom flask purged and maintained with an inert atmosphere of N2 was placed a solution of 1-bromo-3- (propan-2-yl)benzene (5.0 g, 25.11 mmol, 1.00 equiv) in THF (250 mL). This was followed by the addition of n-BuLi (20 mL, 2.00 equiv) dropwise with stirring at -60 C. The mixture was stirred at -60C for 30 mm. To this was added N-methoxy-N-methylacetamide (3.9 g, 37.82 mmol, 1.50 equiv) dropwise with stirring at -30 C. The resulting solution was stirred for 3 h at -30 C in a liquid N2 bath. The reaction was then quenched by the addition of 20 mL of water. The resulting solution was diluted with 200 mL of EtOAc, washed with 2x100 mL of brine, dried over anhydrous Na2SO4 and concentrated under vacuum. The residue was applied onto a silica gel column with EtOAc/petroleum ether (1:10). This resulted in 2.7 g (66%) of the title product as colorless oil.
To a solution of 1 -bromo-3-isopropylbenzene (10 g, 0.05 moi) in THF was added dropwise with BuLi (47 ml,, 0.075 niol) at -60 'C. After stirred 30 minutes, N-methoxy-N-methyiacetamide (6.22 g, 0.06 mol) was added. The mixture was stirred at -30C for 3 hours. Then the mixture was quenched with H20, the mixture was partitioned between EtOAc and water. The layer was separated and washed with water, brine, dried over Na2SC>4, and concentrated. The residue was purified by column chromatography to obtained the titled compound. ? NMR (CHLQRQFORM-d): delta 7.85 (s, i l l ). 7.79 (dt, j = 7.6, 1 .4 Hz, 1H), 7.33 - 7.53 (m, 2H), 3.00 (dt, J - 13.8, 6.9 Hz, 1H), 1.30 (d, J - 6.7 Hz, 6H)
To a solution of l-bromo-3-isopropylbenzene (10 g, 0.05 niol) in THF was added dropwise with BuLi (47 mL, 0.075 mol) at -60C. After stirred 30 minutes, -methoxy- -methylacetamide (6,22 g, 0.06 mol) was added. The mixture was stirred at -30C for 3 hours. Then the mixture was quenched with H20, the mixture was partitioned between EtOAc and water. The layer was separated and washed with water, brine, dried over Na2S04, and concentrated. The residue was purified by column chromatography to obtained the titled compound. 'H NMR (CHLOR OFQRM-d) : delta 7.85 (s, 1H), 7.79 (dt, J = 7.6, 1.4 Hz, 1H), 7.33 - 7.53 (m, 2H), 3.00 (dt, J - 13.8, 6.9 Hz, 1H), 1.30 (d, J - 6.7 Hz, 6H) LC-MS : m/z 163(M+H)+
To a solution of Compound 59A (3.96 g, 20 mmol) in dry THF (20 mL) at - 78 C was dropped a solution of n-BuLi in THF (2.5 M, 8 mL, 18 mmol). After stirred at - 78 C for 1 hour, to the mixture was dropped N-methoxy-N-methylacetamide (1.87 g, 18 mmol). The mixture was stirred at -78 C for 0.5 hour, quenched with water (10 mL), and extracted with ethyl acetate (20 mL x 3). The combined organic layers was washed with brine (40 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified with flash column chromatography on silica gel (ethyl acetate in petroleum ether, from 0% to 8% v/v) to yield Compound 59B: LC-MS (ESI) m/z: 163 [M+H]+;1H-NMR (CDCl3, 400 MHz): delta (ppm) 1.27 (d, J =7.2.4 Hz, 6H), 2.60 (s, 3H), 2.93-3.00 (m, 1H), 7.38 (t, J = 7.6 Hz, 1H), 7.44 (t, J = 7.2Hz, 1H), 7.76 (d, J = 7.2 Hz, 1H), 7.83 (s, 1H).

 

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