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Chemical Structure| 461432-23-5

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Product Details of [ 461432-23-5 ]

CAS No. :461432-23-5
Formula : C15H14BrClO
M.W : 325.62
SMILES Code : CCOC1=CC=C(CC2=C(Cl)C=CC(Br)=C2)C=C1
MDL No. :MFCD11042292
InChI Key :ZUNCHZBITMUSRD-UHFFFAOYSA-N
Pubchem ID :9996449

Safety of [ 461432-23-5 ]

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

Computational Chemistry of [ 461432-23-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 18
Num. arom. heavy atoms 12
Fraction Csp3 0.2
Num. rotatable bonds 4
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 79.9
TPSA ?

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

9.23 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.56
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

5.5
Log Po/w (WLOGP)?

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

5.09
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.

5.01
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

5.54
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

4.94

Water Solubility

Log S (ESOL):?

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

-5.55
Solubility 0.000911 mg/ml ; 0.0000028 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.

-5.45
Solubility 0.00115 mg/ml ; 0.00000353 mol/l
Class?

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

Moderately 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

-7.29
Solubility 0.0000165 mg/ml ; 0.0000000507 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

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

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

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.

-4.38 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

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<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)

2.11

Application In Synthesis of [ 461432-23-5 ]

* 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 [ 461432-23-5 ]

[ 461432-23-5 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 461432-23-5 ]
  • [ 1461750-25-3 ]
  • C42H43ClO6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% Take 112g of compound N-9 (0.347mol, 1.25eq) and 720ml of anhydrous tetrahydrofuran and stir, replace with nitrogen three times, cool down and control the temperature -80-75, and add 240ml 1.6M n-butyllithium n-hexane solution ( 0.347mol, 1.25eq), the dripping time is 2h, after dripping, keep stirring for 1h; continue to control the temperature -80-75, add dropwise the tetrahydrofuran solution of compound N-8 (120g compound N-8 (0.277mol, 1.0eq) dissolved in 240ml tetrahydrofuran), the dripping time is 2h, after dripping, keep stirring for 2h until TLC monitors that the reaction is complete (petroleum ether: ethyl acetate=6:1 as the developing solvent, and no compound N-8. Complete); Control the temperature to below -20C, add dropwise 600ml, 10wt% ammonium chloride aqueous solution, then return to 10C, extract with 1600ml dichloromethane, take the organic phase, wash with 1500ml saturated brine, and dry with anhydrous sodium sulfate , Concentrate under reduced pressure to no cuts to obtain 250 g of compound N-10-a, which is continuously cast in step S2 at a yield of 100%.
  • 2
  • [ 461432-23-5 ]
  • [ 1461750-25-3 ]
  • C43H45ClO6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
To a 250 mL of dry round-bottom flask, 6.51 g (20 mmol) of (2-chloro-5-bromophenyl) (4-ethoxyphenyl) methane and 60 mL of dry THF are added, and the magneton is added. After purging with nitrogen gas, the mouth of the round-bottom flask is sealed with a soft rubber plug. The flask is placed in a liquid nitrogen-ethanol system to cool to -78C, and stirred. 12.5 mL of n-butyl lithium solution with a concentration of 1.6 M (20 mmol n-butyl lithium) is added slowly with a injector, , and stirred for another half an hour at this temperature after the addition, and then the solution prepared by dissolving 8.65 g (20 mmol) of M-4 in 40 mL of dry THF is added slowly with a injector. After the addition, the reaction mixture is stirred for another 1 hour at this temperature. After which, at this temperature, the solution prepared by dissolving 4.81 g (50 mmol) of methanesulfonic acid in 20 mL of methanol is added slowly with a injector, , and stirred at room temperature for 12 hours after the addition. (0266) The reaction mixture is dumped into 400 mL of ice water, stirred, the pH value is adjusted to pH = 4-6 with saturated NaHCO3 solution, and extracted with 100 mL x 3 of dichloromethane. The organic phases are combined, washed with 0.1 mol/l aqueous NaCl solution, and dried with anhydrous sodium sulfate, evaporated to dryness on the rotary evaporator, and the resulting residue is the crude product of M-5. The crude product of M-5 is analyzed using electrospray ionization-mass spectrometry (ESI-MS), the mass-charge ratio of which is m/z = 693 ([M+H]+). Wherein, the crude product can be used for the next step of reaction without purification.
  • 3
  • [ 461432-23-5 ]
  • [ 67442-07-3 ]
  • 2-chloro-1-(4-chloro-3-(4-ethoxybenzyl)phenyl)ethanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
98% To a cold solution (-78?°C) of compound 15 (470?mg, 1.45?mmol) in dry THF (3?mL) 1.6?N solution of n-BuLi in hexanes (0.13?mL) was added dropwise. The mixture was stirred at this temperature for 45?min and to this mixture a solution of <strong>[67442-07-3]2-chloro-N-methoxy-N-methylacetamide</strong> (200?mg, 1.45?mmol) in dry THF (2?mL) was added dropwise at -78?°C. Stirring was continued for 3?h?at this temperature where the consumption of the starting material was checked by TLC. Saturated aqueous solution of NH4Cl (5?mL) was then added, followed by extraction with of DCM (3?*?8 mL). The combined organic layers ware dried over Na2SO4, the solvent was removed under reduced pressure and the residue was chromatographed on a silica gel column (hexane/ethyl acetate 12:1) to give product 16 (455?mg, 98percent) as a colorless oil. FTIR (neat film) 3033, 1702, 1629?cm-1. 1H NMR (500?MHz, CDCl3) delta 7.74 (d, J?=?2.0?Hz, 1H), 7.72 (dd, J?=?8.3, 2.0?Hz, 1H), 7.47 (d, J?=?8.3?Hz, 1H), 7.09 (d, J?=?8.6?Hz, 2H), 6.83 (d, J?=?8.6?Hz, 2H), 4.58 (s, 2H), 4.07 (s, 2H), 4.00 (q, J?=?7.0?Hz, 2H), 1.40 (t, J?=?7.0?Hz, 3H). 13C NMR (126 MHz, CDCl3) delta 190.2, 157.7, 140.4, 140.2, 132.8, 130.8, 130.2, 130.1, 129.9, 127.5, 114.7, 63.4, 45.8, 38.3, 14.7. LC-MS (ESI positive) m/z: 361 [M+K]+ HRMS m/e: C17H16KO2 [(M+K)+] calcd: 361.0159, found: 361.0156.
  • 4
  • [ 67-56-1 ]
  • [ 461432-23-5 ]
  • [ 1461750-25-3 ]
  • C43H45ClO6 [ No CAS ]
 

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