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Chemical Structure| 162364-72-9 Chemical Structure| 162364-72-9

Structure of 162364-72-9

Chemical Structure| 162364-72-9

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Product Details of [ 162364-72-9 ]

CAS No. :162364-72-9
Formula : C16H13ClN2O2
M.W : 300.74
SMILES Code : C(C1=CC=CC=C1)OC2=C(C=C3C(=C2)N=CN=C3Cl)OC
MDL No. :MFCD04115120
InChI Key :LBGIYCBNJBHZSZ-UHFFFAOYSA-N
Pubchem ID :10661998

Safety of [ 162364-72-9 ]

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

Computational Chemistry of [ 162364-72-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 21
Num. arom. heavy atoms 16
Fraction Csp3 0.12
Num. rotatable bonds 4
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 82.02
TPSA ?

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

44.24 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.1
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

3.94
Log Po/w (WLOGP)?

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

3.72
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.

2.59
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

3.98
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.47

Water Solubility

Log S (ESOL):?

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

-4.49
Solubility 0.00981 mg/ml ; 0.0000326 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.

-4.57
Solubility 0.00812 mg/ml ; 0.000027 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

-6.72
Solubility 0.0000569 mg/ml ; 0.000000189 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

Yes
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.34 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

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

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)

2.14

Application In Synthesis of [ 162364-72-9 ]

* 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.

  • Downstream synthetic route of [ 162364-72-9 ]

[ 162364-72-9 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 84478-72-8 ]
  • [ 162364-72-9 ]
  • 7-benzyloxy-4-(4-chloro-2-fluoro-5-hydroxyanilino)-6-methoxyquinazoline hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% In isopropyl alcohol; The starting material was prepared as follows: A mixture of <strong>[84478-72-8]4-chloro-2-fluoro-5-hydroxyaniline</strong> (2.5 g, 15 mmol), (as described in EP 61741 A2), and 7-benzyloxy-4-chloro-6-methoxyquinazoline (4.2 g, 14 mmol), (prepared as described for the starting material in Example 4 but with an aqueous work up), in isopropanol was heated at reflux for 2 hours. The mixture was then allowed to cool and the solid product collected by filtration, washed with isopropanol and dried to give 7-benzyloxy-4-(4-chloro-2-fluoro-5-hydroxyanilino)-6-methoxyquinazoline hydrochloride (4.8 g, 81%). 1H NMR Spectrum: (DMSOd6) 3.98(s, 3H); 5.18(s, 2H); 7.05(d, 1H); 7.18-7.27(m, 7H); 8.06(s, 1H); 8.38(s, 1H)
  • 2
  • [ 649736-31-2 ]
  • [ 162364-72-9 ]
  • [ 1022112-47-5 ]
YieldReaction ConditionsOperation in experiment
67% Preparation of l-(3-H"7-(benzyloxy)-6-methoxyquinazolin-4-ylloxyl-2-fluoro-6- nitrophenvDacetone l-(2-Fluoro-3-hydroxy-6-nitrophenyl)-propan-2-one (4.286 g) was suspended in acetonitrile(16 ml) and cooled to -5C. To the slurry was added aqueous sodium hydroxide (0.93 ml of io 46.9%w/w solution). A line wash of acetonitrile (16 ml) was applied.This cold solution was added to a solution of 7-(benzyloxy)-4-chloro-6-methoxyquinazoline (4.26 g) in anisole (28.8 ml) at 80C over 15 minutes. A line wash of acetonitrile (16 ml) was applied. The mixture was heated at 8O0C for 21 hours. The stirrer was stopped and the lower aqueous layer separated. The upper organic layer was washed further with water (6 ml) at is 8O0C.The batch was cooled to 200C and concentrated under reduced pressure (130 mbar), allowing the batch temperature to reach 1000C, collecting 24 ml of distillate. The batch temperature was adjusted to 65C and a solution of water (4 ml) in methanol (28 ml) added. The mixture was cooled to 200C and the product filtered. The filter cake was washed with methanol (2 x20 12 ml) and dried in a vacuum oven at overnight to give l-(3-[7-(benzyloxy)-6- methoxyquinazolin-4-yl]oxy}-2-fluoro-6-nitrophenyl)acetone (4.543 g, 67% of theory). IH NMR Spectrum (400 MHz, DMSO-J6) delta ppm 2.29 (s, 3 H) 4.00 (s, 3 H) 4.27 (s, 2 H) 5.37 (s, 2 H) 7.38 (m, 1 H) 7.44 (m, 2 H) 7.53 (m, 2 H) 7.56 (s, 1 H) 7.62 (s, 1 H) 7.77 (dd, J=9.1, 7.8 Hz, IH) 8.12 (dd, J=9.05, 0.81 Hz, 1 H) 8.59 (s, 1 H)25 Mass Spectrum [M+H]+
 

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Technical Information

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