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Structure of 886762-39-6

Chemical Structure| 886762-39-6

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Product Details of [ 886762-39-6 ]

CAS No. :886762-39-6
Formula : C6H4Cl2FN
M.W : 180.01
SMILES Code : NC1=CC=C(Cl)C(Cl)=C1F
MDL No. :MFCD04039241
Boiling Point : No data available
InChI Key :ZPTBUEKFZSYXBD-UHFFFAOYSA-N
Pubchem ID :2782703

Safety of [ 886762-39-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H312-H332
Precautionary Statements:P280

Computational Chemistry of [ 886762-39-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 40.82
TPSA ?

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

26.02 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.68
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

3.15
Log Po/w (WLOGP)?

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

3.14
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.

3.1
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

2.84
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.78

Water Solubility

Log S (ESOL):?

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

-3.38
Solubility 0.0743 mg/ml ; 0.000413 mol/l
Class?

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

Soluble
Log S (Ali)?

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

-3.37
Solubility 0.0774 mg/ml ; 0.00043 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

-3.55
Solubility 0.051 mg/ml ; 0.000283 mol/l
Class?

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

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

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

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.

-5.16 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

2.0 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)

1.7

Application In Synthesis of [ 886762-39-6 ]

* 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 [ 886762-39-6 ]

[ 886762-39-6 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 886762-39-6 ]
  • [ 179688-53-0 ]
  • [ 1429757-64-1 ]
YieldReaction ConditionsOperation in experiment
83% <strong>[179688-53-0]7-methoxy-4-oxo-3,4-dihydroquinazolin-6-yl acetate</strong> (100 g) was added to toluene (850 mL) and NN-diisopropylethylamine (82.5 mL). Phosphorus oxychloride (100 mL) was added thereto over 20 minutes at 75C, followed by stirring for 3 hours. Toluene (450 mL) and 3,4-dichloro-2-fluoroaniline (84.6 g) were added to the resulting mixture, followed by stirring for 2 hours. Upon completion of the reaction, the resulting mixture was cooled to 25C, and the solid thus obtained was filtered under a reduced pressure and washed with toluene (400 mL). Isopropanol (1,000 mL) was added to the solid, and the resulting mixture was stirred for 2 hours. The solid thus obtained was filtered and washed with isopropanol (400 mL), and then was dried at 40C in an oven to obtain the target compound (143 g, yield: 83%). 1H-NMR (DMSO-d6, 300 MHz, ppm) δ 8.92 (s, 1H), 8.76 (s, 1H), 7.69- 7.57 (m, 3H), 4.01 (s, 3H), 2.38 (s, 3H).
83% Example 1 Preparation of 4-(3,4-dichloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yl acetate (the compound of formula (VI)) 7-methoxy-4-oxo-3,4-dihydroquinazolin-yl acetate (100 g) was added to toluene (850 ml) and N,N-diisopropylethylamine (82.5 ml). Phosphorusoxy chloride (100 ml) was added thereto over 20 minutes at 75 C., followed by stirring for 3 hours. Toluene (450 ml) and 3,4-dichloro-2-fluoroaniline (84.6 g) were added to the resulting mixture, followed by stirring for 2 hours. Upon completion of the reaction, the resulting mixture was cooled to 25 C. The solid thus obtained was filtered under a reduced pressure and washed with toluene (400 ml). Isopropanol (1,000 ml) was added to the solid, which was then stirred for 2 hours. The resulting solid was filtered and washed with isopropanol (400 ml). The solid was dried at 40 C. in an oven to produce the compound of formula (VI) (143 g, yield: 83%). 1H-NMR (DMSO-d6, 300 MHz, ppm) δ 8.92 (s, 1H), 8.76 (s, 1H), 7.69-7.57 (m, 3H), 4.01 (s, 3H), 2.38 (s, 3H).
83% 100 g of <strong>[179688-53-0]7-methoxy-4-oxo-3,4-dihydroquinazolin-6-yl acetate</strong> was added to 850 ml of toluene and 82.5 ml of N, N-diisopropylethylamine,100 ml of phosphorus oxychloride was added at 75 DEG C for 20 minutes and then stirred for 3 hours.450 ml of toluene was further added to the resulting reaction solution, 84.6 g of 3,4-dichloro-2-fluoroaniline was added, and the mixture was stirred for 2 hours. When the reaction was completed, the temperature of the reaction solution was cooled to 25 C, and the resulting solid was filtered under reduced pressure and washed with 400 ml of toluene. 1000 ml of isopropanol was added to the obtained solid, and the mixture was stirred for 2 hours. The solid was filtered and washed with 400 ml of isopropanol.The obtained solid was dried in a drying oven at 40 to obtain the title compound (143 g, yield 83%).
  • 2
  • [ 574745-97-4 ]
  • [ 886762-39-6 ]
  • [ 109384-19-2 ]
  • C20H19Cl2FN4O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
1 .43 g of the compound obtained in (1-5), 1 .91 g of (R)-(-)-N-Boc-4- hydroxypiperidine and 1 .96 g of triphenylphosphine were added to 20 ml of methylene chloride, and 2.01 ml of diisopropylazodicarboxylate was added thereto dropwise. The resulting mixture was stirred at room temperature for 1 hour and distilled under a reduced pressure, and the residue was briefly purified by columnchromatography (ethylacetate : methylenechloride : methanol = 20 :20: 1). The partially purified residue was then dissolved in 60 ml of 2-propanol, 1 .17 g of 3,4- dichloro-4-fluoroaniline was thereto, and the mixture was stirred at 1 00 00 for 3 hours. The resulting mixture was distilled under a reduced pressure to remove the solvent, and the residue was dissolved in 60 ml of methylenechloride. 60 ml oftrifluoroacetic acid was added thereto and the mixture was stirred at room temperature for 1 hour. The resulting mixture was distilled under a reduced pressure to remove the solvent. Saturated sodium bicarbonate solution was added to the resulting residue to make it basic, followed by extraction with chloroform. The organic layer was dried over anhydrous sodium sulfate, filtered, and distilled under a reduced pressure. The resulting residue was subjected to column chromatography (chloroform : methanol = 1: 2) to obtain the title compound.
 

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