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Chemical Structure| 874792-20-8 Chemical Structure| 874792-20-8

Structure of 874792-20-8

Chemical Structure| 874792-20-8

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Product Details of [ 874792-20-8 ]

CAS No. :874792-20-8
Formula : C10H8BrNO
M.W : 238.08
SMILES Code : COC1=CC=NC2=CC=C(Br)C=C12
MDL No. :MFCD04036192
InChI Key :AWLGLUBASOBKNM-UHFFFAOYSA-N
Pubchem ID :45790929

Safety of [ 874792-20-8 ]

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

Computational Chemistry of [ 874792-20-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 10
Fraction Csp3 0.1
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 55.94
TPSA ?

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

22.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.43
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

2.85
Log Po/w (WLOGP)?

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

3.01
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.

2.19
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

3.1
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.72

Water Solubility

Log S (ESOL):?

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

-3.61
Solubility 0.0578 mg/ml ; 0.000243 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.

-2.97
Solubility 0.253 mg/ml ; 0.00106 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

-4.69
Solubility 0.00489 mg/ml ; 0.0000206 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

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.

-5.73 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)

1.49

Application In Synthesis of [ 874792-20-8 ]

* 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 [ 874792-20-8 ]

[ 874792-20-8 ] Synthesis Path-Downstream   1~10

  • 1
  • [ 65340-70-7 ]
  • [ 124-41-4 ]
  • [ 874792-20-8 ]
YieldReaction ConditionsOperation in experiment
90.8% In methanol; at 20 - 120℃; for 15h; To a solution of 6-bromo-4-chloro-quinoline (12.12 g, 50 mmol) in methanol (200 mL) was added sodium methoxide (13.50 g, 250 mmol) at room temperature. Then, the reaction mixture was heated to 120 C. for 15 h in a sealed reaction flask. After cooling to room temperature, the methanol was removed under the vacuum and the residue was diluted with water. Then, the solids were collected by filtration and washed with water. After drying in air, 10.8 g (90.8% yield) of 6-bromo-4-methoxy-quinoline was isolated as a white solid which can be crystallized from acetonitrile: EI-HRMS m/e calcd for C10H8BrNO (M+) 236.9789, found 236.9784.
36% In methanol; at 120℃; for 1h;Microwave irradiation; 300 mg (1.24 mmol) of 6-bromo-4-chloroquinoline [Lin et al., J. Med. Chem. 1978, 21, 268] was taken up in 4 ml methanol and 1.15 ml (6.19 mmol) methanolic sodium methylate solution (30 wt.%) was added. Then it was reacted in a single mode microwave for 1 h at 1200C. The solvent was removed in a rotary evaporator and the residue was partitioned between water and ethyl acetate. The aqueous phase was extracted with ethyl acetate and the combined organic phases were dried over magnesium sulfate. The solvent was removed by distillation at reduced pressure. In this way we obtained 150 mg (36% of theor.) of the target compound.LC-MS (method 2): R, = 1.24 min; MS (EIpos): m/z = 238 [M]+.
  • 2
  • [ 874792-20-8 ]
  • [ 73183-34-3 ]
  • [ 1210048-04-6 ]
YieldReaction ConditionsOperation in experiment
With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; at 110℃;Inert atmosphere; Under an argon atmosphere, 150 mg of example 87A was dissolved in 4 ml dioxane. Then 111.3 mg (1.134 mmol) potassium acetate, 41.2 mg (0.050 mmol) of 1, l'-bis-(diphenylphosphino)- ferrocene palladium(II) chloride-dichloromethane complex and 176 mg (0.693 mmol) of 4,4,4'4'5,5,5'5'-octamethyl-2,2'-bi-l,3,2-dioxaborolan were added. The reaction mixture was stirred overnight at 1100C oil bath temperature. After cooling, dichloromethane was added to the reaction mixture and it was filtered on kieselguhr. It was washed again with ethyl acetate. The filtrate was concentrated in a rotary evaporator at reduced pressure and dried under high vacuum. We obtained 227 mg of 4-methoxy-6-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)quinoline [47%, (LC-MS)] as raw product. This was reacted subsequently without further purification.
  • 3
  • [ 874792-20-8 ]
  • [ 68-12-2 ]
  • [ 879323-73-6 ]
YieldReaction ConditionsOperation in experiment
64% To a solution of <strong>[874792-20-8]6-bromo-4-methoxy-quinoline</strong> (8.91 g, 37.42 mmol) in THF (tetrahydrofuran) (155 mL) was added dropwise a 2.5M solution of n-butyllithium in hexanes (16.46 mL, 4.16 mmol, 1.1 equiv.) at -70 C. During the addition, the temperature of the reaction mixture was raised slightly to -60 C. and it gave a very dark brown solution. The resulting colored solution was stirred for 30 min at this temperature. Then, a solution of dimethylformamide (5.78 mL, 74.84 mmol) in THF (10 mL) was added dropwise. After addition, the mixture was allowed to warm to room temperature and stirred for 15 h. Then, the mixture was diluted with saturated ammonium chloride solution and the two layers were separated. The aqueous layer was extracted with ethyl acetate (3*1 50 mL). The combined organic extracts were washed with brine solution and dried over anhydrous magnesium sulfate. Filtration of the drying agent and removal of the solvent under the vacuum gave the crude brown solid. This solid was dissolved in acetonitrile (~50 mL) at hot condition and then stored in the refrigerator overnight. The solids were collected by filtration and washed with diethyl ether. After drying in air, 4.47 g (64% yield) of 4-methoxy-quinoline-6-carbaldehyde was isolated as a white solid: EI-HRMS m/e calcd for C11H9NO2 (M+) 187.0633, found 187.0638.
  • 5
  • [ 67-56-1 ]
  • [ 65340-70-7 ]
  • [ 124-41-4 ]
  • [ 874792-20-8 ]
YieldReaction ConditionsOperation in experiment
at 100℃; for 1h; A 5 mL microwave vial was charged with 4-chloro-6-bromoquinoline (0.15 g, 0.62 mmol) and a 25 wt % solution of sodium methoxide in methanol (2.0 mL, 8.8 mmol). The vial was sealed and heated to 100C for 60 minutes under microwave irradiation (Biotage, Initiator). After cooling, the solvent was removed in vacuo, the residue washed with water, filtered and dried via .yophilization to obtain 6-bromo-4-methoxyquinoline.LRMS (ESI) calc'd for C10H9BrNO [M+H]+: 238, Found: 238.
  • 6
  • [ 145369-94-4 ]
  • [ 874792-20-8 ]
  • 7
  • [ 874792-20-8 ]
  • [ 608-31-1 ]
  • N-(2,6-dichlorophenyl)-4-methoxyquinolin-6-amine [ No CAS ]
  • 8
  • [ 874792-20-8 ]
  • N-(2,6-dichlorophenyl)-4-methoxy-N-methylquinolin-6-amine [ No CAS ]
  • 9
  • [ 927801-23-8 ]
  • [ 124-41-4 ]
  • [ 874792-20-8 ]
  • 10
  • [ 874792-20-8 ]
  • [ 1083326-73-1 ]
  • 2,4-difluoro-N-(2-methoxy-5-(4-methoxyquinolin-6-yl)pyridin-3-yl)benzenesulfonamide [ No CAS ]
 

Historical Records

Technical Information

Categories

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