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Chemical Structure| 552331-05-2 Chemical Structure| 552331-05-2

Structure of 552331-05-2

Chemical Structure| 552331-05-2

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Product Details of [ 552331-05-2 ]

CAS No. :552331-05-2
Formula : C9H4BrCl2N
M.W : 276.94
SMILES Code : ClC1=CC2=C(C(Cl)=N1)C=CC(Br)=C2
MDL No. :MFCD09258639
InChI Key :YRSSIZNHQQNESH-UHFFFAOYSA-N
Pubchem ID :16218370

Safety of [ 552331-05-2 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H301-H315-H318-H335-H413
Precautionary Statements:P261-P280-P301+P310-P305+P351+P338
Class:8(6.1)
UN#:2923
Packing Group:

Computational Chemistry of [ 552331-05-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 10
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 59.46
TPSA ?

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

12.89 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.61
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

4.72
Log Po/w (WLOGP)?

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

4.3
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.

3.66
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

4.37
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.93

Water Solubility

Log S (ESOL):?

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

-5.1
Solubility 0.0022 mg/ml ; 0.00000795 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.

-4.72
Solubility 0.00528 mg/ml ; 0.0000191 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

-5.78
Solubility 0.000456 mg/ml ; 0.00000165 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

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

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.

-4.64 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

1.0
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

1.0 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)

1.77

Application In Synthesis of [ 552331-05-2 ]

* 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.

  • Upstream synthesis route of [ 552331-05-2 ]

[ 552331-05-2 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 552331-05-2 ]
  • [ 552331-06-3 ]
YieldReaction ConditionsOperation in experiment
68.4% at 120℃; for 5 h; Add 50 g of 1,3-dichloro-6-bromoisoquinoline to 500 mL of glacial acetic acid, and then add 14 g of red phosphorus.Hydrochloric acid 100 mL, then the system was heated to reflux, the reaction was about 5 h, and TLC confirmed the reaction was complete.After-treatment: cool to room temperature, suction filtration, add 500 mL of water to the filter cake.The mixture was adjusted to pH = 8 with 15percent aqueous ammonia, filtered, and the filtrate was extracted with ethyl acetate.The acetic acid phase is dried, added with water and alkali, extracted with ethyl acetate, and combined with all organic phases.Wash once with saturated brine, dry over anhydrous sodium sulfate, spin dry,The column was passed through 200-300 mesh silica gel, petroleum ether: ethyl acetate = 50:1 to 20:1.The product 3-chloro-6-bromoisoquinoline 30 g was obtained in a yield of 68.4percent.
50% With HI In acetic acid; ethyl acetate Example 80C
6-Bromo-3-chloro-isoquinoline
A mixture of Example 80B (1.8 g, 6.5 mmol), P (0.48 g, 15.5 mmol) and HI (3 ml, 48percent) in acetic acid (20 ml) was refluxed for 8 hours, filtrated under hot condition and concentrated under vacumm.
The residue was basified by adding sodium hydroxide solution, treated with ethyl acetate (200 mL), washed with brine, dried (MgSO4), filtered, and concentrated.
The concentrate was purified by flash column chromatography on silica gel with 30percent ethyl acetate/hexane to provide the title compound (0.81 g, 50percent). MS (DCI/NH3) m/e 244 (M+H)+.
50%
Stage #1: With phosphorus; hydrogen iodide In water; acetic acid for 8 h; Heating / reflux
Stage #2: With sodium hydroxide In water
Example 80C
6-Bromo-3-chloro-isoquinoline
A mixture of Example 80B (1.8 g, 6.5 mmol), P (0.48 g, 15.5 mmol) and HI (3 ml, 48percent) in acetic acid (20 ml) was refluxed for 8 hours, filtrated under hot condition and concentrated under vacumm.
The residue was basified by adding sodium hydroxide solution, treated with ethyl acetate (200 mL), washed with brine, dried (MgSO4), filtered, and concentrated.
The concentrate was purified by flash column chromatography on silica gel with 30percent ethyl acetate/hexane to provide the title compound (0.81 g, 50percent). MS (DCI/NH3) m/e 244 (M+H)+.
References: [1] Patent: CN108929270, 2018, A, . Location in patent: Paragraph 0017; 0019; 0022; 0024; 0027; 0029; 0032; 0034.
[2] Patent: US2003/187026, 2003, A1, .
[3] Patent: US2003/199511, 2003, A1, . Location in patent: Page/Page column 34-35.
 

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