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Chemical Structure| 79491-45-5 Chemical Structure| 79491-45-5

Structure of 79491-45-5

Chemical Structure| 79491-45-5

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Product Details of [ 79491-45-5 ]

CAS No. :79491-45-5
Formula : C6H5Br2NO
M.W : 266.92
SMILES Code : COC1=CC=C(Br)N=C1Br
MDL No. :MFCD26743441
InChI Key :JFWDQTIVECPBDE-UHFFFAOYSA-N
Pubchem ID :11334637

Safety of [ 79491-45-5 ]

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

Computational Chemistry of [ 79491-45-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.17
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 46.13
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.

2.35
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

2.87
Log Po/w (WLOGP)?

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

2.62
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.

1.67
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

2.71
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.44

Water Solubility

Log S (ESOL):?

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

-3.68
Solubility 0.0556 mg/ml ; 0.000208 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.

-2.99
Solubility 0.271 mg/ml ; 0.00101 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

-3.86
Solubility 0.037 mg/ml ; 0.000139 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.

-5.89 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

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<0.0
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)

2.06

Application In Synthesis of [ 79491-45-5 ]

* 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 [ 79491-45-5 ]

[ 79491-45-5 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 79491-45-5 ]
  • [ 79491-46-6 ]
YieldReaction ConditionsOperation in experiment
42% With sulfuric acid; nitric acid; at 0 - 65℃; for 2.0h; Nitric acid (red fuming, 90%; 16 mL, 318 mmol; Aldrich, St. Louis, MO) was added to conc. H2SO4(16 mL) at 0 C, and 2,6-dibromo-3-methoxypyridine (3.4 g, 13 mmol) was added to the resulting solution in portions over 20 min. A reflux condenser was attached to the reaction vessel, and the reaction solution was allowed to warm to ambient temperature before being heated to 65 C for 2 h. The reaction mixture was subsequently poured onto ice in a 500-mL beaker. After the ice melted, the resulting mixture was vacuum filtered, and the collected solid was rinsed with a small amount of water and dried in vacuo to furnish 2,6-dibromo-3-methoxy-5-nitropyridine (1.67 g, 5.4 mmol, 42% yield) as a light-yellow solid.
31% With sulfuric acid; nitric acid; potassium nitrate; at 0 - 65℃; To conc H2SO4 (15 ml) at 0 C were added nitric acid (67%, 4.0 mL) and KNO3 (2.0 g) followed by Compound 137 (2.0 g, 7.5 mmol). The reaction mixture was stirred at 65 C overnight, after which it was poured into crushed ice and neutralized carefully with solid Na2C03, then extracted with EtOAc (2 times). The combined organic extracts were concentrated, and the resulting residue was purified by flash silica gel chromatography (0-80% of EtOAc in hexanes) to give Compound 138 (732 mg, 31% yield).
28% With sulfuric acid; nitric acid; at 0 - 65℃; for 36.0h; 5.42 2,6-Dibromo-3-methoxy-5-nitropyridine (32) Fuming nitric acid (16 M, 5 mL, 80 mmol) was added to a solution of 31 (2.0 g, 7.5 mmol) in sulfuric acid (18 M, 8 mL, 144 mmol) at 0 C, and then the mixture was heated at 65 C for 18 h. Additional concd nitric acid (2.5 mL, 40 mmol) was added and the reaction mixture was stirred at 65 C for a further 18 h. The reaction mixture was cooled and cautiously neutralised with solid sodium carbonate. The resulting mixture was extracted with ethyl acetate (3 * 50 mL), and the combined organic extracts were dried and concentrated under reduced pressure. The residue was purified by chromatography on a silica cartridge (100 g) eluting with a gradient of 0-25% ethyl acetate-cyclohexane over 60 min. The appropriate fractions were combined and evaporated under reduced pressure to give 32 (0.69 g, 28%) as a white solid: 1H NMR (400 MHz, DMSO-d6) delta = 8.24 (s, 1H), 4.00 (s, 3H); LCMS (System A) RT = 1.05 min, 98%, no mass ions observed in either +ve or -ve mode.
With sulfuric acid; nitric acid; In water; at 0 - 65℃; E3. 2,6-Dibromo-3-methoxy-5-nitropyridine To 150 ml of concentrated sulfuric acid is added at 0 C 150 ml fuming nitric acid. 40.0 g of 2,6-dibromo-3-methoxypyridine (example E2) is added portionwise to this mixture at 0 C. The reaction mixture is stirred for 45 minutes at 0 C and then heated to 65 C for 2 h. The mixture is poured into 2 l of crushed ice and stored at 0 C overnight. The resulting precipitate is filtered, washed with water and dried under vacuum to yield the title compound. 1H NMR (400 MHz, CDCl3): delta = 4.01 (s, 3H), 7.63 (s, 1 H).

 

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Technical Information

Categories

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