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Structure of 175422-04-5

Chemical Structure| 175422-04-5

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Product Details of [ 175422-04-5 ]

CAS No. :175422-04-5
Formula : C5H2Br2N2O2
M.W : 281.89
SMILES Code : BrC1=NC(=CC(=C1)[N+](=O)[O-])Br
MDL No. :MFCD07369947
InChI Key :XIPATZUHJFQGQC-UHFFFAOYSA-N
Pubchem ID :16038748

Safety of [ 175422-04-5 ]

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

Computational Chemistry of [ 175422-04-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 48.46
TPSA ?

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

58.71 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.61
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

2.73
Log Po/w (WLOGP)?

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

2.51
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.

0.82
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

0.66
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.67

Water Solubility

Log S (ESOL):?

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

-3.65
Solubility 0.0638 mg/ml ; 0.000226 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.

-3.62
Solubility 0.0681 mg/ml ; 0.000242 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

-3.11
Solubility 0.221 mg/ml ; 0.000783 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

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

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.

-6.08 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

3.0 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)

2.29

Application In Synthesis of [ 175422-04-5 ]

* 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 [ 175422-04-5 ]

[ 175422-04-5 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 124-41-4 ]
  • [ 175422-04-5 ]
  • [ 117873-72-0 ]
YieldReaction ConditionsOperation in experiment
70% With methanol; In tetrahydrofuran; at 20℃; for 2h; To a solution of compound S1 (2 g, 7.11 mmol) in THF (15 mL) was added MeONa/MeOH solution (1.2 mL, 6.05 mmol, 1.3 M). The reaction was stirred at room temperature for 2 hrs and quenched with water. The resulting mixture was extracted with EtOAc twice. The combined organic phases were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to dryness. The residue was purified by silica gel column eluted with (PE/Acetone=30/1) to give the title compound (1.45 g, 70% yield) as a white solid.
  • 2
  • [ 2439-54-5 ]
  • [ 175422-04-5 ]
  • [ 871820-11-0 ]
  • 3
  • [ 67-56-1 ]
  • [ 175422-04-5 ]
  • [ 117873-72-0 ]
YieldReaction ConditionsOperation in experiment
Methanol (1.48 g, 46.1 mmol) is slowly added to a cooled suspension (00C) of NaH (2.12 g, 53.2 mmol, 60% dispersion in mineral oil, washed with hexane prior to <n="85"/>use) in THF (20 ml_). Upon completion of the addition the mixture is stirred at 00C for 150 min before 2,6-dibromo-4-nitropyridine (10.0 g, 35.4 mmol) is added. The temperature rises to 14C. The mixture is stirred at rt for 3 h before the reaction is quenched with sat. aq. NH4CI solution. The mixture is diluted with water and extracted twice with EA (250 ml_). The combined org. extracts are dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with DCM to give 2,6-dibromo-4-methoxy-pyridine (6.43 g) as an off-white solid; LC-MS: tR = 0.90 min, [M+1]+ = 267.75.
a) Methanol (1.48 g, 46.1 mmol) is slowly added to a cooled suspension (0 C.) of NaH (2.12 g, 53.2 mmol, 60% dispersion in mineral oil, washed with hexane prior to use) in THF (20 mL). Upon completion of the addition the mixture is stirred at 0 C. for 150 min before 2,6-dibromo-4-nitropyridine (10.0 g, 35.4 mmol) is added. The temperature rises to 14 C. The mixture is stirred at rt for 3 h before the reaction is quenched with sat. aq. NH4Cl solution. The mixture is diluted with water and extracted twice with EA (250 mL). The combined org. extracts are dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with DCM to give 2,6-dibromo-4-methoxy-pyridine (6.43 g) as an off-white solid; LC-MS: tR=0.90 min, [M+1]+=267.75.
  • 4
  • [ 175422-04-5 ]
  • [ 117873-72-0 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; methanol; mineral oil; (1) Production of 2,6-dibromo-4-methoxy pyridine as an intermediate product 1.49 g (ca. 60% in mineral oil; 0.0355*1.05 mol) of sodium hydride was washed with hexane and suspended in tetrahydrofuran. The suspension was mixed with 1.70 g (0.0355*1.5 mol) of methanol and then with 10.00 g (0.0355 mol) of 2,6-dibromo-4-nitropyridine, and stirred at room temperature for about one hour. Further, the suspension was mixed with 0.2 g (ca. 60% in mineral oil; 0.0355*0.14 mol) of sodium hydride, and stirred for about one hour. Next, 1.0 g (0.0355*0.9 mol) of methanol was added to the suspension, and after it was determined that no foaming was caused therein, the reaction solution was distributed with ethyl acetate-saturated sodium bicarbonate water. The organic phase of the obtained reaction solution was washed with saturated brine, dried with anhydrous sodium sulfate and then concentrated, thereby obtaining an aimed product. Yield by weight: 9.27 g; yield by percentage: 98%; solid; melting point: 131 to 133 C.; 1 H-NMR (60 MHz, CDCl3, delta): 3.79 (3H, s), 6.89 (2H, s).
In tetrahydrofuran; methanol; mineral oil; (1) Synthesis of an Intermediate, 2,6-dibromo-4-methoxypyridine Sodium hydride (1.49 g (ca.60% in mineral oil), 0.0355*1.05 mol) was washed with hexane and suspended in tetrahydrofuran, and methanol (1.70 g, 0.0355*1.5 mol) was added thereto. Then, 2,6-dibromo-4-nitropyridine (10.00 g, 0.0355 mol) was added thereto and the resultant solution was stirred for about 1 hour at room temperature. Additional sodium hydride (0.2 g (Ca.60% in mineral oil), 0.0355*0.14 mol) was added, then the resultant solution was stirred for about 1 hour. After it was confirmed that there was no bubbling with the addition of methanol (1.0 g, 0.0355*0.9 mol), the reaction solution was partitioned between ethyl acetate and aqueous saturated sodium hydrogen carbonate. The obtained organic layer was washed with aqueous saturated sodium chloride, dried over anhydrous sodium sutfate and thereafter concentrated to obtain the end product. Yield: 9.27 g (98%). Solid. Melting point: 131 to 133 C. 1 H-NMR (60 MHz, CDCl3, delta): 3.79(3H, s), 6.89(2H, s).
  • 5
  • [ 124-41-4 ]
  • [ 175422-04-5 ]
  • [ 276251-83-3 ]
 

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Technical Information

Categories

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