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Structure of 58633-04-8

Chemical Structure| 58633-04-8

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Product Details of [ 58633-04-8 ]

CAS No. :58633-04-8
Formula : C7H4Br2N2
M.W : 275.93
SMILES Code : N#CC1=CC(Br)=C(N)C(Br)=C1
MDL No. :MFCD03094688
InChI Key :UWIGJWZPRNWPBK-UHFFFAOYSA-N
Pubchem ID :2735314

Safety of [ 58633-04-8 ]

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

Computational Chemistry of [ 58633-04-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
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 50.96
TPSA ?

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

49.81 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.94
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

2.34
Log Po/w (WLOGP)?

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

2.67
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.

2.28
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

2.44
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.33

Water Solubility

Log S (ESOL):?

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

-3.43
Solubility 0.103 mg/ml ; 0.000373 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.

-3.03
Solubility 0.26 mg/ml ; 0.000943 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

-3.83
Solubility 0.0411 mg/ml ; 0.000149 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

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.

-6.32 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)

1.88

Application In Synthesis of [ 58633-04-8 ]

* 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.

  • Upstream synthesis route of [ 58633-04-8 ]

[ 58633-04-8 ] Synthesis Path-Upstream   1~2

  • 1
  • [ 873-74-5 ]
  • [ 58633-04-8 ]
YieldReaction ConditionsOperation in experiment
87% With 1,2-diphenyl-1,1,2,2-tetrahydroperoxyethane; hydrogen bromide In water; acetonitrile at 20℃; for 2.5 h; General procedure: To a solution of aniline/phenol (1 mmol) in CH3CN (4 mL), HBr and THPDPE (depending on the substrate as shown in Table 7) were added and the solution was stirred at room temperature. After the reaction was completed, Na2SO3 (3M, 1mL) was added to the stirring mixture followed by the addition of H2O (10 mL). The solution was stirred until the desired precipitates appeared. The products were filtered and more purification was carried out using silica- packed column chromatography (Hexane–EtOAc). All of the products were characterized on the basis of their melting points, IR, 1H NMR, and 13C NMR spectral analysis and compared with those reported
74% With bromine In 1,4-dioxane; sodium hydroxide EXAMPLE 25
PREPARATION OF 4-AMINO-3,5-DIBROMOBENZONITRILE STR37
To a stirred solution of 100 mg (0.847 mmoles) of p-aminobenzonitrile in 3.6 mL dioxane chilled in an ice-bath was added sequentially 356 μL (1.78 moles) of 5N sodium hydroxide solution and mg (1.78 mmoles) of bromine.
The ice-water bath was removed and the reaction mixture was stirred further for 1.5 hours.
After this time, 21.8 μL (0.423 mmoles) of bromine was added to drive the reaction to completion and stirring was continued for 10 minutes.
The mixture was partitioned between ethyl acetate and ice-water and the organic phase was separated.
It was washed with brine, dried over anhydrous sodium sulfate, filtered, and evaporated.
Purification by plate layer chromatography using hexane-ethyl acetate (7:3) as the eluant provided 175 mg (74percent) of the entitled product.
NMR(CDCl3) δ5.1 (bs, 2H), 7.66 (s, 2H).
References: [1] RSC Advances, 2016, vol. 6, # 93, p. 90184 - 90187.
[2] Journal fuer Praktische Chemie (Leipzig), 1986, vol. 328, # 4, p. 497 - 514.
[3] Tetrahedron, 2018, vol. 74, # 45, p. 6584 - 6592.
[4] Journal of Organic Chemistry, 1998, vol. 63, # 5, p. 1555 - 1565.
[5] Journal of the American Chemical Society, 1960, vol. 82, p. 3454 - 3456.
[6] Synthesis (Germany), 2013, vol. 45, # 11, p. 1497 - 1504.
[7] Patent: US5455239, 1995, A, .
  • 2
  • [ 873-74-5 ]
  • [ 58633-04-8 ]
YieldReaction ConditionsOperation in experiment
74% With bromine In 1,4-dioxane; sodium hydroxide EXAMPLE 1
Preparation of 4-Amino-3,5-dibromobenzonitrile STR15
To a stirred solution of 100 mg (0.847 mmoles) of p-aminobenzonitrile in 3.6 mL dioxane chilled in an ice-bath was added sequentially 356 μL (1.78 mmoles) of 5 N sodium hydroxide solution and 284 mg (1.78 mmoles) of bromine.
The ice-water bath was removed and the reaction mixture was stirred further for 1.5 hours.
After this time, 21.8 μL (0.423 mmoles) of bromine was added to drive the reaction to completion and stirring was continued for 10 minutes.
The mixture was partitioned between ethyl acetate and ice-water and the organic phase was separated.
It was washed with brine, dried over anhydrous sodium sulfate, filtered, and evaporated.
Purification by plate layer chromatography using hexane-ethyl acetate (7:3) as eluant provided 175 mg (74percent) of the entitled product.
NMR(CDCl3) δ: 5.1 (bs, 2H), 7.66 (s, 2H).
References: [1] Patent: US5192758, 1993, A, .
 

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