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Chemical Structure| 7411-23-6
Chemical Structure| 7411-23-6

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3,5-Dibromo-1H-1,2,4-triazole

CAS No.: 7411-23-6

4.5 *For research use only!

Cat. No.: A153419 Purity: 98%

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Product Citations

Product Citations

Raffael Davenport ; Alice Pru’homme ; Florence Masse , et al.

Abstract: Several synthetic routes toward triazole building block 2-(3-methyl-1H-1,2,4-triazol-1-yl)acetic acid are described. The main problems of the initial synthetic route via alkylation of 3-Me-1H-1,2,4-triazole, such as poor regioselectivity, low yield, and purification by column chromatography, could be significantly improved or completely avoided in the second-generation approaches. Key concepts for the design of the alternative synthesis approaches to solve the problem of regioselectivity were the desymmetrization of 3,5-dibromo-1H-1,2,4-triazole and the de novo synthesis of the triazole core. The scalability of all routes was demonstrated on >100 g scale

Keywords: process ; triazole ; safety ; DABAl-Me3 ; CXCR3 antagonist

Purchased from AmBeed:

Product Details of [ 7411-23-6 ]

CAS No. :7411-23-6
Formula : C2HBr2N3
M.W : 226.86
MDL No. :MFCD00487260
Boiling Point : No data available
InChI Key :FRAKFBWDPXYIQO-UHFFFAOYSA-N
Pubchem ID :81904

Safety of [ 7411-23-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Calculated chemistry of [ 7411-23-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 7
Num. arom. heavy atoms 5
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 31.78
TPSA ?

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

41.57 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.93
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

2.24
Log Po/w (WLOGP)?

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

1.33
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.

0.81
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

2.65
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.59

Water Solubility

Log S (ESOL):?

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

-3.19
Solubility 0.148 mg/ml ; 0.000651 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.

-2.75
Solubility 0.405 mg/ml ; 0.00178 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

-2.58
Solubility 0.604 mg/ml ; 0.00266 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

No
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.

-6.09 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

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)

2.2

Application In Synthesis [ 7411-23-6 ]

* 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 [ 7411-23-6 ]

[ 7411-23-6 ] Synthesis Path-Downstream   1~4

  • 2
  • [ 16427-44-4 ]
  • [ 7411-23-6 ]
  • 3,5-dibromo-1-(2-methoxyethyl)-1,2,4-triazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
58% In a 100 mL round bottomed flask, 3,5-dibromo-1H-1,2,4-triazole (Int-1, 500.0 mg, 2.2 mmol) was dissolved in DMF (32 mL) and the solution was cooled to 0-5 C (ice bath). Sodium hydride (55% dispersion in mineral oil, 106 mg, 2.64 mmol) was added in portions and the resulting mixture was stirred for 5 min at 0-5 C and for 15 min at room temperature. After that, <strong>[16427-44-4]2-methoxyethyl methanesulfonate</strong> (815.5 mg, 5.29 mmol) was added dropwise at room temperature. The resulting mixture was stirred for 15 h at room temperature. After that, it was diluted with ethyl acetate (20 mL) and water (20 mL), the aqueous phase was extracted with ethyl acetate (3 x 30 mL). The combined organic layers were dried (sodium sulfate) and concentrated in vacuo, the residue was purified by column chromatography (silica gel, 30 g, eluting with ethyl acetate / n-heptane, gradient 0: 100 to 20:80 v/v) to yield the title compound as colorless oil (362 mg, 58%). 1H NMR (CDC13, 300 MHz): 3.33 (s, 3 H), 3.76 (t, J = 5.3 Hz, 2 H), 4.29 (t, J = 5.3 Hz, 2 H). MS (ES+) m/z 285.8.
  • 3
  • [ 78385-26-9 ]
  • [ 7411-23-6 ]
  • 3,5-dibromo-1-[(3-methyloxetan-3-yl)methyl]-1,2,4-triazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
98.5% In a 250 mL round bottomed flask sodium hydride (60% dispersion in mineral oil) (264 mg, 6.61 mmol) was added to a colorless solution of 3,5-dibromo-1H-1,2,4-triazole (Int-1, 1 g, 4.41 mmol) in DMF (22 ml). The resulting suspension was stirred at room temp during 30 min and <strong>[78385-26-9]3-(bromomethyl)-3-methyloxetane</strong> (873 mg, 5.29 mmol) was added and the reaction was stirred at 40C over night.The reaction mixture was poured into 50 mL H20 and extracted with EtOAc (3 x 50 mL). The organic layers were washed with sat NaCl (3 x 50 mL), dried over MgS04 and concentrated in vacuo. The title compound was isolated as a colorless liquid (1.35 g, 98.5 % yield). MS (ES+) m/z: 311.9 [(M+H)+].
  • 4
  • [ 121138-01-0 ]
  • [ 7411-23-6 ]
  • 3,5-dibromo-1-(oxolan-3-yl)-1,2,4-triazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
94.6% With potassium carbonate; In N,N-dimethyl-formamide; at 120℃;Sealed tube; Inert atmosphere; To a colorless solution of 3,5-dibromo-1H-1,2,4-triazole (lnt-1, 500 mg, 2.2 mmol) and <strong>[121138-01-0]3-iodotetrahydrofuran</strong> (524 mg, 2.64 mmol) in DMF (3 ml) was added K2C03 (305 mg, 2.2 mmol). The vial was closed under Argon and stirred over night at 120C. The reaction mixture was diluted with 50 mL H20 and extracted with EtOAc (2 x 50 mL). The organic layers were washed with sat NaCl (3 x 50 mL), dried over MgS04 and concentrated in vacuo. The title compound was isolated as a white solid (619 mg, 2.08 mmol, 94.6 % yield). MS (ES+) m/z 297.9 [(M+H)+].
 

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