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Chemical Structure| 17973-86-3 Chemical Structure| 17973-86-3

Structure of 3,6-Dibromopyridazine
CAS No.: 17973-86-3

Chemical Structure| 17973-86-3

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Product Details of [ 17973-86-3 ]

CAS No. :17973-86-3
Formula : C4H2Br2N2
M.W : 237.88
SMILES Code : C1=CC(=NN=C1Br)Br
MDL No. :MFCD00233947
InChI Key :VQAFMTSSCUETHA-UHFFFAOYSA-N
Pubchem ID :248852

Safety of [ 17973-86-3 ]

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

Computational Chemistry of [ 17973-86-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 37.43
TPSA ?

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

25.78 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.91
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

1.89
Log Po/w (WLOGP)?

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

2.0
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.

1.57
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

2.42
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.96

Water Solubility

Log S (ESOL):?

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

-3.06
Solubility 0.207 mg/ml ; 0.00087 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.

-2.05
Solubility 2.1 mg/ml ; 0.00883 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

-3.36
Solubility 0.103 mg/ml ; 0.000434 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.

-6.41 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)

2.03

Application In Synthesis of [ 17973-86-3 ]

* 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 [ 17973-86-3 ]

[ 17973-86-3 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 17973-86-3 ]
  • [ 151169-74-3 ]
  • 3-bromo-6-(2,3-dichlorophenyl)pyridazine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In monoethylene glycol diethyl ether; water; at 80℃; for 17h; Intermediate 2: 3-Bromo-6-(2,3-dichlorophenyl)pyridazine.To a suspension of 3,6-dibromopyridazine (5g, 21mmol) in ethylene glycol dimethyl ether (100ml) was added 2,3-dichlorophenyl boronic acid (4.03g, 21mmol), tetrakis(triphenylphosphine)palladium(0) (1.2g, 1.05mmol) and sodium carbonate (2N, aqueous) (50ml), the mixture was then heated to 800C for 17 hours whilst under argon. The dark crude reaction mixture was then evaporated to dryness. The residue was partitioned between water (200ml) and dichloromethane (300ml). The aqueous layer was separated and further extracted with dichloromethane (200ml). The combined dichloromethane layers were evaporated and the residue was purified by chromatography (90g of silica) eluting with 75% dichloromethane/ petroleum ether 40:60. The title compound was obtained as a pink coloured solid (680mg). 1H-NMR (CDCl3) ? 7.38 (IH, X, J= 8), 7.58-7.63 (2H, m), 7.70-7.76 (2H, m) LC/MS m/z [MH+] 305 consistent with molecular formula C10H581Br35Cl2N2
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 80℃; for 17h; To a suspension of 3,6-dibromopyridazine (5g, 21mmol) in ethylene glycol dimethyl ether (100ml) was added 2,3-dichlorophenyl boronic acid (4.03g, 21mmol), tetrakis(triphenylphosphine)palladium(0) (1.2g, 1.05mmol) and sodium carbonate (2N, aqueous) (50ml), the mixture was then heated to 800C for 17 hours whilst under argon. The dark crude <n="169"/>reaction mixture was then evaporated to dryness. The residue was partitioned between water (200ml) and dichloromethane (300ml). The aqueous layer was separated and further extracted with dichloromethane (200ml). The combined dichloromethane layers were evaporated and the residue was purified by chromatography (9Og of silica) eluting with 75% dichloromethane/ petroleum ether 40:60. The title compound was obtained as a pink coloured solid (680mg). 1H-NMR (CDCl3) δ 7.38 (IH, t, /= 8), 7.58-7.63 (2H, m), 7.70-7.76 (2H, m) LC/MS m/z [MH+] 305 consistent with molecular formula Ci0H581Br35Cl2N2
  • 2
  • [ 17973-86-3 ]
  • [ 50595-15-8 ]
  • [ 1036226-89-7 ]
YieldReaction ConditionsOperation in experiment
277. 8 mg (2.1 mmol) of hydroxyacetic acid tert-butyl ester and 100.9 mg of sodium hydride (55 percent in mineral oil) in 15 ml of DMF were stirred at room temperature for 30 min. Then 500 mg (2.1 mmol) of 3,6-dibrompyridazine were added, and the reaction mixture was stirred at 60 °C for 2 h. After evaporation to dryness, the residue was stirred with ethyl acetate, the solution filtered, evaporated, and the crude product (450 mg) directly employed in the subsequent step.
  • 3
  • [ 17973-86-3 ]
  • [ 197223-39-5 ]
  • C18H23BrN2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
61.2% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 120℃; for 12h;Inert atmosphere; 1) Weigh 0.05 mol of 3,6-dibromopyridazine in a 250 ml three-vial bottle.0.12 mol of <strong>[197223-39-5](3,5-di-tert-butylphenyl)boronic acid</strong> and 100 ml of toluene were stirred and dissolved, and under the protection of nitrogen, 0.0025 mol of Pd(PPh3)4 and 0.1 mol of potassium carbonate were added.50ml water and ethanol volume ratio of 1:1 mixed solution, stirring heated to 120 ° C, refluxing reaction for 12 hours, sampling point board, significantShows no 3,6-dibromopyridazine remaining, the reaction is complete; naturally cooled to room temperature, filtered, the filtrate layered, the organic phase was taken for vacuumDistilled to zero fractions, over neutral silica gel column to give Intermediate 3-1, HPLC purity 99.3percent, yield 61.2percent;
  • 4
  • [ 280-13-7 ]
  • [ 17973-86-3 ]
  • C10H12BrN3O [ No CAS ]
YieldReaction ConditionsOperation in experiment
67% With triethylamine; In acetonitrile; at 160℃; for 1.66667h;Microwave irradiation; 3,6-Dibromopyridazine (0.2 g, 0.841 mmol) was dissolved in acetonitrile (2.5 ml_). Then 8-oxa-3- azabicyclo[3.2.1]octane (0.105 g, 0.925 mmol) and triethylamine (0.176 ml_, 1.261 mmol) were added and the suspension was irradiated in the microwave to 160C for 1 h and 20 minutes. The reaction mixture was diluted with dichloromethane and water. The organic layer was separated and the aqueous layer was extracted with dichloromethane twice. The combined organic layers were dried over Na2S04, filtered and concentrated under reduced pressure. The crude product was purified on a silica gel column using a Biotage Isolera One purification system employing an n-heptane/ethyl acetate gradient (100/0 -> 0/100) to afford the title compound as a beige solid (0.152 g, 67 %). (0609) MS: 271.5 (M+H)+. (0610) 1H-NMR (400 MHz, Chloroform-d) d = 7.32 (d, J = 9.5 Hz, 1 H), 6.70 (d, J = 9.5 Hz, 1 H), 4.60 - 4.43 (m, 2H), 3.83 (d, J = 12.8 Hz, 2H), 3.23 (dd, J = 12.4, 2.7 Hz, 2H), 2.08 - 1.94 (m, 2H), 1.90 - 1.76 (m, 2H).
 

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Technical Information

Categories

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