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Chemical Structure| 766-55-2 Chemical Structure| 766-55-2

Structure of 766-55-2

Chemical Structure| 766-55-2

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Product Details of [ 766-55-2 ]

CAS No. :766-55-2
Formula : C6H5N3
M.W : 119.12
SMILES Code : C1=CN=C2C=CC=N[N]12
MDL No. :MFCD07782103
InChI Key :VTVRXITWWZGKHV-UHFFFAOYSA-N
Pubchem ID :136599

Safety of [ 766-55-2 ]

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

Computational Chemistry of [ 766-55-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 9
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 32.99
TPSA ?

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

30.19 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.35
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

0.33
Log Po/w (WLOGP)?

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

0.73
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.

0.56
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

0.58
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.71

Water Solubility

Log S (ESOL):?

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

-1.53
Solubility 3.54 mg/ml ; 0.0298 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-0.53
Solubility 35.3 mg/ml ; 0.297 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very 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

-1.66
Solubility 2.59 mg/ml ; 0.0218 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.

-6.79 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)

1.69

Application In Synthesis of [ 766-55-2 ]

* 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 [ 766-55-2 ]

[ 766-55-2 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 766-55-2 ]
  • [ 18087-73-5 ]
YieldReaction ConditionsOperation in experiment
89% With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); at 40 - 45℃; 2) Add 2g of azobisisobutyronitrile to the reaction solution in the previous step, and add NBS 187g in batches. Pay attention to avoid light reaction. After the addition, control the temperature at 40 ~ 45 C and stir for 5 ~ 6 hours. The prepared 10% sodium bisulfite solution was added to the reaction bottle and stirred for 30 minutes (crack the excess NBS), and the temperature was reduced to -5C with suction to obtain a brown solid.Product II product 176g, yield 89%,The mother liquor can be recovered and applied after being layered.
75% With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In chloroform; for 2h;Reflux; The imidazo [1,2-b] pyridazine (6.0g, 50 . 4mmol), NBS (6.0g, 75 . 6mmol) and a catalytic amount of AIBN is added to the 50 ml chloroform, heating to reflux the reaction 2 hours, TLC detection of the reaction process, the raw materials of the reaction after cooling to room temperature stirring under the conditions of the ice bath, a precipitate out, filtered and the filtrate concentrated to get the pure product.The pure product as a pale yellow solid, yield: 75%
75% With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In chloroform; for 2h;Reflux; The imidazo [1,2-b] pyridazine (6.0 g, 50.4 mmol), NBS (6.0 g, 75.6 mmol) and a catalytic amount of AIBN were added to 50 mL of chloroform and the reaction was heated to reflux for 2 hours, The reaction solution was cooled to room temperature when the raw material disappeared with the TLC detection of the reaction process, and a precipitate precipitated after the solution stirred in an ice bath. After filtering, the filtrate concentrated under reduced pressure to give the pure product. A pale yellow solid, yield: 75%. 1H NMR (CDCl3, 400 MHz, delta ppm): 8.50 (d, J = 3.6 Hz, 1H), 8.01-7.98 (m, 1H), 7.84 (s, 1H), 7.15-7.12 (m, 1H). ESI-MS m/z : 200.1 [M+H]+.
74% With N-Bromosuccinimide; In chloroform; for 0.5h;Reflux; Example 15 -4 Synthesis of 3-bromo-imidazo[1,2-b]pyridazine To imidazo[1,2-b]pyridazine 1*b (10 g) stirring in chloroform (250 ml) was added N-bromosuccinimide (15.7 g) at 5 C. The cooling bath was removed and the reaction was heated to reflux which was maintained for 30 minutes. After leaving to cool overnight the reaction mixture was concentrated under reduced pressure. The residue was redissolved in ethyl acetate (500 ml), washed with potassium carbonate solution (3 x 200 ml) then brine (100 ml). The organic extract was dried with magnesium sulphate and concentrated in vacuo to give 3-bromo-imidazo[1,2-b]pyridazine 2*b, 12.3 g (74%). 1H-NMR (400MHz, DMSO-D6) : delta = 8.68 (1 H, d, 4.4 Hz, ArH), 8.20 (1 H, d, 9.2 Hz, ArH), 7.95 (1 H, s, ArH), 7.33 (1 H, q, 3.4 Hz, ArH).
36% With bromine; acetic acid; at 0 - 20℃; for 1h; To a stirred solution of imidazo[1,2-bjpyridazine (200 mg, 1.679 mmol) in acetic acid (10 mL) was added bromine (0.2 mL, 3.88 mmol) at 0 C. The reaction mixture was allowed to warm to room temperature and stir for 1 hr. The reaction mixture was neutralized with iN sodium hydroxide, poured into EtOAc (20 mL) and 10% NaHCO3 solution. The layers were separated and the aqueous layer extracted with EtOAC (3x20ml). The combined organic layer was washed with brine, dried over Na2SO4, and concentrated to give 3-bromoimidazo[1,2-bjpyridazine (120 mg, 36%) as light brown solid. ?H NMR (400 MHz, DMSO-d6) oe 8.68 (dd, J=4.52, 1.51 Hz, 1 H) 8.19 (dd, J=9.54, 1.51 Hz, 1 H) 7.94 (s, 1 H) 7.28-7.39 (m, 1 H).
With bromine; In acetic acid; at 20℃; EXAMPLE 1; Lambda/-[(l,6i?)-6-Amino-2,2-difluorocyclohexyl]-4-(imidazo[1,2-b]pyridazin-3-yl)-5- methylthiophene-2-carboxamide; 3 -Bromoimidazo [ 1,2-b]pyridazine; Bromine (0.649 mL, 12,6 mmol) was added dropwise to a stirred mixture of Imidazo[1,2- 6]pyridazine (1.0 g, 839 mmol) in acetic acid (42 ml) and the mixture was stirred at room temperature for 1 h. The mixture was neutralized with 1 N sodium hydroxide (100 mL) and solid sodium hydroxide, poured into ethyl acetate and sodium bicarbonate solution, and extracted with ethyl acetate (3 x 200 mL). The combined organics were washed with brine, dried (MgSO,*), and concentrated to afford the title compound. 1H NMR (600 MHz, CD3SOCD3) delta 8.66 (d, 1H); 8.17 (d, 1H); 7.93 (s, 1H); 7.31 (dd, 1H). LRMS (APCI) calc'd for (C6H5BrN3) [M+H]+, 198.0; found 198.0.
With N-Bromosuccinimide; In chloroform; for 2h;Reflux; A mixture of imidazo[1,2-b]pyridazine (2.0 g), N-bromosuccinimide (2.94 g), and chloroform (100 mL) was heated under reflux for 2 hr. Upon cooling, the solution was treated with a saturated aqueous solution of sodium carbonate (200 mL) and shaken. The chloroform layer was separated and concentrated to afford the compound 3-bromoimidazo[1,2-b]pyridazine (IIb).
9.9 g With N-Bromosuccinimide; In chloroform; for 0.5h;Reflux; theImidazo [1,2-b] pyridazin(50mmol) dissolved in Chloroform (50 ml), Bromosuccinimide(55 mmoles) was slowly added into the reaction . at reflux System was stirredfor 30 minutes. After cooling to room temperature, the pH was adjusted to 8-9 usingsaturated aqueous sodium carbonatesolution and extracted with ethyl acetate. The extract was washed with water andsaturated brine. After dried overanhydrous sodium sulfate and concentrated to give 9.9 g of the title compound.
9.9 g With N-Bromosuccinimide; In chloroform; for 0.5h;Reflux; The imidazo [l, 2_b] pyridazine ¢ .0 g, 50 mmol) was dissolved in chloroform (50 ml), N- bromobutyrate ni imide (NBS) (9.8 g, 55 mmol mol) was slowly added thereto.Was refluxed for 30 minutes.After cooling to room temperature, the PH value was adjusted to 8-9 with saturated sodium carbonate solution, extracted with ethyl acetate.The extract was washed with water, brine, dried over anhydrous sodium sulfate, and concentrated to give the title compound 9.9 g.
With N-Bromosuccinimide; In ethyl acetate; at 95℃; for 2h; Was added 3-amino-pyridazine in 250 ml single neck round bottom flask (9.51g, 100mmol), 40% aqueous solution of chloroacetaldehyde (chloroacetaldehyde 190mmol) and 81g of ethyl acetate, Start the magnetic stirrer, the mixture of the reaction flask The reaction was stirred at 85 C for 2 hours. TLC, starting material 3-amino-pyridazine completion of the reaction, was added N- bromosuccinimide (17.80g, 100mmol), 95 under stirring for 2 hours,TLC and GC detection to determine the intermediate imidazo [1,2-b] pyridazine was complete. The reaction mixture was suction filtered, the reaction solution was suction filtered, the filter cake with ethyl acetate: n-hexane = 1: 5 to give the pure product recrystallized from 3-bromo-imidazo [1,2-b] pyridazine, the filtrate with ethyl acetate. The pure product was obtained by recrystallization from ethyl acetate: n-hexane = 1: 5 to give the pure product 3-bromoimidazo [1,2-b] pyridazine. After drying, the yield was calculated 88.98%, purity 99% (HPLC).

 

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