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Chemical Structure| 56434-28-7 Chemical Structure| 56434-28-7

Structure of 56434-28-7

Chemical Structure| 56434-28-7

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Product Details of [ 56434-28-7 ]

CAS No. :56434-28-7
Formula : C6H6N2O3
M.W : 154.12
SMILES Code : COC1=CC=C(N=N1)C(O)=O
MDL No. :MFCD09800587
InChI Key :SMBBNQVBFDIQMJ-UHFFFAOYSA-N
Pubchem ID :12214461

Safety of [ 56434-28-7 ]

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

Computational Chemistry of [ 56434-28-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.17
Num. rotatable bonds 2
Num. H-bond acceptors 5.0
Num. H-bond donors 1.0
Molar Refractivity 35.48
TPSA ?

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

72.31 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.83
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

0.01
Log Po/w (WLOGP)?

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

0.18
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.

-0.22
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

0.26
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.21

Water Solubility

Log S (ESOL):?

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

-1.07
Solubility 13.0 mg/ml ; 0.0844 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.

-1.08
Solubility 12.8 mg/ml ; 0.0832 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

-1.14
Solubility 11.2 mg/ml ; 0.0728 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

No
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.

-7.23 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.

0.56

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)

2.01

Application In Synthesis of [ 56434-28-7 ]

* 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 [ 56434-28-7 ]

[ 56434-28-7 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 124-41-4 ]
  • [ 65202-50-8 ]
  • [ 56434-28-7 ]
YieldReaction ConditionsOperation in experiment
29.0 g In methanol;Inert atmosphere; Reflux; In a nitrogen atmosphere, a mixture of <strong>[65202-50-8]methyl 6-chloropyridazine-3-carboxylate</strong> (40 g), sodium methoxide (62.5g) and methanol (600 mL) was heated to reflux overnight. The reaction mixture was cooled to room temperature.Hydrochloric acid was added to the reaction mixture at 0°C to adjust the pH to 3. The solvent was distilled off, and then,the residue was dissolved in water (200 mL), followed by extraction with ethyl acetate (300 mL) three times. The combinedorganic layer was washed with saturated brine, then dried over sodium sulfate and concentrated. The residue waswashed with methyl t-butyl ether/petroleum ether (1:5) to obtain 6-methoxypyridazine-3-carboxylic acid (29.0 g). A mixtureof 6-methoxypyridazine-3-carboxylic acid (29.0 g), sulfuric acid (2 mL) and methanol (500 mL) was stirred at roomtemperature for 3 days. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture to adjustthe pH to 7. The solvent was distilled off, and then, the residue was dissolved in water (200 mL), followed by extractionwith ethyl acetate (200 mL) three times. The combined organic layer was washed with saturated brine, then dried oversodium sulfate and concentrated. The obtained residue was purified by column chromatography (ethyl acetate/petroleumether) to obtain methyl 6-methoxypyridazine-3-carboxylate (22.0 g). A mixture of methyl 6-methoxypyridazine-3-carboxylate(4.5 g), hydrazine hydrate (80percent, 13.4 g) and methanol (50 mL) was stirred overnight at room temperature. Water(10 mL) was added to the reaction mixture, and the mixture was concentrated. Methanol was distilled off from the mixture,and the residue was freeze-dried. The residue was washed with petroleum ether to obtain 6-methoxypyridazine-3-carbohydrazide (4.2 g). 2-Chloro-2-oxoethyl acetate (16.3 g) was added dropwise to a mixture of 6-methoxypyridazine-3-carbohydrazide (20 g), dichloromethane (250 mL) and water (10 mL) at 0°C. The mixture was stirred at 0°C for 30minutes and then stirred at room temperature for 1.5 hours. The reaction mixture was concentrated under reducedpressure. Water (20 mL) was added to the obtained residue, and the mixture was freeze-dried. The residue was washedwith petroleum ether to obtain 2-(2-((6-methoxypyridazin-3-yl)carbonyl)hydrazino)-2-oxoethyl acetate (25.0 g). A mixtureof 2-(2-((6-methoxypyridazin-3-yl)carbonyl)hydrazino)-2-oxoethyl acetate (25.0 g), diphosphorus pentasulfide (21.4 g)and THF (600 mL) was stirred overnight at 50°C. The reaction mixture was cooled to room temperature, and the reactionwas terminated by the addition of a saturated aqueous solution of sodium bicarbonate. The mixture was subjected toextraction with ethyl acetate (500 mL) three times. The combined organic layer was washed with saturated brine, thendried over sodium sulfate and concentrated. The obtained residue was purified by column chromatography (dichloromethane/methanol) to obtain (5-(6-hydroxypyridazin-3-yl)-1,3,4-thiadiazol-2-yl)methyl acetate (7.9 g). Amixture of(5-(6-hydroxypyridazin-3-yl)-1,3,4-thiadiazol-2-yl)methyl acetate (7.9 g), phosphoryl chloride (9.6 g) and acetonitrile (200 mL) was stirred at 70°C for 2 hours. The reaction mixture was cooled to room temperature. The reaction was terminatedby the addition of water under ice cooling, and the mixture was subjected to extraction with ethyl acetate (200 mL) threetimes. The combined organic layer was washed with saturated brine, then dried over sodium sulfate and concentrated.The obtained residue was purified by column chromatography (ethyl acetate/petroleum ether) to obtain (5-(6-chloropyridazin-3-yl)-1,3,4-thiadiazol-2-yl)methyl acetate (2.9 g). To a mixture of (5-(6-chloropyridazin-3-yl)-1,3,4-thiadiazol-2-yl)methyl acetate (1.6 g) and THF (50 mL), lithium hydroxide (1 M aqueous solution, 14.8 mL) was added at 0°C. Themixture was stirred at 0°C for 1 hour and then stirred at room temperature for 1 hour. The solvent was distilled off, andthen, the residue was subjected to extraction with ethyl acetate (50 mL) three times. The combined organic layer waswashed with saturated brine, then dried over sodium sulfate and concentrated. The obtained residue was recrystallizedfrom dichloromethane-methanol to obtain (5-(6-chloropyridazin-3-yl)-1,3,4-thiadiazol-2-yl)methanol (1.16 g). A mixtureof 4-(4-(pentafluorosulfanyl)phenyl)-4-(trifluoromethyl)piperidine hydrochloride (200 mg), (5-(6-chloropyridazin-3-yl)-1,3,4-thiadiazol-2-yl)methanol (100 mg), DIPEA (0.650 mL) and IPA (4 mL) was stirred at 150°C for 1 hour underirradiation with microwave. The reaction mixture was concentrated under reduced pressure. The obtained residue waspurified by column chromatography (ethyl acetate/hexane) to obtain the title compound (120 mg).
 

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