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Chemical Structure| 885520-26-3

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4,6-Difluoro-1H-indazole

CAS No.: 885520-26-3

4.5 *For Research Use Only !

Cat. No.: A106269 Purity: 98%

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Product Details of [ 885520-26-3 ]

CAS No. :885520-26-3
Formula : C7H4F2N2
M.W : 154.12
SMILES Code : FC1=CC2=C(C(F)=C1)C=NN2
MDL No. :MFCD07781445
InChI Key :IVIBUEIPYSZJAI-UHFFFAOYSA-N
Pubchem ID :24728423

Safety of [ 885520-26-3 ]

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

Calculated chemistry of [ 885520-26-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 9
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 36.01
TPSA ?

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

28.68 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.12
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

1.75
Log Po/w (WLOGP)?

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

2.68
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.

1.99
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

2.87
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.08

Water Solubility

Log S (ESOL):?

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

-2.5
Solubility 0.483 mg/ml ; 0.00314 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.

-1.97
Solubility 1.65 mg/ml ; 0.0107 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

-3.45
Solubility 0.0543 mg/ml ; 0.000352 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.

-6.0 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)

1.64

Application In Synthesis [ 885520-26-3 ]

* 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 [ 885520-26-3 ]

[ 885520-26-3 ] Synthesis Path-Downstream   1~9

  • 1
  • [ 885520-26-3 ]
  • [ 1426417-11-9 ]
  • 2
  • [ 885520-26-3 ]
  • [ 887567-79-5 ]
YieldReaction ConditionsOperation in experiment
2.18 g With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 2h; Example 101.2-(4,6-Difiuoro-l-methyl-lH-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylisopropylamideStep 14 ,6 -Difluoro -3 -iodo - 1 H-indazo leTo a solution of 4,6-difluoro-l H-indazo le (1.16 g, 7.53 mmol) in DMF (60 ml) at room temperature was added potassium hydroxide ( 1.27 g, 22.6 mmol) and iodine (2.87 g, 11.3 mmol). The maroon reaction mixture was stirred at room temperature for 2 h then quenched with 10% aqueous Na2S203 and diluted with water. The mixture was extracted with EtOAc (2x). The combined organics were washed with water, sat LiCl, and sat NaCl, then dried over MgSC^ and concentrated to afford 2.18 g of 4,6-difluoro-3-iodo-l H-indazo le as a light brown solid.
  • 3
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  • [ 1426422-22-1 ]
  • 4
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  • [ 1426422-23-2 ]
  • 5
  • [ 885520-26-3 ]
  • [ 1426422-24-3 ]
  • 6
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  • [ 1426422-25-4 ]
  • 7
  • [ 885520-26-3 ]
  • [ 1426422-26-5 ]
  • 8
  • [ 58551-83-0 ]
  • [ 885520-26-3 ]
YieldReaction ConditionsOperation in experiment
47% Example 88.2-(4,6-Difluoro-l-methyl-lH-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2- (3-cyano-azetidin-l -yl)-l -methyl-2-oxo-ethyl]-amideStep 14,6-Difluoro-lH-indazoleTo a solution of 2,4,6-trifluorobenzaldehyde (0.80 g, 5.0 mmol) in 1 ,2-dimethoxyethane (10 mL) were added potassium carbonate (1.04 g, 7.5 mmol) and O-methylhydroxylamine hydrochloride (438 mg, 5.25 mmol). The reaction mixture was heated at 50C for 5 h then cooled to room temperature and filtered, rinsing with dichloromethane. The filtrate was concentrated. The residue was dissolved in 1 ,2-dimethoxyethane (10 mL) and hydrazine (0.17 mL, 5.5 mmol) was added. The reaction mixture was heated at 100C for 1.5 h. Additional hydrazine (0.17 mL, 5.5 mmol) was added and heating was continued for 30 min. Thereaction was cooled to room temperature, poured into water, and extracted with ethyl acetate. The organic layer was washed with sat LiCl and brine then dried over MgS04 and concentrated. The residue was purified by silica gel chromatography with 20% to 50% EtO Ac/heptane to provide 358 mg (47%) of 4,6- difluoro- lH-indazole as a light yellow solid. 1H NMR (DMSO-d6, 300 MHz): ? (ppm) 13.47 (br. s., 1H), 8.19 (s, 1H), 7.22 (d, J=9.1 Hz, 1H), 6.96 (td, J=10.0, 1.9 Hz, 1H).
  • 9
  • (rac)-methyl (2S,3S)-3-[(2-chloro-5-fluoro-pyrimidin-4-yl)amino]bicyclo[2.2.2]octane-2-carboxylate [ No CAS ]
  • [ 885520-26-3 ]
  • (2S,3S)-methyl-3-((2-(4,6-difluoro-1H-indazol-1-yl)-5-fluoropyrimidin-4-yl)amino)bicyclo[2.2.2]octane-2-carboxylate [ No CAS ]
 

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