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Structure of 72521-00-7

Chemical Structure| 72521-00-7

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Product Details of [ 72521-00-7 ]

CAS No. :72521-00-7
Formula : C8H7N3O2
M.W : 177.16
SMILES Code : O=[N+](C1=CC2=C(C=C1C)C=NN2)[O-]
MDL No. :MFCD09026996
InChI Key :AZWAXIMNWVYSMP-UHFFFAOYSA-N
Pubchem ID :12637837

Safety of [ 72521-00-7 ]

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

Computational Chemistry of [ 72521-00-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 9
Fraction Csp3 0.12
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 49.88
TPSA ?

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

74.5 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.84
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.

1.78
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.

1.18
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

0.27
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.16

Water Solubility

Log S (ESOL):?

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

-2.49
Solubility 0.577 mg/ml ; 0.00326 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.

-2.93
Solubility 0.207 mg/ml ; 0.00117 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

-2.68
Solubility 0.373 mg/ml ; 0.0021 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

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.

-6.14 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

2.0 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)

1.77

Application In Synthesis of [ 72521-00-7 ]

* 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 [ 72521-00-7 ]

[ 72521-00-7 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 2124-47-2 ]
  • [ 72521-00-7 ]
  • 2
  • [ 2124-47-2 ]
  • [ 72521-00-7 ]
YieldReaction ConditionsOperation in experiment
58.1% With acetic acid; sodium nitrite; In water; at 0 - 25℃; Preparation 6; 1-[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-5-methyl-1H-indazol-6-ylamineThe synthetic procedure used in this preparation is outlined in Scheme F. Step 1 5-Methyl-6-nitro-1H-indazole<strong>[2124-47-2]2,4-Dimethyl-5-nitroaniline</strong> (1.662 g, 10.00 mmol) was dissolved in glacial acetic acid (100 ml) and the mixture was cooled to 0 C. A solution of sodium nitrite (1 eq, 690 mg) in water (2 ml) was added while maintaining a temperature below 25 C. Stirring was continued for three hours and the mixture was filtered. The filtrate was allowed to stand for three days at room temperature, then was concentrate under reduced pressure. The residue was diluted with water and the resulting mixture was stirred vigorously. The solid product was collected by filtration, washed thoroughly with cold water, and dried. The product was purified by flash chromatography (99:1 dichloromethane/methanol) to give 1.030 g (58.1%) of 5-methyl-6-nitro-1H-indazole as a solid.
58.1% With acetic acid; sodium nitrite; In water; at 0 - 25℃; Step 1 5-Methyl-6-nitro-1H-indazole<strong>[2124-47-2]2,4-Dimethyl-5-nitroaniline</strong> (1.662 g, 10.00 mmol) was dissolved in glacial acetic acid (100 ml) and the mixture was cooled to 0 C. A solution of sodium nitrite (1 eq, 690 mg) in water (2 ml) was added while maintaining a temperature below 25 C. Stirring was continued for three hours and the mixture was filtered. The filtrate was allowed to stand for three days at room temperature, then was concentrate under reduced pressure. The residue was diluted with water and the resulting mixture was stirred vigorously. The solid product was collected by filtration, washed thoroughly with cold water, and dried. The product was purified by flash chromatography (99:1 dichloromethane/methanol) to give 1.030 g (58.1%) of 5-methyl-6-nitro-1H-indazole as a solid.
Example 168; Synthesis of 6-piperazin-l-yl-2-(2-trifluoromethyl-phenylamino)-lH-benzoimidazole-5- carboxylic acid (5-methyl-lH-indazol-6-yl)amideTo a mixture of 2,4-dimethylaniline (10 mmol) in 5 mL of cone. H2SO4, fuming HNO3 (90%; 0.6 mL) was added dropwise at 0 0C. The resulting mixture was stirred for 12 h at RT and then slowly poured into ice. The solid was collected by filtration and dried to yield <strong>[2124-47-2]2,4-dimethyl-5-nitroaniline</strong> as a yellow solid.A solution of nitroaniline (5 mmol) obtained as above in HOAc (5 mL) at RT was added with zso-amyl nitrite (6 mmol) dropwise. The resulting mixture was stirred at RT for 14 h and then slowly poured on to cold saturated aqueous NaHCO3 solution (15 mL). The contents were extracted with ethyl acetate (3 x 20 mL), and the combined organics was washed with 5% aqueous Na2Ctheta3 solution (30 mL). The volatiles were removed in vacuo to give 6-nitro-5-methylindazole as a brown solid.The nitro compound (2 mmol) obtained as above was reduced under hydrogenation conditions as described in general procedure F to afford 6-amino-5-methylindazole as a brown solid. The aminoindazole from above (1.5 mmol) was reacted with 4-chloro-2-fluoro-5- nitrobenzoyl chloride (1.5 mmol) employing the conditions described in Example 115. The product, 2-chloro-4-fluoro-N-(5-methyl-lH-indazol-6-yl)-5-nitrobenzamide, was also isolated similar to Example 115.A solution of the amide from above (1 mmol) in dioxane (2 mL) was reacted with aqueous NH4OH using the conditions described in Example 115. After the formation of 4- <n="92"/>amino-2-chloro-N-(5-methyl-lH-indazol-6-yl)-5-nitrobenzamide was complete, charged with piperazine (5 mmol). The contents were heated at reflux for 1O h and the reaction mixture was cooled to RT. The contents were poured onto ice cold water with vigorous stirring. The solid formed was collected by filtration, washed with water, and dried in vacuo to provide the product, 4-amino-N-(5-methyl-lH-indazol-6-yl)-5-nitro-2-piperazin-l-yl-benzamide as a yellow solid.The product from above (0.6 mol) was treated with BOC anhydride employing the procedure described for Example 163.The nitro aniline from above (0.5 mmol) was reduced under hydrogenation conditions as described in general procedure F to afford 4-[4,5-diamino-2-(5-methyl-lH-mdazol-6- ylcarbamoyl)-phenyl]piperazine-l-carboxylic acid tert-butyl ester.The diamine (0.3 mmol) from above was reacted with l-isothiocyanato-2- trifluoromethylbenzene (0.3 mmol) followed by cyclization in situ using EDC as described in general procedure B to provide 4-[6-(5-Methyl-lH-indazol-6-ylcarbamoyl)-2-(2- trifluoromethyl-phenylamino)-3H-benzoimidazol-5-yl]piperazine-l-carboxylic acid tert-butyl ester. MS: m/z 635 (M+H)+.The product from above was treated with 4M HCl in dioxane employing the procedure described for Example 156 to afford 6-piperazin-l-yl-2-(2-trifluoromethyl- phenylamino)-lH-benzoimidazole-5-carboxylic acid (5-methyl-lH-indazol-6-yl)amide as a hydrochloride salt. MS: m/z 535 (M+H)+.
 

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