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Structure of 33225-72-8

Chemical Structure| 33225-72-8

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Product Details of [ 33225-72-8 ]

CAS No. :33225-72-8
Formula : C6H4N2O4
M.W : 168.11
SMILES Code : O=C(O)C1=C([N+]([O-])=O)N=CC=C1
MDL No. :MFCD04114130
InChI Key :RIMQELJEDBHDQZ-UHFFFAOYSA-N
Pubchem ID :298627

Safety of [ 33225-72-8 ]

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

Computational Chemistry of [ 33225-72-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 2
Num. H-bond acceptors 5.0
Num. H-bond donors 1.0
Molar Refractivity 40.02
TPSA ?

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

96.01 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.27
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

0.54
Log Po/w (WLOGP)?

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

0.69
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.

-1.35
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

-1.37
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.24

Water Solubility

Log S (ESOL):?

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

-1.46
Solubility 5.82 mg/ml ; 0.0346 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.

-2.13
Solubility 1.25 mg/ml ; 0.00745 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

-0.77
Solubility 28.4 mg/ml ; 0.169 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.

-6.94 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

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)

1.87

Application In Synthesis of [ 33225-72-8 ]

* 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 [ 33225-72-8 ]

[ 33225-72-8 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 18368-73-5 ]
  • [ 33225-72-8 ]
  • 4
  • [ 33225-72-8 ]
  • (R)-6-chloro-4-fluoroindan-1-ylamine hydrochloride [ No CAS ]
  • [ 128798-39-0 ]
  • [ 100-52-7 ]
  • 2-nitro-N-[(R)-carbamoylphenylmethyl]-N-[(R)-6-chloro-4-fluoroindan-1-yl]nicotinamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
0.09 g Example 13 2-Amino-N-[(R)-carbamoylphenylmethyl]-N-[(R)-6-chloro-4-fluoroindan-1-yl]nicotinamide To a solution of (R)-6-chloro-4-fluoroindan-1-ylamine hydrochloride (0.1 g) in methanol (3 mL) were added triethylamine (0.046 g) and benzaldehyde (0.048 g), and the mixture was stirred for 0.5 hours at 65° C. The reaction mixture was allowed to cool to room temperature, and to the mixture were added <strong>[33225-72-8]2-nitronicotinic acid</strong> (0.083 g) and 4-phenylcyclohexen-1-ylisocyanide (0.083 g). The mixture was stirred overnight at 65° C., then allowed to cool to room temperature, and concentrated under reduced pressure. To the obtained residue were added tetrahydrofuran (4 mL), water (40 muL) and a solution of 4 mol/L hydrogen chloride in 1,4-dioxane (340 muL), and the mixture was stirred for 1 hour at room temperature. To the reaction mixture were added water and a saturated aqueous solution of sodium bicarbonate, and the crude product was extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: methanol/ethyl acetate/n-hexane=0/60/40 to 0/100/0 to 20/80/0) to afford 2-nitro-N-[(R)-carbamoylphenylmethyl]-N-[(R)-6-chloro-4-fluoroindan-1-yl]nicotinamide (0.090 g). A suspension of Raney catalyst was prepared as follows. A mixture of Raney (registered trademark) 2800 nickel slurry in water, active catalyst (Sigma-Aldrich) (200 muL) and ethanol was stirred, and the solvent was removed by decantation. The catalyst was washed 3 times with ethanol, and ethanol (1 mL) was added to form a suspension.
0.09 g Triethylamine (0.046g) and benzaldehyde (0.048g) in addition to methanol (3mL) solution of (R) -6- chloro-4-fluoro-indan-1-ylamine hydrochloride(0.1g), at 65 It was stirred for 0.5 hours. The reaction mixture was allowed to cool to room temperature, <strong>[33225-72-8]2-nitro-nicotinic acid</strong> (0.083 g) and4-phenyl-cyclohexen-1-yl isocyanide a (0.083 g) was added and stirred overnight at 65 ° C.. After the reaction mixture was allowed to cool to roomtemperature, and then concentrated under reduced pressure. The obtained residue in tetrahydrofuran (4 mL), water (40 muL) and 4 mol / Lhydrogen chloride in 1,4-dioxane solution (340muL) was added, and stirred for 1 hour at room temperature. Water and saturated sodium bicarbonatesolution was added to the reaction mixture, the crude product was extracted with ethyl acetate. The organic layer was washed with water and brine,dried over anhydrous magnesium sulfate. The solvent was obtained by vacuum distillation residue was purified by silica gel column chromatography(eluting solvent methanol / ethyl acetate / n-hexane = 0/60 / 40-0 / 100 / 0-20 / 80/0), 2-nitro -N - [(R) - carbamoyl phenylmethyl] -N - was obtained[(R) -6- chloro-4-fluoro-indan-1-yl] nicotinamide (0.090 g). A suspension of Raney catalysts were prepared as follows. Raney (TM) 2800 nickel, slurryin water, stirring the mixture of ethanol and a suspension (200 muL) of active catalyst (Sigma-Aldrich), and the solvent was removed by decantation.The catalyst was washed 3 times with ethanol, ethanol (1 mL) was added and the suspension. The Raney catalyst suspension, under an argonatmosphere, 2-nitro -N - [(R) - carbamoyl phenylmethyl] -N - [(R) -6- chloro-4-fluoro-indan-1-yl] nicotinamide It added at room temperature in ethanol(1mL) solution of (0.090g), and the mixture was stirred under a hydrogen atmosphere for 5 hours. The catalyst was removed by filtration, and thefiltrate was concentrated under reduced pressure. The residue aminopropyl silica gel column chromatography (eluting solvent ethyl acetate /n-hexane = 90 / 10-100 / 0) to give the title compound (0.071 g).
  • 5
  • [ 33225-72-8 ]
  • [ 128798-39-0 ]
  • [ 100-52-7 ]
  • 2-amino-N-[(R)-carbamoylphenylmethyl]-N-[(R)-6-chloro-4-fluoroindan-1-yl]nicotinamide [ No CAS ]
  • 6
  • [ 33225-72-8 ]
  • (R)-6-chloro-4-fluoroindan-1-ylamine hydrochloride [ No CAS ]
  • [ 128798-39-0 ]
  • [ 100-52-7 ]
  • C35H30ClFN4O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
To a solution of (R)-6-chloro-4-fluoroindan-1-ylamine hydrochloride (0.1 g) in methanol (3 mL) were added triethylamine (0.046 g) and benzaldehyde (0.048 g), and the mixture was stirred for 0.5 hours at 65° C. The reaction mixture was allowed to cool to room temperature, and to the mixture were added <strong>[33225-72-8]2-nitronicotinic acid</strong> (0.083 g) and 4-phenylcyclohexen-1-ylisocyanide (0.083 g). The mixture was stirred overnight at 65° C., then allowed to cool to room temperature, and concentrated under reduced pressure. To the obtained residue were added tetrahydrofuran (4 mL), water (40 muL) and a solution of 4 mol/L hydrogen chloride in 1,4-dioxane (340 muL), and the mixture was stirred for 1 hour at room temperature. To the reaction mixture were added water and a saturated aqueous solution of sodium bicarbonate, and the crude product was extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: methanol/ethyl acetate/n-hexane=0/60/40 to 0/100/0 to 20/80/0) to afford 2-nitro-N--[(R)-carbamoylphenylmethyl]-N--[(R)-6-chloro-4-fluoroindan-1-y- l]nicotinamide (0.090 g). A suspension of Raney catalyst was prepared as follows. A mixture of Raney (registered trademark) 2800 nickel slurry in water, active catalyst (Sigma-Aldrich) (200 muL) and ethanol was stirred, and the solvent was removed by decantation. The catalyst was washed 3 times with ethanol, and ethanol (1 mL) was added to form a suspension. To a solution of 2-nitro-N--[(R)-carbamoylphenylmethyl]-N--[(R)-6-chloro-4-fluoroindan-1-y- l]nicotinamide (0.090 g) in ethanol (1 mL) was added the suspension of Raney catalyst at room temperature, and the mixture was stirred for 5 hours under hydrogen atmosphere. The catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by aminopropyl silica gel column chromatography (eluent:ethyl acetate/n-hexane=90/10 to 100/0) to afford the title compound (0.071 g).
  • 7
  • [ 3544-25-0 ]
  • [ 33225-72-8 ]
  • C14H10N4O3*C8H8O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
93.6% Compound 3 (16.8 g, 0.1 mol) was dissolved in acetonitrile (100 mL).Add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (24.9 g, 0.13 mol),Stir at room temperature for 2 hours.Compound 2 (17.18 g, 0.13 mol) was added,The temperature was raised to 90 ° C and kept for 6 hours.After completion of the reaction, the acetonitrile was evaporated to give an oily substance, and purified water (80 ml) was added thereto, and the mixture was stirred, and filtered, and rinsed with water.Compound 4 and dried to give 26.42g, 93.6percent yield
 

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