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Chemical Structure| 20191-74-6 Chemical Structure| 20191-74-6
Chemical Structure| 20191-74-6

2-Ethyl-5-nitroaniline

CAS No.: 20191-74-6

4.5 *For Research Use Only !

Cat. No.: A136993 Purity: 97%

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Product Details of [ 20191-74-6 ]

CAS No. :20191-74-6
Formula : C8H10N2O2
M.W : 166.18
SMILES Code : NC1=CC([N+]([O-])=O)=CC=C1CC
MDL No. :MFCD00034056
InChI Key :MMZWMCKTKJKIMC-UHFFFAOYSA-N
Pubchem ID :4155478

Safety of [ 20191-74-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302+H312+H332
Precautionary Statements:P280

Calculated chemistry of [ 20191-74-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 49.44
TPSA ?

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

71.84 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.41
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

2.3
Log Po/w (WLOGP)?

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

1.75
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.

0.94
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

1.23

Water Solubility

Log S (ESOL):?

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

-2.56
Solubility 0.461 mg/ml ; 0.00277 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.

-3.45
Solubility 0.0594 mg/ml ; 0.000358 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

-2.2
Solubility 1.04 mg/ml ; 0.00627 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.

-5.68 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

3.0 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)

1.86

Application In Synthesis of [ 20191-74-6 ]

* 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 [ 20191-74-6 ]

[ 20191-74-6 ] Synthesis Path-Downstream   1~29

  • 2
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YieldReaction ConditionsOperation in experiment
52% Step3. A solution of sulfuric acid (98percent, 39 g, 390.00 mmol) in water (160 mL) was added to <strong>[20191-74-6]2-ethyl-5-nitrobenzenamine</strong> (12.9 g, 69.94 mmol, prepared as described in Step 2 above). The mixture was cooled to 0-5 0C, and a solution of sodium nitrite (5.63 g, 81.59 mmol) in water (20 mL) was then added. The resulting solution was maintained for 30 min at 0-5 0C. Sulfuric acid (65percent, 600 g, 3.98 mol) was then added, and the temperature was maintained at reflux for 1 hr. The reaction mixture was cooled in a bath of iced water, and the product was extracted with ethyl acetate. The organic layers were combined and washed with aqueous saturated sodium bicarbonate and brine (200 mL). The solution was dried (anhydrous MgSO-i), filtered, and concentrated. The residue was purified by eluting through a column with a 1 :10 (v/v) ethyl acetate/petroleum ether solvent system to afford 7.65 g (52 percent yield) of 2-ethyl-5-nitrophenol as a red solid.
With sulfuric acid; water; sodium nitrite; at 0 - 5℃; for 1.5h;Heating / reflux; Step 3; A solution of sulfuric acid (98percent, 39 g, 390.00 mmol) in water (160 mL) was added to <strong>[20191-74-6]2-ethyl-5-nitrobenzenamine</strong> (12.9 g, 69.94 mmol, prepared as described in Step 2 <n="55"/>above). The mixture was cooled to 0-5 0C5 and a solution of sodium nitrite (5.63 g, 81.59 mmol) in water (20 mL) was then added. The resulting solution was maintained for 30 minutes at 0-5 0C. Sulfuric acid (65percent, 600 g, 3.98 mol) was then added, and the temperature was maintained at reflux for 1 hr. The reaction mixture was cooled in a bath of iced water, and the product was extracted with ethyl acetate. The organic layers were combined and washed with aqueous saturated sodium bicarbonate and brine. The solution was dried (MgSO-j), filtered and concentrated. The residue was purified by eluting through a column with a 1 : 10 ethyl acetate/petroleum ether solvent system to afford 7.65 g of 2-ethyl-5-nitrophenol as a red solid.
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  • [ 578-54-1 ]
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YieldReaction ConditionsOperation in experiment
80.1% With sulfuric acid; nitric acid; at 0 - 20℃; for 0.5h; 2-ethylaniline (24.2 g, 0.2 mol) was added to concentrated sulfuric acid (100 ml).Cooled to below 0 ° C,Fuming nitric acid (18.6 g, 0.3 mol) was slowly added dropwise,The mixture was stirred at room temperature for 30 min.The reaction solution was poured into ice water (1000 ml)Slowly add 50percent sodium hydroxide solution to adjust the pH to about 8.filter,The cake was recrystallized from petroleum ether,Yielding yellow needle-shaped solid 2 (26.6 g, 80.1percent),
75.3% With sulfuric acid; nitric acid; at 0 - 5℃; for 0.5h; 2- Ethyl aniline (12.1g, 0.1mol) was dissolved in concentrated sulfuricacid (50mL), cooled to 0-5 ° C, and slowly added dropwise fuming nitric acid (9.3g,0.15mol), Bi drops, heat stirring 30min. The reaction solution was poured intoice-water (a 500 mL), and solid sodium hydroxide was added slowly under cooling was adjusted to pH7 -, a solidprecipitated. After filtration cake was dried and recrystallized fromcyclohexane to give yellow crystals 12.5g, yield 75.3percent
17% 2-ethylaniline (12. Ig, 99.8mmol, 1 equiv) was dissolved in concentrated sulphuric acid (50ml) and cooled down to O0C. Fuming nitric acid (9.3g, 147.6mmol, 1.5 equiv) was then added slowly keeping the temperature below 5°C. The reaction was left warm up to room temperature and stirred overnight. The reaction mixture was poured onto ice- water (250ml) and neutralised with sodium hydroxide 6M. The solid was filtered off and dried in an oven to remove as much water as possible. The red solid was then taken up in petrol (250ml x 4) and decanted over filter paper to crystallise out the desired compound as yellow solid. (2.7g, 17percent). IH NMR spectra were recorded at ambient temperature using a Bruker Advance DRX (400MHz) spectrometer, both with a triple resonance 5mm probe. Chemical shifts are expressed in ppm relative to tetramethylsilane.1H NMR (CDCl3, 400MHz) delta= 7.51 (d, J = 8Hz, IH), 7.43 (s, IH), 7.10 (d, J = 8Hz, IH), 3.7 (br s, 2H), 2.5 (q, J = 7Hz, 2H), 1.21 (t, J = 7Hz, 3H).
Example 2 1-(4-(4-(4-(3-methyl-1H-indazol-6-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)phenyl)piperazin-1-yl)ethanone and N4-(3-methyl-1H-indazol-6-yl)-N2-(4-(piperazin-1-yl)phenyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine To a solution of 2-ethylaniline (12.1 g, 0.1 mol) in conc. H2SO4 (50 mL) at 0° C. was added fuming HNO3 (9.3 g) drop wise. After stirring at ambient temperature for 30 min, the mixture was poured into ice-water, and 2 N NaOH was added to neutralize the excess acid. The resulting reddish-brown solid was collected by filtration and washed with petroleum ether to give 2-ethyl-5-nitroaniline as crude product (9 g).
With sulfuric acid; potassium nitrate; 5-Amino-2-chlorophenol1 2d was synthesized from 2-amino-5-nitrophenol 5 in two steps: 1) formation of the diazonium salt with NaNO2 and reaction with CuCl to give the corresponding 2-chloro-5-nitrophenol 6 in 68percent yield and 2) careful reduction of the nitro group with H2 (1 atm) in presence of Adam's catalyst to give the final amine derivative in 57percent yield (Scheme 2).5-Amino-2-ethyl/n-prorhoyl/z-propylphenol 2e-g was synthesized in four steps from the corresponding 2-emyl/rc-propyl/z-propylamline 7e-g. The first step was nitration with potassium nitrate in presence of sulfuric acid to give exclusively the corresponding 5-nitro-2- alkylaniline2 8e-g; reaction with NaNO2, followed by reaction with H2O at 8O0C for 2h gave the corresponding 5-nitro-2-alkylphenol derivatives3 9e-g and finally, hydrogenation of the nitro group gave the corresponding amine derivatives 2e-g (Scheme X). 2-Amine-4-hydroxybenzonitrile4 2h was obtained from 2-methoxy-4-nitrobenzonitrile 10 by hydrolisis of the methyl ether with LiCl and posterior, reduction of the nitro group with SnCl2.2H2O in presence of 6N HCl (Scheme 2).

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  • aqueous ammonium sulfide solution [ No CAS ]
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  • N-(4-ethyl-3-(3-methylbut-2-enyloxy)phenylthiazol)-2-amine [ No CAS ]
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  • 6-Bromo-7-ethyl-5-nitro-1,4-dihydro-quinoxaline-2,3-dione [ No CAS ]
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