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Structure of 59483-54-4

Chemical Structure| 59483-54-4

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Product Details of [ 59483-54-4 ]

CAS No. :59483-54-4
Formula : C6H5ClN2O2
M.W : 172.57
SMILES Code : C1=CC=C(C(=C1N)[N+](=O)[O-])Cl
MDL No. :MFCD01317803
InChI Key :YADOEPHJIBKBCN-UHFFFAOYSA-N
Pubchem ID :101068

Safety of [ 59483-54-4 ]

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

Computational Chemistry of [ 59483-54-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 44.68
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.

1.19
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

2.25
Log Po/w (WLOGP)?

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

1.84
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.

0.88
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

-0.37
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.

-2.67
Solubility 0.373 mg/ml ; 0.00216 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.

-3.39
Solubility 0.0696 mg/ml ; 0.000403 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

-2.03
Solubility 1.61 mg/ml ; 0.00931 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

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.

-5.76 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)

1.9

Application In Synthesis of [ 59483-54-4 ]

* 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 [ 59483-54-4 ]

[ 59483-54-4 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 59483-54-4 ]
  • [ 120258-69-7 ]
  • 2
  • [ 59483-54-4 ]
  • [ 1000573-99-8 ]
YieldReaction ConditionsOperation in experiment
72% With N-Bromosuccinimide; In acetic acid; for 0.75h;Reflux; 5.00 g (28.973 mmol) of 3-chloro-2-nitroaniline and 5.05 g (28.394 mmol) of N-bromosuccinimide were dissolved in 250 ml acetic acid. The mixture was boiled under reflux for 45 min. After cooling, the reaction mixture was added to 1.5 1 water. The resultant precipitate was filtered off and dried under high vacuum. We obtained 5.25 g (72% of theor.) of the target compound.LC-MS (method 9): R, = 2.16 min; MS (Elmin): m/z = 251 [M-H]+. 1H-NMR (400 MHz, DMSO-D6): δ [ppm] = 6.40 (sbr, 2H), 6.83 (d, IH), 7.56 (d, IH).
68.6% With N-Bromosuccinimide; acetic acid; for 0.75h;Reflux; 4-Bromo-3-chloro-2-nitroaniline3-Chloro-2-nitroaniline (10 g, 57.9 mmol) and NBS (10.31 g, 57.9 mmol) were dissolved in AcOH (500 mL). The reaction mixture was stirred at reflux temperature for 45 min. After cooling, the reaction mixture was added to 1.5L of water. The resultant precipitate was filtered off and dried under high vacuum to give 10 g (68.6%) of the title compound.
67% With N-Bromosuccinimide; acetic acid; for 1h;Reflux; Intermediate 12A; 4-bromo-3-chloro-2-nitroaniline; 3-Chloro-2-nitroaniline (5.00 g, 29.0 mmol) was dissolved in glacial acetic acid (258 mL). N-Bromosuccinimide (5.06 g, 28.4 mmol) was added and the resulting mixture was refluxed for 1 hour. The reaction was cooled to room temperature and poured into water to give a precipitate that was filtered, rinsed with water and dried to constant weight to give the title compound (4.78 g, 67%o). .H NMR (400 MHz, CDCL3) δ ppm 7.46 (d, J= 9.0, 1H), 6.64 (d, J= 9.0, 1H), 4.74 (s, 2H).
62% With N-Bromosuccinimide; acetic acid;Inert atmosphere; Reflux; A solution of 3-chloro-2-nitroaniline (25.0 g 0.145 mol) and NBS (25.8 g 0.145 mol) in acetic acid (1 L) was heated at reflux under N2 overnight. Water (1 L) was added and the insoluble matter was collected by filtration to give the title compound (22.3 g, 62%) as a gray solid. LCMS-C (ES-API): rt 3.84 min; m/z 250.9, 252.9 [M+H]+. 1 H NMR (400 MHz, DMSO-de) d 7.56 (d, J = 9.2 Hz, 1 H), 6.84 (d, J = 9.2 Hz, 1 H), 6.41 (s, 2H).
23% With N-Bromosuccinimide; acetic acid; at 80℃; for 1.5h; In a 2 L three necked flask, a solution of 3-chloro-2-nitroaniline (60 g, 348 mmol) in AcOH (600 mL) was treated portionwise with NBS (61.9 g, 348 mmol). The resultant orange solution was heated at 80 C for 1.5 h. The reaction mixture was cooled to RT and was poured into stirred ice water (800 mL). The resultant orange precipitate was collected by filtration, washed with water (200 mL). The orange residue was collected and dissolved in EtOAc (500 mL). The solution was dried with MgSO4, filtered and the solvent was concentrated in vacuo to give an orange solid (86.5 g). The residue was recrystallised from 10% EtOAc/iso-Hexane (500 mL). The resultant solid was filtered, rinsing with iso-Hexane (100 mL), and dried in vacuo to afford a light orange solid (39.88 g, 158.6 mmol, 46%). The filtrate was concentrated in vacuo to give an orange solid. The residue was recrystallised from 10% Ac/iso-Hexane (250 mL). The resultant solid was filtered, rinsing with iso-Hexane (50 mL), and dried in vacuo to afford a light orange solid (20 g, 79.53 mmol, 23%).1H NMR in DMSO-d6: (7.55 (1H, d), 6.84 (1H, d), 6.40 (2H, s). Step
13g With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 0 - 20℃;Inert atmosphere; A solution of BS (10.31 g ) in DMF (25 mL) was added to a solution of 3- chloro-2-nitroaniline in DMF (100 mL) at 0 C. The resulting solution was stirred at 0 C for 1 hour then allowed to warm to room temperature and stirred at room temperature overnight. The orange solution was taken up in EtOAc and washed 3 times with water. Then the organic layer was dried (Na2S04) and the solvent was removed under reduced pressure. The residue was rinsed with hexanes and collected via filtration to provide 13 g of the title compound as a brown solid.
13 g With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 0 - 20℃; [0658] A solution ofNBS (10.31 g ) in DMF (25 mL) was added to a solution of 3-chloro- 2-nitroaniline in DMF (100 mL) at 0 C. The resulting solution was stirred at 0 C for 1 h, then allowed to warm to room temperature and stirred overnight. The orange solution was taken up in EtOAc and washed 3 times with water. Then the organic layer was dried (Na2SO4) and the solvent was removed under reduced pressure. The residue was rinsed with hexanes and collected via filtration to provide 13 g of brown solid.

  • 3
  • [ 55589-47-4 ]
  • [ 59483-54-4 ]
  • C23H25N5O [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In methanol; water; at 0 - 20℃; for 3h; To a mixture of X4-013-6 (1 g, 3.5 mmol) and 3-methylpicolinaldehyde (639 mg, 5.28 mmol) in MeOH (40 ml) was added a solution of NaOH (210 mg, 5.28 mmol) in H20 (2 mL) at 0 °C and the mixture was stirred at room temperature for 3 h. The pH was adjusted to 8 with 35percent HC1 aq., dried over anhydrous Na2SO4, filtered and concentrated in vacuum. The residue was purified by column chromatography to give X4-357-1 (1.15 g, 84.4 percent yield) as yellow solid. LCMS (Agilent LCMS 1200-6120, Column: Waters X-Bridge C18 (50 mm*4.6 mm*3.5 iim); Column Temperature: 40 °C; Flow Rate: 2.0 mL/min; Mobile Phase: from 90percent [(total 10mM AcONH4) water/CH3CN = 900/100 (v/v)] and 10percent [(total 10mM AcONH4) water/CH3CN = 100/900 (v/v)] to 10percent [(total 10mM AcONH4) water/CH3CN = 900/100 (v/v)] and 90percent [(total 10mM AcONH4) water/CH3CN = 100/900 (v/v)] in 1.6 mm, then under this condition for 2.4 mm, finally changed to 90percent [(total 10mM AcONH4) water/CH3CN = 900/100(v/v)] and 10percent [(total 10mM AcONH4) water/CH3CN = 100/900 (v/v)] in 0.1 mm and under thiscondition for 0.7 mm). Purity: 89.3 percent. Rt = 1.48 mm; MS Calcd.: 387.2; MS Found: 388.3 [M +H]t
  • 4
  • [ 59483-54-4 ]
  • [ 1000573-99-8 ]
  • 6-bromo-3-chloro-2-nitroaniline [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-Bromosuccinimide; acetic acid; for 0.75h;Reflux; A solution of 3-chloro-2-nitroaniline (25 g, 145 mmol) and N-bromosuccinimide (25.5 g, 143 mmol) inAcOH (600 mL) was refluxed for 45 mm. After cooling to RT, the reaction mixture was poured into ice-cold water (2 L). The precipitate was collected by filtration, washed with ice-cold water (2 x200 mL) anddried in a vacuum oven overnight, to give the title compounds (36 g) as a mixture of isomers (4-bromo/6-bromo in 9:1 ratio). 1H NMR (500 MHz, DMSO-d6): 7.56 (1H, d), 6.84 (1H, d), 6.40 (2H, 5).
With N-Bromosuccinimide; acetic acid; for 0.75h;Reflux; A solution of 3-chloro-2-nitroaniline (25 g, 145 mmol) and N-bromosuccinimide (25.5 g, 143 mmol) in AcOH (600 mL) was refluxed for 45 min. After cooling to RT, the reaction mixture was poured into ice-cold water (2 L). The precipitate was collected by filtration, washed with ice-cold water (2 x 200 mL) and dried in a vacuum oven overnight, to give the title compounds (36 g) as a mixture of isomers (4-bromo/6-bromo in 9:1 ratio). 1H NMR (500 MHz, DMSO-d 6) δ: 7.56 (1H, d), 6.84 (1H, d), 6.40 (2H, s).
 

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