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Structure of 601-89-8

Chemical Structure| 601-89-8

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Product Details of [ 601-89-8 ]

CAS No. :601-89-8
Formula : C6H5NO4
M.W : 155.11
SMILES Code : OC1=CC=CC(O)=C1[N+]([O-])=O
MDL No. :MFCD00007124
InChI Key :ZLCPKMIJYMHZMJ-UHFFFAOYSA-N
Pubchem ID :11760

Safety of [ 601-89-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302+H312+H332-H315-H319-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 601-89-8 ] 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 4.0
Num. H-bond donors 2.0
Molar Refractivity 39.31
TPSA ?

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

86.28 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.24
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

1.56
Log Po/w (WLOGP)?

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

1.01
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.

-0.3
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

-1.25
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.45

Water Solubility

Log S (ESOL):?

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

-2.12
Solubility 1.17 mg/ml ; 0.00755 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.

-2.98
Solubility 0.162 mg/ml ; 0.00104 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

-0.61
Solubility 37.7 mg/ml ; 0.243 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

Yes
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)

1.67

Application In Synthesis of [ 601-89-8 ]

* 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 [ 601-89-8 ]

[ 601-89-8 ] Synthesis Path-Downstream   1~9

  • 1
  • [ 6665-97-0 ]
  • [ 107-06-2 ]
  • [ 601-89-8 ]
  • 2
  • [ 601-89-8 ]
  • [ 77-78-1 ]
  • [ 3114-61-2 ]
  • [ 6665-97-0 ]
  • 3
  • [ 601-89-8 ]
  • [ 77-78-1 ]
  • [ 6665-97-0 ]
YieldReaction ConditionsOperation in experiment
99% With potassium carbonate; In acetone; for 1.0h;Inert atmosphere; Reflux; To a solution of 2-nitroresorcinol 49 (4.80 g, 30.9 mmol) in acetone (30 mL) was added K2CO3 (21.39 g, 155 mmol) under nitrogen atmosphere. Dimethylsulfate (8.80 mL, 92.8 mmol) was then added and the mixture obtained was heated to reflux for 1 h. After cooling to room temperature, the solvent was removed in vacuo. The solid obtained was washed with triethylamine and water, then filtered and dried (MgSO4) to give pure compound 5055 (5.6 g, 99%) as a white solid; TLC Rf (EtOAc) = 0.73; 1H NMR (CDCl3, 400 MHz) δ (ppm) 3.88 (s, 6H, 2OCH3), 6.63 (d, J = 8.6 Hz, 2H, ArH), 7.33 (t, J = 8.6 Hz, 1H, ArH).
  • 4
  • [ 601-89-8 ]
  • [ 74-88-4 ]
  • [ 6665-97-0 ]
YieldReaction ConditionsOperation in experiment
97% With potassium carbonate; In acetone; at 60 - 70℃; MeI (3.0 mL, 48.3 mmol) was added to mixture of 77 (2.50 g, 16.1 mmol) and K2CO3 (4.46 g, 325 mesh, 32.3 mmol) in acetone (250 mL). The reaction mixture was heated to 60-70 C. (bath temperature) over night under N2. The mixture was concentrated in vacuo and the residue was partitioned between EtOAc (200 mL) and water (100 mL). The aqueous layer was extracted with EtOAc (2×100 mL). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo to yield 78 as a yellow solid (2.87 g, 97%) which was used in the next step without further purification.
With potassium carbonate; In acetone;Heating; Inert atmosphere; 1,3-Dimethoxy-2-nitro-benzene (78) MeI (3.0 mL, 48.3 mmol) was added to mixture of 77 (2.50 g, 16.1 mmol) and K2CO3 (4.46 g, 325 mesh, 32.3 mmol) in acetone (250 mL). The reaction mixture was heated to 6070 C. (bath temperature) over night under N2. The mixture was concentrated in vacuo and the residue was partitioned between EtOAc (200 mL) and water (100 mL). The aqueous layer was extracted with EtOAc (2×100 mL). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo to yield 78 as a yellow solid (2.87 g, 97%) which was used in the next step without further purification.
  • 5
  • [ 601-89-8 ]
  • [ 3114-61-2 ]
  • 7
  • [ 601-89-8 ]
  • [ 77-78-1 ]
  • [ 3114-61-2 ]
YieldReaction ConditionsOperation in experiment
37% With sodium hydroxide; In water; at 40℃; for 0.25h; Dimethylsulfate (2.7 mL, 0.058 mmol) was added carefully to 2-nitrobenzene-1,3-diol (2.5 g, 0.232 mmol) and the mixture was stirred vigorously while 10% NaOH solution (21 mL) was added and the temperature was kept below 40 C. After about 15 min, the mixture was cooled and then filtered. The filtrate was collected and acidified with 10% HCl, and extracted with ether (3×25 mL). The organic layer was dried (MgSO4), filtered, and concentrated under vacuum. Chromatography (10-30% EtOAc/hexanes) provided 9A10 (1 g, 37%).
  • 8
  • [ 601-89-8 ]
  • [ 74-88-4 ]
  • [ 3114-61-2 ]
YieldReaction ConditionsOperation in experiment
32% With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 7.0h; To a stirred solution of 28 (25.0 g, 161 mmol) in DMF (500 mL) were added K2CO3 (6.80 g, 49.2 mmol) and MeI (11.0 mL, 177 mmol). After stirring for 7 h at room temperature, the reaction mixture was concentrated in vacuo and diluted with water. The resulting mixture was washed with EtOAc; the aqueous layer was acidified with 1 mol/L HCl and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by silica gel column chromatography (n-hexane-EtOAc = 2:1) to give 29 (8.78 g, 51.9 mmol, 32%) as a yellow oil. 1H NMR (CDCl3, 400 MHz): δ 3.95 (3H, s), 6.54 (1H, dd, J = 8.6, 1.2 Hz), 6.71 (1H, dd, J = 8.6, 1.2 Hz), 7.40 (1H, t, J = 8.6 Hz), 10.22 (1H, s).
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 7.0h; 3-Methoxy-2-nitrophenol To a solution of 2-nitroresoreinol (25.0 g) in DMF (500 mL) were added potassium carbonate (6.8 g) and methyl iodide (11.0 mL), followed by stirring at room temperature for 7 hours. The solvent was evaporated under reduced pressure, and then to the residue was added water, followed by washing with ethyl acetate. The aqueous layer was acidified with hydrochloric acid and extracted with ethyl acetate. The extracted layer was washed with saturated brine and dried over anhydrous sodium sulfate, and the solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1) to obtain the desired product (8.78 g) as a yellow oil. 1H NMR (CDCl3, 400 MHz): δ 3.95 (3H, s), 6.54 (1H, dd, J=8.6, 1.2 Hz), 6.71 (1H, dd, J=8.6, 1.2 Hz), 7.40 (1H, t, J=8.6 Hz), 10.22 (1H, s).
1.6 g With potassium carbonate; In N,N-dimethyl-formamide; at 0 - 20℃; for 0.5h; 5 g of 2-nitrobenzene-1,3-diol was dissolved in N,N-dimethylformamide (75 mL), and then potassium carbonate (1.3 g, 0.3 equivalent) and methyl iodide (2.23 mL, 1.1 equivalents) were added thereto at 0 C., followed by stirring at room temperature for 30 minutes. The formation of the product was confirmed by TLC, and then distilled water was added to stop the reaction, followed by extraction using ethyl acetate. The organic phase was washed by 2 M hydrochloric acid (20 mL) and then dried over anhydrous magnesium sulfate, followed by filtration, and thus obtaining 1.6 g of the title compound by purification of the residue obtained by vacuum concentration of the filtrate through silica gel column chromatography (hexane:ethyl acetate=85:15).MS (ESI) m/z: 168 (M-H)-
1.6 g In N,N-dimethyl-formamide; at 0 - 20℃; for 0.5h; 5 g of 2-nitrobenzene-1,3-diol was dissolved in N,N-dimethylformamide (75 mL), and then potassium carbonate(1.3 g, 0.3 equivalent) and methyl iodide (2.23 mL, 1.1 equivalents) were added thereto at 0C, followed by stirring atroom temperature for 30 minutes. The formation of the product was confirmed by TLC, and then distilled water wasadded to stop the reaction, followed by extraction using ethyl acetate. The organic phase was washed by 2 M hydrochloricacid (20 mL) and then dried over anhydrous magnesium sulfate, followed by filtration, and thus obtaining 1.6 g of thetitle compound by purification of the residue obtained by vacuum concentration of the filtrate through silica gel columnchromatography (hexane:ethyl acetate = 85:15).MS (ESI) m/z: 168 (M-H)-

 

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