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Structure of 641-70-3

Chemical Structure| 641-70-3

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Product Details of [ 641-70-3 ]

CAS No. :641-70-3
Formula : C8H3NO5
M.W : 193.11
SMILES Code : C1=CC=C(C2=C1C(=O)OC2=O)[N+](=O)[O-]
MDL No. :MFCD00005921
InChI Key :ROFZMKDROVBLNY-UHFFFAOYSA-N
Pubchem ID :21631

Safety of [ 641-70-3 ]

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

Computational Chemistry of [ 641-70-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 5.0
Num. H-bond donors 0.0
Molar Refractivity 45.01
TPSA ?

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

89.19 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.37
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

1.12
Log Po/w (WLOGP)?

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

0.91
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.

0.63
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

-0.34
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.54

Water Solubility

Log S (ESOL):?

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

-1.99
Solubility 1.96 mg/ml ; 0.0101 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.

-2.59
Solubility 0.5 mg/ml ; 0.00259 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

-1.85
Solubility 2.72 mg/ml ; 0.0141 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.

-6.68 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

4.0 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)

2.27

Application In Synthesis of [ 641-70-3 ]

* 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 [ 641-70-3 ]

[ 641-70-3 ] Synthesis Path-Downstream   1~9

  • 1
  • [ 1454-85-9 ]
  • [ 641-70-3 ]
  • 3-nitro-phthalic acid-2-heptadecyl ester [ No CAS ]
  • 4
  • [ 253168-94-4 ]
  • [ 641-70-3 ]
  • 2-[1-(3-Ethoxy-4methoxyphenyl)-2-methylsunylethyl]-4nitroisoindoline-1,3-dione [ No CAS ]
  • 2-[1-(3-ethoxy-4-methoxyphenyl)-2-methyl-sulfonylethyl]-4-nitroisoindoline-1,3-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% In acetic acid; EXAMPLE 8 2-[1-(3-Ethoxy-4methoxyphenyl)-2-methylsunylethyl]-4nitroisoindoline-1,3-dione A stirred solution 1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethylamine (640 mg, 2.34 mmol) and 3-nitrophthalic anhydride (460 mg, 2.34 mmol) in acetic acid (10 mL) was heated at reflux for 15 h. The solvent was removed in vacuo to yield an oil. Chromatography of the resulting oil yielded 2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-nitroisoindoline-1,3-dione as a yellow solid (850 mg, 81% yield): mp, 110.0-114.0 C.; 1 H NMR (CDCl3); delta 1.47 (t, J=7.0 Hz, 3H, CH3), 2.90 (s, 3H, CH3), 3.71 (dd, J=4.3, 14.4 Hz, 1H, CHH), 3.85 (s, 3H, CH3), 4.10 (q, J=7.0 Hz, 2H, CH2), 4.58 (dd, J=10.7, 14.4 Hz, 1H, CHH), 5.93 (dd, J=4.2, 10.7 Hz, 1H, NCH), 6.84 (d, J=8.8 Hz, 1H, Ar), 7.11-7.15 (m, 2H, Ar), 7.89 (t, J=7.8 Hz, 1H, Ar), 8.08-8.13 (m, 2H, Ar); 13 C NMR (CDCl3) delta 14.67, 41.56, 49.19, 53.97, 55.96, 64.56, 111.52, 112.51, 120.62, 123.44, 127.35, 128.65, 128.84, 133.73, 135.48, 145.24, 148.68, 149.92, 162.53, 165.33; Anal Calcd for C20 H20 NO8 S: C, 53.57; H, 4.50; N, 6.23. Found: C, 53.54; H, 4.28; N, 6.32
  • 5
  • [ 824-72-6 ]
  • Phenyltrichlorophosphonium hexachlorophosphide [ No CAS ]
  • [ 641-70-3 ]
  • [ 117-21-5 ]
YieldReaction ConditionsOperation in experiment
81 wt.% With sodium hydroxide; B. 3-Nitrophthalic Anhydride Phenyltrichlorophosphonium hexachlorophosphide (4 g, 8.8 mM) was added to phenylphosphonic dichloride (10 ml). To this solutoin, 3 nitrophthalic anhydride (1.7 g, 8.8 mM) was added. The reaction mixture was heated to 170 C. for 12 hours, then cooled to room temperature and poured onto ice. After neutralizing with 50% aqueous sodium hydroxide, the reaction was extracted with ethyl acetate. The combined ethyl acetate extracts were washed with brine, dried over magnesium sulfate, and concentrated in vacuo to give 3-chlorophthalic anhydride (1.3 g, 81 wt. % yield) as a tan solid.
  • 6
  • [ 6789-94-2 ]
  • [ 641-70-3 ]
  • [ 759402-28-3 ]
YieldReaction ConditionsOperation in experiment
EXAMPLE 5 1-Ethyl-3-(3-nitrophthalimido)piperidine 3-Nitrophthalic anhydride (0.01 moles) and 3-amino-1-ethylpiperidine (0.01 moles) are reacted in a similar manner to that described in Example 4 to give the title compound in the form of the hydrochloride. Melting Point: >300 C.
  • 7
  • [ 67-56-1 ]
  • [ 641-70-3 ]
  • [ 13365-26-9 ]
YieldReaction ConditionsOperation in experiment
71% With sulfuric acid; In neat (no solvent); for 16h;Reflux; (2) Synthesis of dimethyl 3-nitrophthalate (compound 3) 3-Nitrophthalic anhydride (15 g, 77.7 mmol) from step (1) was dissolved in 200 mL of methanol and 5 mL of concentrated sulfuric acid was added. The mixture was heated to reflux for 16 hours. After cooled to room temperature, the reaction mixture was poured into ice water. The mixture was then filtered, and the resulted solid was washed with water and dried to give compound 3 (13.1 g, 71%).
65% With sulfuric acid; for 16h;Heating / reflux; Preparation of 3-nitro-phthalic Acid Dimethyl Ester, 2 To a stirred solution of 4-nitro-isobenzofuran-1,3-dione (150 g, 0.78 mol), 1, in 2 L of MeOH was added 50 mL of concentrated sulfuric acid. The reaction was heated to reflux for 16 hours. The mixture solution was cooled to room temperature and then poured into 3 L of ice water and resulted in a heavy white precipitate. This was triturated for 15 minutes and the precipitated was filtered off and the solid was washed with water thoroughly and dried to afford 120 g of 3-nitro-phthalic acid dimethyl ester, 2, as a white solid (65%). 1H NMR (300 MHz, DMSO-d6): 8.54 (d, J=7.25 Hz, 1H), 8.42 (d, J=7.82 Hz, 1H), 7.98 (t, J=8.20 Hz, 1H), 3.99 (s, 3H), 3.98 (s, 3H). 13C NMR: 52.03, 52.29, 111.02, 115.67, 119.08, 131.80, 133.68, 148.80, 167.64, 168.63.
With biocarbon material loaded with sulfonated polyaniline; In methanol; at 20℃; for 10h; (1) 3-nitrophthalic anhydride (3 mmol) was dissolved in methanol (15 mL). Add product B (6 mg), stir the reaction for 10 hours at room temperature, TLC detects the disappearance of 3-nitrophthalic anhydride and recovers product B by filtration.Concentrated under reduced pressure, Drying in vacuo gave dimethyl 3-nitrophthalate (687 mg, yield 95.7%, HPLC purity 96.0%).
  • 8
  • [ 253168-94-4 ]
  • [ 641-70-3 ]
  • 2-[1-(3-ethoxy-4-methoxyphenyl)-2-methyl-sulfonylethyl]-4-nitroisoindoline-1,3-dione [ No CAS ]
  • 9
  • [ 641-70-3 ]
  • [ 74-88-4 ]
  • [ 13365-26-9 ]
YieldReaction ConditionsOperation in experiment
90% With sodium hydrogencarbonate; In methanol; for 5h;Reflux; Weigh 1g of 3-nitrophthalic anhydride in methanol solution, stir at room temperature for 2h, then add 750mg NaHCO3 (1.5eq), slowly add methanol solution of CH3I (2.2eq) dropwise, transfer to 70 C and reflux for 3h, The reaction was detected by TLC. After the reaction was completed, the methanol was quenched and evaporated, extracted three times with ethyl acetate, and extracted once with saturated brine. The organic layers were combined, dried over anhydrous magnesium sulfate, filtered with suction, concentrated under reduced pressure, and then subjected to column chromatography Purification method to obtain intermediate 1, yield 90%.
 

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Technical Information

Categories

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