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Chemical Structure| 1955-46-0 Chemical Structure| 1955-46-0
Chemical Structure| 1955-46-0

Methyl 5-nitroisophthalate

CAS No.: 1955-46-0

4.5 *For Research Use Only !

Cat. No.: A206002 Purity: 95%

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Product Details of [ 1955-46-0 ]

CAS No. :1955-46-0
Formula : C9H7NO6
M.W : 225.16
SMILES Code : O=C(O)C1=CC([N+]([O-])=O)=CC(C(OC)=O)=C1
MDL No. :MFCD00009793
InChI Key :ZCRNIIJXDRYWDU-UHFFFAOYSA-N
Pubchem ID :74776

Safety of [ 1955-46-0 ]

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

Calculated chemistry of [ 1955-46-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 6
Fraction Csp3 0.11
Num. rotatable bonds 4
Num. H-bond acceptors 6.0
Num. H-bond donors 1.0
Molar Refractivity 53.5
TPSA ?

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

109.42 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.99
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

1.54
Log Po/w (WLOGP)?

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

1.08
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.

0.54
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

-0.98
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.63

Water Solubility

Log S (ESOL):?

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

-2.22
Solubility 1.36 mg/ml ; 0.00603 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 0.0804 mg/ml ; 0.000357 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

-1.24
Solubility 13.1 mg/ml ; 0.0581 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.

-6.58 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

0.0
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)

2.07

Application In Synthesis of [ 1955-46-0 ]

* 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 [ 1955-46-0 ]

[ 1955-46-0 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 1955-46-0 ]
  • [ 28179-47-7 ]
YieldReaction ConditionsOperation in experiment
92% With hydrogen;palladium dihydroxide; In methanol; under 2585.81 Torr; for 5.0h; EXAMPLE 14 Methyl 5-((lR,2S)-2-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine- <n="88"/>l-carbonyl)cyclohexylcarbamoyl)biphenyl-3-carboxylateStep 1 : Preparation of 3-amino-5-(methoxycarbonyl)benzoic acid[00142] 20% Pd(OH)2 (0.50 g) was carefully wetted down under argon with methanol (5 mL) and then 3-(methoxycarbonyl)-5-nitrobenzoic acid (5.00 g, 22.2 mmol) in methanol (20 mL) was added. The mixture was then hydrogenated on a Parr Shaker apparatus for 5 hours at 50 psi. Under argon, the reaction was carefully filtered through a fiberglass filter paper. The filtrate was concentrated to give 3- amino-5-(methoxycarbonyl)benzoic acid (4.0 g, 20.5 mmol, 92% yield) of off-white solids as product. MS found: (M - H)+ = 194.
82% With hydrogen;palladium 10% on activated carbon; In methanol; under 2585.81 Torr; for 3.0h; A suspension of 3-(methoxycarbonyl)-5-nitrobenzoic acid (11.25 g, 50 mmol) and palladium on carbon (10 wt %, 1.0 g) in MeOH (10 mL) was shaken in hydrogenator under hydrogen at 50 psi for 3 h. The mixture was filtered and concentrated in vacuo to give the title compound (8.0 g, 82% yield): 1H NMR (CD3OD, 500 MHz) delta ppm 3.91 (3H, s), 7.53 (1H, m), 7.55 (1H, m), 7.92 (1H, m). HPLC retention time: 0.922 min (method A). MS (ESI) (M+H)+196.12.
71% With hydrogen;5% palladium over charcoal; In methanol; at 20℃; under 2585.81 Torr; for 2.5h; 30.0 g (133.2 mmol) monomethyl 5-nitro-isophthalate were dissolved in 200 ml of methanol and combined with 3.0 g Pd/C (5%). The mixture was hydrogenated for 2.5 hours in a Parr apparatus at ambient temperature under a hydrogen pressure of 50 psi. Then the catalyst was filtered off and the filtrate was evaporated down i. vac. Yield 18.4 g (71%) 6.3-a. RT(HPLC 1)=2.88 min
With hydrogenchloride;palladium; In tetrahydrofuran; diethyl ether; Preparation of 3-Amino-5-(methoxycarbonyl)benzoic Acid (Compound 68) To 2.75 g of mono-methyl 5-nitroisophthalate (5-(methoxycarbonyl)-3-nitrobenzoic acid), compound 67, dissolved in 30 mL of THF was added 100 mg of 10% palladium on carbon. The reaction was placed in a Parr hydrogenator under a H2 atmosphere of 45 psi and shaken for 16 hr. The solid palladium catalyst was removed by vacuum filtration through celite and 5 mL of 1N HCl in diethyl ether was added to the filtrate. After sitting for 12 hr, the solid was collected by vacuum filtration and was washed with ethyl acetate. This provided 1.82 g of the desired product. The product was identified by 1H NMR and mass spectroscopy and purity was assessed by RP-HPLC.
With hydrogen;palladium on activated charcoal; In tetrahydrofuran; methanol; under 750.075 Torr; Monomethyl-5-nitroisophthalate (50 g, 220 mmol, 1 eq) is dissolved in a mixture of 650 ml of MeOH and 350 ml of THF. 3 g of Pd/C are added, and the reaction mixture is hydrogenated overnight under 1 bar of H2 and then filtered. The filtrate is concentrated, and the residue is dissolved in a mixture of THF (200 ml) and aq NaHCO3 (400 ml). CbzCI (62 ml, 50% in toluene, 184 mmol, 0.9 eq) is added, the reaction mixture is stirred for 1 h, CbzCI (31 ml, 50% in toluene, 92 mmol, 0.45 eq) is added, and the reaction mixture is stirred overnight. The white solid formed is washed with water and diethyl ether to give the product.MS (ES-): 328 = [M-HT.HPLC (Nucleosil C18HD, 4x70 mm, 3 mum, 20-100% MeCN (6 min), 100% MeCN (1.5 min)) retention time: 4.36 min.1H-NMR (400 MHz, DMSO-d6): 8.40 (s, 1H), 8.38 (s, 1H), 8.17 (s, 1H), 7.50-7.37 (m, 5H),5.21 (s, 2H), 3.92 (s, 3H).
With hydrogen;palladium on activated charcoal; In tetrahydrofuran; methanol; under 750.075 Torr; a) 5-Benzyloxycarbonylamino-isophtalic acid monomethylesterMonomethyl-5-nitroisophtalate (50 g, 220 mmol, 1 eq) is dissolved in a mixture of 650 ml of MeOH and 350 ml of THF. 3 g of Pd/C are added, and the reaction is hydrogenated over night under 1 bar of hydrogen. The reaction mixture is then filtered and concentrated to give the amine as a crude product, which is then dissolved in a mixture of THF (200 ml) and <n="37"/>aqueous sodium bicarbonate (400 ml). CbzCI (62 ml, 50% in toluene, 184 mmol, 0.9 eq) are added to the reaction mixture, and the reaction is stirred for 1 hour. CbzCI (31 ml, 50% in toluene, 92 mmol, 0.45 eq) are added, and the reaction is stirred over night. The white solid which crashes out, is washed with water and diethyl ether to give the product. 1 H-NMR (400 MHz, dmso-d6): 8.40 (s, 1 H), 8.38 (s, 1 H), 8.17 (s, 1 H), 7.50-7.37 (m, 5H), 5.21 (s, 2H), 3.92 (s, 3H).
With hydrogen;palladium on activated carbon; In methanol; under 2585.81 Torr; for 3.0h; Step G (I): 3-ammo-5-(methoxycarbonyl)benzoic acid.; A suspension of 3-(methoxycarbonyl)-5-nitrobenzoic acid (20.0 g) and palladium on carbon (5 wt%, 4.0 g) in MeOH (600 mL) was shaken in hydrogenator under hydrogen at 50 psi for 3 h. The mixture was filtered and concentrated in vacuo to give the EPO <DP n="42"/>title compound: 1H NMR (CD3OD, 500 MHz) delta ppm 3.90 (3H, s), 7.52 (IH5 m), 7.55 (IH, m), 7.92 (IH, m). MS (ESI) (M-H)" 194.08.

 

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