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Chemical Structure| 138229-59-1 Chemical Structure| 138229-59-1

Structure of 138229-59-1

Chemical Structure| 138229-59-1

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Product Details of [ 138229-59-1 ]

CAS No. :138229-59-1
Formula : C9H7NO5
M.W : 209.16
SMILES Code : O=C(OC)C1=CC=CC(C=O)=C1[N+]([O-])=O
MDL No. :MFCD14706049
InChI Key :NSLOBVGASZUPDO-UHFFFAOYSA-N
Pubchem ID :44549250

Safety of [ 138229-59-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335-H412
Precautionary Statements:P261-P273-P305+P351+P338

Computational Chemistry of [ 138229-59-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 6
Fraction Csp3 0.11
Num. rotatable bonds 4
Num. H-bond acceptors 5.0
Num. H-bond donors 0.0
Molar Refractivity 51.93
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.

1.11
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

1.07
Log Po/w (WLOGP)?

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

1.19
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.

0.26
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

-0.25
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.68

Water Solubility

Log S (ESOL):?

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

-1.84
Solubility 3.0 mg/ml ; 0.0144 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.

-2.53
Solubility 0.611 mg/ml ; 0.00292 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

-1.81
Solubility 3.24 mg/ml ; 0.0155 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.

-6.82 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.

0.55

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)

2.1

Application In Synthesis of [ 138229-59-1 ]

* 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 [ 138229-59-1 ]

[ 138229-59-1 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 132874-06-7 ]
  • [ 138229-59-1 ]
YieldReaction ConditionsOperation in experiment
78% With 4-methylmorpholine N-oxide; In acetonitrile; at 20.0℃; for 2.0h;Molecular sieve; Inert atmosphere; Compound 2 (2.74 g, 10 mmol) was weighed into a 150 mL single-necked flask, and a mixture (0.2 M) of molecular sieve in acetonitrile was added to dissolve it. Under the protection of nitrogen, N-methylmorpholine-N-oxide (2.34) was added. g, 20 mmol), reacted at room temperature for 2 hours, concentrated and poured into water, extracted three times with EA, the organic phase was washed with 1N HCl, brine, dried, filtered, concentrated, and subjected to column chromatography (eluent is petroleum ether : Ethyl acetate = 80: 1) to give Compound 3 (1.63 g, 78%) as a pale yellow solid.
74% With 4-methylmorpholine N-oxide; In acetonitrile; at 20.0℃; for 1.5h; Step C; Methyl 3-Formyl-2-nitrobenzoate; Add N-methylmorpholine oxide (NMO, 6.10 g, 52.07 mmol) to a mixture of <strong>[132874-06-7]methyl 3-bromomethyl-2-nitrobenzoate</strong> (7.13 g, 26.023 mmol) and 4 A molecular sieves (35.32 g) in acetonitrile (150 mL) = at room temperature under nitrogen and stir for 1.5 h. Dilute the mixture with ethyl acetate (600 mL), filter the mixture by vacuum filtration and wash the filtrate with water (100 mL), 1 N HC1 (100 mL) and brine (150 mL) and dry over Na2S04. Remove the solvents under reduced pressure and purify the residue by flash column chromatography on silica gel, eluting with ethyl acetate/hexanes (1: 3), to provide methyl 3-formyl-2-nitrobenzoate as an off-white solid (4.04 g, 74%) : 1H NMR (CDC13) 8 3.95 (s, 3H), 7.77 (t, 1H), 8. 18 (dd, 1H), 8.28 (dd, 1H), 9. 98 (s, 1H).
54% With 4-methylmorpholine N-oxide; In acetonitrile; at 20.0℃; for 12.0h; To a mixture of Compound F (1.97 g, 7.18 mmol) in MeCN (20 mL) was added N- methylmorpholine N-oxide (2.15 g, 17.9 mmol) at ambient temperature, and the reaction mixture was stirred for 12 h. The reaction mixture was diluted with EtOAc, washed with water, 1 M HCl and brine. The organic extracts were dried over Na2S04, filtered and evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel using 5% EtO Ac/petroleum ether to provide Compound G (824 mg, 3.93 mmol) in 54% yield. MR (400 MHz, CDCb) delta 9.96 (s, 1H), 8.26 (d, J= 7.9 Hz, 1H), 8.18 (d, J = 7.9 Hz, 1H), 7.77 (t, J= 7.9 Hz, 1H), 3.93 (s, 3H). MS (ES -) m/z: C9H7NO5 requires 209, found 208 (M - H)". Physical state: Off- white solid; R = 0.6 (mobile phase: EtOAc/hexanes, 1 :9).
With 4-methylmorpholine N-oxide; In acetonitrile; at 20.0℃;Molecular sieve; Step 3: Methyl 3-formyI-2-nitrobenzoate (A3); To a mixture of (A2) (1.0 eq.) and 4A mol. sieves in MeCN (0.2M) at RT was addedNMMO (2.0 eq.) and the reaction mixture was stirred for 1.5 hr under N2 atmosphere. Then, the mixture was diluted with EtOAc, filtered and the filtrate was washed with H2O, IN HCl, brine <n="37"/>and dried (Na2SO4). Evaporation of the solvent gave (A3) as a white solid which was used in the next step without further purification. 1H NMR (400MHz, CDCl3, 300K) delta 9.96 (IH, s), 8.26 (IH, d, J= 7.9 Hz), 8.18 (IH, d, J = 7.9 Hz), 7.77 (IH, t, J = 7.9 Hz), 3.93 (3H, s). MS (ES) C9H7NO5 requires: 209, found: 208 (M-H)'.
With 4-methylmorpholine N-oxide; In acetonitrile; at 20.0℃; for 1.5h;Molecular sieve; Step 3: Methyl 3-formyl-2-nitrobenzoate (A3); To a mixture of (A2) and 4A mol. sieves (15 g) in MeCN (0.2M) at RT was added NMMO (2.0 eq.) and the reaction mixture was stirred for 1.5 hr under N2 atmosphere. Then, the mixture was diluted with EtOAc, filtered and the filtrate was washed with H2O, IN HCl, brine and dried (Na2SO4). Evaporation of the solvent gave (A3) as a white solid which was used in the next step without further purification. 1H NMR (400MHz, CDC13, 3OOK) delta 9.96 (IH, s), 8.26 (IH, d, J= 7.9 Hz), 8.18 (IH, d, J = 7.9 Hz), 7.77 (IH, t, J = 7.9 Hz), 3.93 (3H, s). MS (ES) C9H7NO5 requires: 209, found: 208 (M-H)".

  • 2
  • [ 6398-87-4 ]
  • [ 138229-59-1 ]
  • [ 952479-77-5 ]
 

Historical Records

Technical Information

• Acyl Group Substitution • Barbier Coupling Reaction • Baylis-Hillman Reaction • Benzylic Oxidation • Birch Reduction • Blanc Chloromethylation • Bouveault-Blanc Reduction • Bucherer-Bergs Reaction • Catalytic Hydrogenation • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Chaykovsky Reaction • Corey-Fuchs Reaction • Ester Cleavage • Fischer Indole Synthesis • Friedel-Crafts Reaction • Grignard Reaction • Hantzsch Dihydropyridine Synthesis • Henry Nitroaldol Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Hydrogenolysis of Benzyl Ether • Julia-Kocienski Olefination • Knoevenagel Condensation • Leuckart-Wallach Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Mukaiyama Aldol Reaction • Nozaki-Hiyama-Kishi Reaction • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Alkylbenzene • Preparation of Amines • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reactions with Organometallic Reagents • Reformatsky Reaction • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Specialized Acylation Reagents-Carbodiimides and Related Reagents • Stetter Reaction • Stobbe Condensation • Tebbe Olefination • Ugi Reaction • Vilsmeier-Haack Reaction • Wittig Reaction • Wolff-Kishner Reduction

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