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Chemical Structure| 23218-93-1 Chemical Structure| 23218-93-1

Structure of 23218-93-1

Chemical Structure| 23218-93-1

Methyl 3-amino-5-nitrobenzoate

CAS No.: 23218-93-1

4.5 *For Research Use Only !

Cat. No.: A245181 Purity: 97%

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Product Details of [ 23218-93-1 ]

CAS No. :23218-93-1
Formula : C8H8N2O4
M.W : 196.16
SMILES Code : O=C(OC)C1=CC([N+]([O-])=O)=CC(N)=C1
MDL No. :MFCD00461253
InChI Key :HZVBRLJDOZZHFL-UHFFFAOYSA-N
Pubchem ID :2756518

Safety of [ 23218-93-1 ]

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

Computational Chemistry of [ 23218-93-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 3
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 50.95
TPSA ?

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

98.14 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.21
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

1.33
Log Po/w (WLOGP)?

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

0.97
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

-1.14
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.53

Water Solubility

Log S (ESOL):?

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

-2.01
Solubility 1.9 mg/ml ; 0.0097 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.

-2.99
Solubility 0.2 mg/ml ; 0.00102 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

-1.5
Solubility 6.2 mg/ml ; 0.0316 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.

-6.55 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)

2.08

Application In Synthesis of [ 23218-93-1 ]

* 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 [ 23218-93-1 ]

[ 23218-93-1 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 2702-58-1 ]
  • [ 23218-93-1 ]
YieldReaction ConditionsOperation in experiment
88% With diammonium sulfide; In methanol; for 5h;Reflux; The solution of (NH4)2S23 used for this reaction was prepared by adding a solution of Na2S·9H2O (15.00g, 62.47mmol) in 100mL of MeOH to a suspension of NH4Cl (13.40g, 250.50mmol) in 100mL of MeOH and separating the solid material after 30min of stirring at room temperature. The resulting solution was added within 40min to a solution of 16 (6.20g, 27.42mmol) in 250mL of boiling MeOH and heated at reflux for 5h. After cooling down, the resulting precipitate of sulfur was filtered off and the pH was adjusted to 5 with 1M HCl and the solvent was removed under vacuum. The crude product was extracted with 250mL of AcOEt, washed with water, brine and dried over MgSO4 and concentrated in vacuo. Purification by silica gel column chromatography (30% acetone in hexane) afforded pure product 17 (4.73g, 88%) as an orange solid. 1H and 13C NMR data are in agreement with published data.24 1H NMR (400MHz, acetone-d6) delta: 7.93 (1H, dd, J 2.1, 1.4Hz, arom.), 7.71 (1H, t, J 2.2Hz, arom.), 7.67 (1H, dt J 2.2, 0.8Hz, arom.), 5.66 (2H, s, NH2), 3.91 (3H, s, OMe). 13C NMR (100MHz, acetone-d6) delta: 166.0, 151.1, 150.3, 133.1, 20.9, 112.2, 111.9, 52.8. Rf (30% acetone/hexane) 0.37. MS(EI): m/z (%)=197.1 (10), 196.1 (100, M+), 165.1 (33), 150.1 (20), 138.1 (8), 135.1 (22), 122.1 (35), 107.1 (17), 91.1 (23), 90.1 (10), 79.1 (8), 63.1 (20), 52.1 (9).
  • 2
  • [ 2702-58-1 ]
  • [ 23218-93-1 ]
  • 3-hydroxyamino-5-nitro-benzoic acid methyl ester [ No CAS ]
  • 3
  • [ 23218-93-1 ]
  • [ 151-50-8 ]
  • [ 99066-80-5 ]
  • 4
  • [ 23218-93-1 ]
  • 3-nitro-5-sulfinylamino-benzoic acid methyl ester [ No CAS ]
  • 5
  • [ 23218-93-1 ]
  • [ 36138-28-0 ]
YieldReaction ConditionsOperation in experiment
Example 9; Preparation of (3-{3-Chloro-5-[4-(2-fluoro-phenyl)-piperazine-1-sulfonyl]- phenyl}-4-cyano-pyrrol-1-yl)-acetic acid , sodium salt; a) 3-Chloro-5-nitro-benzoic acid methyl ester; To a solution of commercially available <strong>[23218-93-1]3-amino-5-nitro-benzoic acid methyl ester</strong> (32.0 g, 0.163mol) in cone HCI (332 ml) and AcOH (464 ml) at 00C is added NaNO2 (11.28 g, 0.163 mol) in water (20 ml) dropwise over 20 minutes, maintaining, the reaction temperature below O0C . The reaction mixture is stirred at 00C for 1 hour. The reaction mixture is added dropwise to a stirred solution of copper(l)chloride (19.4 g, 0.1956 mmol) in water (200 ml) over 45 minutes and the maximum temperature is kept at 210C. After 70 minutes at room temperature, the reaction mixture is poured slowly into stirring water and extracted with EtOAc. The combined organic layers are stirred with saturated sodium bicarbonate solution. The organic layer is separated, is washed with water, brine, dried over MgSO* After filtration the solvent is evaporated under reduced pressure to give a crude product which is purified by flash chromatography (gradient from isohexane to 47:3 isohexane:EtOAc) to give the titled compound as a white solid.
  • 6
  • [ 23218-93-1 ]
  • 3-amino-2,4,6-tribromo-5-nitro-benzoic acid methyl ester [ No CAS ]
  • 8
  • [ 23218-93-1 ]
  • [ 75-36-5 ]
  • [ 14622-17-4 ]
  • 9
  • [ 618-32-6 ]
  • [ 23218-93-1 ]
  • 3-benzoylamino-5-nitro-benzoic acid methyl ester [ No CAS ]
  • 3-Amino-5-nitro-benzoic acid methyl ester; hydrobromide [ No CAS ]
  • 10
  • [ 34549-54-7 ]
  • [ 23218-93-1 ]
  • 3-(3-Chloro-benzoylamino)-5-nitro-benzoic acid methyl ester [ No CAS ]
  • 3-Amino-5-nitro-benzoic acid methyl ester; hydrobromide [ No CAS ]
  • 11
  • [ 23218-93-1 ]
  • [ 13277-62-8 ]
  • 3-Nitro-5-(3-nitro-benzoylamino)-benzoic acid methyl ester [ No CAS ]
  • 3-Amino-5-nitro-benzoic acid methyl ester; hydrobromide [ No CAS ]
  • 14
  • [ 23218-93-1 ]
  • [ 49764-90-1 ]
  • 3-(3,5-Dimethyl-benzoylamino)-5-nitro-benzoic acid methyl ester [ No CAS ]
  • 3-Amino-5-nitro-benzoic acid methyl ester; hydrobromide [ No CAS ]
  • 15
  • [ 23218-93-1 ]
  • [ 100-39-0 ]
  • methyl 3-(benzylamino)-5-nitrobenzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
45.2% In N,N-dimethyl-formamide; at 120℃; for 0.333333h;Microwave irradiation; Example 77 methyl 3-(benzylamino)-5-((3-carbamoyl-7-(2,4-dimethoxypyrimidin-5-yl)quinolin-4 yl)amino)benzoate a) methyl 3-(benzylamino)-5-nitrobenzoate. To a solution of methyl 3-amino-5- nitrobenzoate (500 mg, 2.55 mmol) in N,N-dimethylformamide (5 ml.) was added (bromomethyl)benzene (436 mg, 2.55 mmol). The reaction was heated in a microwave reactor at 120 C for 20 minutes. After cooling, the organic solvent was removed under reduced pressure. The resulting oil was purified by flash chromagraphy (silica gel, 0-100% ethyl acetate in hexanes) to afford methyl 3- (benzylamino)-5-nitrobenzoate (330 mg, 1.153 mmol, 45.2 % yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) delta ppm 3.86 (s, 3 H) 4.41 (d, J=5.81 Hz, 2 H) 7.23 - 7.29 (m, 1 H) 7.33 - 7.40 (m, 5 H) 7.56 (d, J=1 .77 Hz, 2 H) 7.78 (t, J=1.77 Hz, 1 H). LCMS (ES+) m/e 287 [M+H]+.
45.2% In N,N-dimethyl-formamide; at 120℃; for 0.333333h;Microwave irradiation; a) methyl 3-(benzylamino)-5-nitrobenzoate. To a solution of methyl 3-amino-5- nitrobenzoate (500 mg, 2.55 mmol) in N,N-dimethylformamide (5 mL) was added (bromomethyl)benzene (436 mg, 2.55 mmol). The reaction was heated in a microwave reactor at 120 C for 20 minutes. After cooling, the organic solvent was removed under reduced pressure. The resulting oil was purified by flash chromagraphy (silica gel, 0-100% ethyl acetate in hexanes) to afford methyl 3- (benzylamino)-5-nitrobenzoate (330 mg, 1.153 mmol, 45.2 % yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) delta ppm 3.86 (s, 3 H) 4.41 (d, J=5.81 Hz, 2 H) 7.23 - 7.29 (m, 1 H) 7.33 - 7.40 (m, 5 H) 7.56 (d, J=1 .77 Hz, 2 H) 7.78 (t, J=1.77 Hz, 1 H). LCMS (ES+) m/e 287 [M+H]+.
  • 17
  • [ 23218-93-1 ]
  • [ 618-46-2 ]
  • 3-(3-Chloro-benzoylamino)-5-nitro-benzoic acid methyl ester [ No CAS ]
  • 3-Amino-5-nitro-benzoic acid methyl ester; hydrochloride [ No CAS ]
  • 18
  • [ 23218-93-1 ]
  • [ 98-88-4 ]
  • 3-benzoylamino-5-nitro-benzoic acid methyl ester [ No CAS ]
  • 3-Amino-5-nitro-benzoic acid methyl ester; hydrochloride [ No CAS ]
  • 19
  • [ 23218-93-1 ]
  • [ 100-07-2 ]
  • 3-Amino-5-nitro-benzoic acid methyl ester; hydrochloride [ No CAS ]
  • 3-(4-Methoxy-benzoylamino)-5-nitro-benzoic acid methyl ester [ No CAS ]
  • 21
  • [ 23218-93-1 ]
  • [ 766-80-3 ]
  • 3-(3-Chloro-benzylamino)-5-nitro-benzoic acid methyl ester [ No CAS ]
  • 22
  • [ 23218-93-1 ]
  • [ 6613-44-1 ]
  • 3-Amino-5-nitro-benzoic acid methyl ester; hydrochloride [ No CAS ]
  • 3-(3,5-Dimethyl-benzoylamino)-5-nitro-benzoic acid methyl ester [ No CAS ]
  • 24
  • [ 23218-93-1 ]
  • [ 28188-41-2 ]
  • 3-(3-Cyano-benzylamino)-5-nitro-benzoic acid methyl ester [ No CAS ]
  • 25
  • [ 23218-93-1 ]
  • [ 3958-57-4 ]
  • 3-Nitro-5-(3-nitro-benzylamino)-benzoic acid methyl ester [ No CAS ]
  • 27
  • [ 23218-93-1 ]
  • [ 121-90-4 ]
  • 3-Nitro-5-(3-nitro-benzoylamino)-benzoic acid methyl ester [ No CAS ]
  • 3-Amino-5-nitro-benzoic acid methyl ester; hydrochloride [ No CAS ]
  • 28
  • [ 23218-93-1 ]
  • [ 99-33-2 ]
  • 3-Amino-5-nitro-benzoic acid methyl ester; hydrochloride [ No CAS ]
  • 3-(3,5-Dinitro-benzoylamino)-5-nitro-benzoic acid methyl ester [ No CAS ]
  • 33
  • [ 7719-09-7 ]
  • [ 23218-93-1 ]
  • 3-nitro-5-sulfinylamino-benzoic acid methyl ester [ No CAS ]
  • 34
  • [ 23218-93-1 ]
  • [ 7726-95-6 ]
  • [ 64-19-7 ]
  • 3-amino-2,4,6-tribromo-5-nitro-benzoic acid methyl ester [ No CAS ]
  • 35
  • [ 23218-93-1 ]
  • [ 103-80-0 ]
  • [ 909401-93-0 ]
 

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