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Structure of 18583-89-6

Chemical Structure| 18583-89-6

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Product Details of [ 18583-89-6 ]

CAS No. :18583-89-6
Formula : C9H11NO2
M.W : 165.19
SMILES Code : O=C(OC)C1=CC=CC(N)=C1C
MDL No. :MFCD00211328
InChI Key :ZOOQFAUFPWXUMI-UHFFFAOYSA-N
Pubchem ID :3801025

Safety of [ 18583-89-6 ]

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

Computational Chemistry of [ 18583-89-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.22
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 47.09
TPSA ?

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

52.32 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.77
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

1.46
Log Po/w (WLOGP)?

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

1.37
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.

1.64
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

1.44
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.54

Water Solubility

Log S (ESOL):?

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

-2.02
Solubility 1.57 mg/ml ; 0.00951 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.

-2.16
Solubility 1.13 mg/ml ; 0.00684 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

-2.49
Solubility 0.531 mg/ml ; 0.00321 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

Yes
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.

-6.27 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

1.0 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)

1.32

Application In Synthesis of [ 18583-89-6 ]

* 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 [ 18583-89-6 ]

[ 18583-89-6 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 18583-89-6 ]
  • [ 192945-49-6 ]
YieldReaction ConditionsOperation in experiment
69% With acetic acid; sodium nitrite; In water; Methyl-3-amino-2-methyl benzoate (0.3 g, 1.96 mmol) was stirred in aqueous NaNO2 (0.62 g, 2 mmol) followed by addition of 7 mL dilute glacial acetic acid in water (7 mL, 3 mmol) (0.2:10). The reaction mixture was allowed to stir for 4-6 hrs. The mixture was then extracted with EtOAc and washed with water (2×10 mL). The organic layer was dried over Na2SO4, concentrated and subjected to column chromatography to obtain yellow powder. The yield was 0.22 g, 69%; m.p. 153-155 C. 1H NMR (400 MHz CDCl3, TMS, ppm) delta 2.55 (s, 3H), 7.37 (t, 1H, J=14.32 Hz), 7.53 (s, 1H), 7.67 (d, 1H, J=8.12 Hz), 7.82 (d, 1H, J=8.16 Hz), 9.79 (s, 1H).
59% Reference Example 1 methyl 1H-indazole-4-carboxylate A mixture of methyl 3-amino-o-toluate (100 g, 605 mmol), a solution of ammonium tetrafluoroborate (83.0 g, 787 mmol) in water (600 mL) and concentrated hydrochloric acid (121 mL, 3.93 mmol) was cooled to 0C, and a solution of sodium nitrite (41.8 g, 605 mmol) in water (88 mL) was added dropwise to the mixture over 25 min. This mixture was stirred for 35 min, and the resulting solid was collected by filtration. This solid was washed with water, methanol and diethyl ether, dried under nitrogen atmosphere, and added to a solution of potassium acetate (65.4 g, 666 mmol) and 18-crown-6 (4.50 g, 17.0 mmol) in chloroform (1.37 L). The resulting mixture was stirred at room temperature for 2 hr, and water (700 mL) was added. The partitioned organic layer was washed with water, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was triturated with hexane, and collected by filtration to give the title compound (63.0 g, yield 59%). 1H-NMR (CDCl3) delta: 4.03 (3H, s), 7.47 (1H, dd, 8.4, 7.2 Hz), 7.73 (1H, d, J = 8.4 Hz), 7.96 (1H, d, J = 7.2 Hz), 8.61 (1H, s), MS (ESI+): 177 (M+H).
Step 3: methyl 1 H-indazole-4-carboxylate; To a cold (0-5 C) solution of methyl-3-amino-2-methyl benzoate (16.6 mL, 19.0 g, 0.12 mol) in chloroform (200 mL) was added dropwise acetic anhydride (24.8 mL, 0.26 mol) followed by stirring for 5 minutes. The resulting mixture was allowed to warm to room temperature and stirred for 1 hour and then was added potassium acetate (3.35g, 0.034 mol) and isoamyl nitrite (33.0 mL, 0.25 mol) and heated under reflux for 20 hours. The mixture was cooled to room temperature and solvent was evaporated to yield a brown solid. Water was added to the solid, followed by evaporation to yield a solid residue. The residue was treated with concentrated hydrochloric acid and the resulting mixture was heated at 500C for 2 hours. After cooling with an ice bath, the solution was basified to pH 14 with a 50% potassium hydroxide solution. The resulting solid was collected by filtration, washed with water and dried to yield 17.8 g of methyl 1 H-indazole-4-carboxylate as a beige solid. MS: 177.0 [M+H].
  • 2
  • [ 628-36-4 ]
  • [ 18583-89-6 ]
  • C11H11N3O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With chloro-trimethyl-silane; triethylamine; In pyridine; at 100℃; Aniline (1.5 g, 9.1 mmol) was dissolved in pyridine (45 mL) and<strong>[628-36-4]diformylhydrazine</strong> (2.4 g, 27.2 mmol) was added as a single portion.Chlorotrimethylsilane (17.3 mL, 136.2 mmol) was added dropwise followed bytriethylamine (8.9 mL, 63.6 mmol) dropwise. The reaction as heated overnight to 100°C after which is was cooled to room temperature, diluted with EtOAc, washed with water, brine and dried over magnesium sulfate. Filtration and concentration was followed by silica gel chromatography (eluent: EtOAc / hexanes) to yield the product.
 

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