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Chemical Structure| 74450-59-2 Chemical Structure| 74450-59-2

Structure of 74450-59-2

Chemical Structure| 74450-59-2

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Product Details of [ 74450-59-2 ]

CAS No. :74450-59-2
Formula : C10H13NO2
M.W : 179.22
SMILES Code : O=C(OCC)C1=CC=C(N)C=C1C
MDL No. :MFCD08458830
Boiling Point : No data available
InChI Key :RXVUWRNRNRPYMT-UHFFFAOYSA-N
Pubchem ID :24721080

Safety of [ 74450-59-2 ]

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

Computational Chemistry of [ 74450-59-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.3
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 51.9
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.

2.03
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

1.83
Log Po/w (WLOGP)?

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

1.76
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.

1.94
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

1.8
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.87

Water Solubility

Log S (ESOL):?

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

-2.25
Solubility 1.01 mg/ml ; 0.00565 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.

-2.55
Solubility 0.506 mg/ml ; 0.00283 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

-2.9
Solubility 0.223 mg/ml ; 0.00124 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.

-6.09 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)

1.54

Application In Synthesis of [ 74450-59-2 ]

* 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 [ 74450-59-2 ]

[ 74450-59-2 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 62621-10-7 ]
  • [ 74450-59-2 ]
YieldReaction ConditionsOperation in experiment
93.94% With hydrogen;nickel; In methanol; under 2585.81 Torr; for 2.0h; Compound of example la (41g; 196 mmol) in MeOH (500 ml) was hydrogenated using Raney Ni (2g) at 50 psi for 2h. The solution was filtered free off the catalyst, concentrated and purified using flash chromatography (silica gel, 10% EtOAc-PE 60-80C, 30% EtOAc-PE 60- 80C) to obtain the title compound. Yield, 33g (93.94%) ; mp, 77-80C, MS (EI) : 179 (M+), 134 (100%), 106,77 ; analysis: C10H13NO2 requires, C, 67.02 ; H, 7.31 ; N, 7.82 ; found, C, 67.25 ; H, 7.26 ; N, 7.57%.
93.94% With hydrogen;Raney Ni; In methanol; under 2585.81 Torr; for 2.0h; Example 1b 4-Amino-2-methyl-benzoic acid ethyl ester Compound of example 1a (41 g; 196 mmol) in MeOH (500 ml) was hydrogenated using Raney Ni (2 g) at 50 psi for 2 h. The solution was filtered free off the catalyst, concentrated and purified using flash chromatography (silica gel, 10% EtOAc-PE 60-80 C., 30% EtOAc-PE 60-80 C.) to obtain the title compound. Yield, 33 g (93.94%); mp, 77-80 C., MS (EI): 179 (M+), 134 (100%), 106, 77; analysis: C10H13NO2 requires, C, 67.02; H, 7.31; N, 7.82; found, C, 67.25; H, 7.26; N, 7.57%.
  • 2
  • [ 74450-59-2 ]
  • C10H11N2O2(1+)*Cl(1-) [ No CAS ]
YieldReaction ConditionsOperation in experiment
Compound of example lb (32g; 178 mmol) was treated with conc. HCl (64 ml) and water (320 ml), cooled to 0C, then treated to a dropwise addition of an aqueous solution of NaNO2 (12.33g ; 178 mmol, 320 ml) over a period of lh at 0-5C. The diazonium salt solution was neutralized with Na2CO3 and added slowly to an aqueous solution of KCN and CuCN (13. 38g ; 204.4 mmol, 19.34g ; 204.4 mmol, 500 ml), maintained at 0-5C, with vigorous stirring over a period of 1h. The reaction mixture was stirred for 30 min. at 0-5C and left stirring overnight at room temperature. It was subsequently heated on steam bath for 30 min. , treated with an aqueous 10% Fecal3 solution and extracted with EtOAc (3x500 ml). The organic layer was washed with water, brine, dried (Na2SO4), concentrated, purified using flash chromatography (silica gel, 5% EtOAc-PE 60-80C) and crystallized using EtOAc-PE 60-80C to obtain the title compound as a pure white solid. Yield, 20g (59.2%) ; mp, 64-65C ; MS (EI) : 189 (M+), 144 (100%), 116,89 ; analysis: CIlHllNO2, 0.5 H20 requires C, 66.70 ; H, 6.06 ; N, 7.07 ; found: C, 67.11 ; H, 5. 88 ; N, 6.88%.
  • 3
  • potassium cyanide [ No CAS ]
  • [ 74450-59-2 ]
  • copper(l) cyanide [ No CAS ]
  • [ 220389-17-3 ]
YieldReaction ConditionsOperation in experiment
Example 1c 4-Cyano-2-methyl-benzoic acid ethyl ester Compound of example 1b (32 g; 178 mmol) was treated with conc. HCl (64 ml) and water (320 ml), cooled to 0 C., then treated to a dropwise addition of an aqueous solution of NaNO2 (12.33 g; 178 mmol, 320 ml) over a period of 1 h at 0-5 C. The diazonium salt solution was neutralized with Na2CO3 and added slowly to an aqueous solution of KCN and CuCN (13.38 g; 204.4 mmol, 19.34 g; 204.4 mmol, 500 ml), maintained at 0-5 C., with vigorous stirring over a period of 1 h. The reaction mixture was stirred for 30 min. at 0-5 C. and left stirring overnight at room temperature. It was subsequently heated on steam bath for 30 min., treated with an aqueous 10% FeCl3 solution and extracted with EtOAc (3*500 ml). The organic layer was washed with water, brine, dried (Na2SO4), concentrated, purified using flash chromatography (silica gel, 5% EtOAc-PE 60-80 C.) and crystallized using EtOAc-PE 60-80 C. to obtain the title compound as a pure white solid. Yield, 20 g (59.2%); mp, 64-65 C.; MS (EI): 189 (M+), 144 (100%), 116, 89; analysis: C11H11NO2, 0.5H2O requires C, 66.70; H, 6.06; N, 7.07; found: C, 67.11; H, 5.88; N, 6.88%.
 

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