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Structure of 18144-47-3

Chemical Structure| 18144-47-3

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Product Details of [ 18144-47-3 ]

CAS No. :18144-47-3
Formula : C11H15NO2
M.W : 193.24
SMILES Code : O=C(OC(C)(C)C)C1=CC=C(N)C=C1
MDL No. :MFCD00665790
InChI Key :KYORUZMJUKHKFS-UHFFFAOYSA-N
Pubchem ID :233272

Safety of [ 18144-47-3 ]

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

Computational Chemistry of [ 18144-47-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.36
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 56.58
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.

2.26
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

2.08
Log Po/w (WLOGP)?

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

2.23
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.

2.23
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

1.71
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.1

Water Solubility

Log S (ESOL):?

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

-2.47
Solubility 0.658 mg/ml ; 0.00341 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.

-2.81
Solubility 0.3 mg/ml ; 0.00155 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

-2.94
Solubility 0.221 mg/ml ; 0.00115 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.

-6.0 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)

1.39

Application In Synthesis of [ 18144-47-3 ]

* 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 [ 18144-47-3 ]

[ 18144-47-3 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 1120-95-2 ]
  • [ 18144-47-3 ]
  • C15H17N3O2 [ No CAS ]
  • 2
  • [ 464213-93-2 ]
  • [ 18144-47-3 ]
  • [ 37091-73-9 ]
  • [ 464215-46-1 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In dichloromethane; Example 188 tert-Butyl N-[5-(5,6-dimethoxy-3-methyl-1,4-benzoquinon-2-yl)methyl-2-acetoxybenzoyl]-4-aminobenzoate tert-Butyl 4-aminobenzoate (0.620 g, 6.209 mmol), triethylamine (0.325 g, 3.209 mmol) and <strong>[37091-73-9]2-chloro-1,3-dimethylimidazolinium chloride</strong> (0.542 g, 3.209 mmol) were added to a methylene chloride solution (150 ml) of 5-(5,6-dimethoxy-3-methyl-1,4-benzoquinon-2-yl)methyl-2-acetoxybenzoic acid (0.400 g, 1.070 mmol) and the resulting solution was stirred at room temperature for 6 hours. The reaction solution was poured into ice water and then extracted with methylene chloride. The extract was washed with water and then dried, and the solvent was removed by distillation. The obtained residue was purified by preparative thin-layer chromatography (ethyl acetate: hexane = 1:2-->1:0) to obtain the titled compound (0.302 g, 0.549 mmol, 57percent).
  • 3
  • [ 108-77-0 ]
  • [ 75-89-8 ]
  • [ 18144-47-3 ]
  • [ 42303-42-4 ]
  • [ 1287220-24-9 ]
YieldReaction ConditionsOperation in experiment
Step 1 : iPr2NEt (10 mL) was added into the solution of 2,4,6-trichloro-1,3,5-triazine (2.5 g) and 2,2,2-trifluoroethanol (1.36 g) in THF (100 mL). The reaction was stirred at room temperature for 16 hours before tert-butyl 4-aminobenzoate (2.62 g) was added. The resulting mixture was stirred at room temperature for 40 hours. Then, <strong>[42303-42-4]ethyl <strong>[42303-42-4]1-aminocyclopropanecarboxylate hydrochloride</strong></strong> (2.25 g) was added into the mixture. The reaction was carried out at r.t. for 16 hours, then 115 C. for 16 hours. The reaction was quenched with water. The aqueous layer was extracted with EtOAc (3×100 mL). The combined organic layer was dried over Mg2SO4 and concentrated to offer a residue which will be purified by silica gel chromatography.
Step 1 : iPr2NEt (10 mL) was added into the solution of 2,4,6-trichloro-l,3,5-triazine (2.5 g) and 2,2,2-trifluoroethanol (1.36 g) in THF (100 mL). The reaction was stirred at room temperature for 16 hours before tert-butyl 4-aminobenzoate (2.62 g) was added. The resulting mixture was stirred at room temperature for 40 hours. Then, ethyl 1 -aminocyclopropanecarboxylate hydrochloride (2.25 g) was added into the mixture. The reaction was carried out at r.t. for 16 hours, then 1 15C for 16 hours. The reaction was quenched with water. The aqueous layer was extracted with EtOAc (3 x lOOmL). The combined organic layer was dried over Mg2S04 and concentrated to offer a residue which will be purified by silica gel chromatography.
  • 4
  • [ 18144-47-3 ]
  • [ 42303-42-4 ]
  • [ 1287220-25-0 ]
  • 5
  • [ 81719-53-1 ]
  • [ 18144-47-3 ]
  • tert-butyl 4-(3,5-dichloropicolinamido)benzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃; Step 1 : tert-Butyl 4-(3,5-dichloropicolinamido)benzoate N,N-Diisopropylethylamine (5.46 ml, 31.3 mmol) was added to a stirred room temperature mixture of HATU (7.9 g, 20.8 mmol), tert-butyl-4-aminobenzoate 2.4 g (12.5 mmol), and 3,5- dichloropicolinic acid (2 g, 10.4 mmol) in DMF 30 ml. The mixture was stirred at room temperature overnight. The mixture was cooled and diluted with ethyl acetate. The organic phase was washed with aqueous sodium hydrogen carbonate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (Biotage 40M), eluting with ethyl acetate/isohexane to give tert-butyl 4-(3,5- dichloropicolinamido)benzoate a yellow solid. MS (ESI) m/z 367.19 (M+H).
  • 6
  • [ 1122-12-9 ]
  • [ 18144-47-3 ]
  • C15H13Br2NO4 [ No CAS ]
 

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