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Chemical Structure| 598-10-7 Chemical Structure| 598-10-7

Structure of 598-10-7

Chemical Structure| 598-10-7

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Product Details of [ 598-10-7 ]

CAS No. :598-10-7
Formula : C5H6O4
M.W : 130.10
SMILES Code : O=C(C1(C(O)=O)CC1)O
MDL No. :MFCD00013727
InChI Key :FDKLLWKMYAMLIF-UHFFFAOYSA-N
Pubchem ID :69017

Safety of [ 598-10-7 ]

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

Computational Chemistry of [ 598-10-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 0
Fraction Csp3 0.6
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 2.0
Molar Refractivity 27.32
TPSA ?

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

74.6 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.45
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

-0.17
Log Po/w (WLOGP)?

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

-0.13
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.

-0.52
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

-0.12
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.1

Water Solubility

Log S (ESOL):?

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

-0.41
Solubility 50.9 mg/ml ; 0.391 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.

-0.94
Solubility 14.9 mg/ml ; 0.114 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very 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

0.59
Solubility 507.0 mg/ml ; 3.9 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.

-7.21 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.

0.56

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)

1.18

Application In Synthesis of [ 598-10-7 ]

* 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 [ 598-10-7 ]

[ 598-10-7 ] Synthesis Path-Downstream   1~11

  • 1
  • [ 6914-79-0 ]
  • [ 598-10-7 ]
  • 2
  • [ 6914-79-0 ]
  • aqueous KOH-solution [ No CAS ]
  • [ 598-10-7 ]
  • 3
  • [ 6914-71-2 ]
  • [ 598-10-7 ]
  • [ 113020-21-6 ]
  • 4
  • [ 886762-08-9 ]
  • [ 598-10-7 ]
  • 1-([5-bromo-2-(trifluoromethoxy)phenyl]amino}carbonyl)cyclopropanecarboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
35% Under nitrogen conditions, 2.2mL dry triethylamine was added dropwise to 2g (15.4mmol) in methylene chloride solution of 1,1-cyclopropane dicarboxylic acid, the ice bath was stirred for 30min, then slowly dropping 1.2 mL SOCl2 methylene chloride solution. after the addition was complete stirring for 2h, the reaction mixture 71/92 3.5g (13.9mmol) 5- bromo-2-trifluoromethoxy aniline methylene chloride solution, and after the addition was complete stirring was continued for 2h. After completion of the reaction, the reaction mixture was 2mol / L NaOH solution was adjusted to pH 10, evaporated to dryness under reduced pressure, water was added q.s. ultrasonic, extracted once with ethyl acetate, the aqueous layer was retained, then 2mol / L HCl aqueous layer adjusted to pH 2, extracted three times with ethyl acetate, the organic solvent under reduced rotation, i.e., to give 1 - ([5-bromo-2- (trifluoromethoxy) phenyl] amino} carbonyl) cyclopropanecarboxylic acid acid, about 0.8g, 35% yield;
35% Under nitrogen atmosphere, 2.2 mL of anhydrous triethylamine was added dropwise to a solution of 2 g (15.4 mmol) of 1,1-cyclopropanedicarboxylic acid in dichloromethane, and the mixture was stirred for 30 min in an ice bath and then 1.2 mL SOCl2 in dichloromethane,After the addition was complete, the mixture was stirred for 2h, and then 3.5g (13.9mmol) of <strong>[886762-08-9]5-bromo-2-trifluoromethoxyaniline</strong> in dichloromethane was added dropwise to the reaction mixture. After the addition was completed, stirring was continued for 2h. The reaction solution was then adjusted to pH 10 with 2 mol / L NaOH solution, evaporated to dryness under reduced pressure, sonicated with appropriate amount of water, extracted once with ethyl acetate, the aqueous layer was retained,The aqueous layer was further adjusted to pH 2 with 2 mol / L HCl and extracted three times with ethyl acetate.The organic solvent was removed under reduced pressure to give 1 - ([5-bromo-2- (trifluoromethoxy) phenyl] amino} carbonyl) cyclopropanecarboxylic acid, About 0.8g, yield 35%;
General procedure: 1,1-Cyclopropanedicarboxylic acid (5) (12.0 g, 15.4 mmol) was dissolved in anhydrous THF (50 mL). Then triethanolamine (2.0 mL,13.9 mmol) was added to the mixture and the mixture was stirred on the ice-bath for 30 min. SOCl2 (1.2 mL, 16.66 mmol) was then added. Stirring was continued for 2h, a solution of 3,5-dimethylaniline 6 (3.6 g, 15.4 mmol) in anhydrous THF (10 mL) was added and continued stirring for 2h, after that, the ice bath was removed, and the mixture was stirred at room temperature overnight. After the completion of the reaction, the mixture was filtered and concentrated in vacuo. The residues was purified by silica gel flash chromatography (PE/AcOEt = 5:1) to yield 7 as white solid (0.8 g, 30.7%).
  • 5
  • [ 886762-08-9 ]
  • [ 598-10-7 ]
  • N-[4-(3-amino-1H-indazol-4-yl)phenyl]-N-[5-bromo-2-(trifluoromethoxy)phenyl]cyclopropane-1,1-dicarboxamide [ No CAS ]
  • 6
  • [ 175278-09-8 ]
  • [ 598-10-7 ]
  • C12H9BrF3NO4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: 1,1-Cyclopropanedicarboxylic acid (5) (12.0 g, 15.4 mmol) was dissolved in anhydrous THF (50 mL). Then triethanolamine (2.0 mL,13.9 mmol) was added to the mixture and the mixture was stirred on the ice-bath for 30 min. SOCl2 (1.2 mL, 16.66 mmol) was then added. Stirring was continued for 2h, a solution of 3,5-dimethylaniline 6 (3.6 g, 15.4 mmol) in anhydrous THF (10 mL) was added and continued stirring for 2h, after that, the ice bath was removed, and the mixture was stirred at room temperature overnight. After the completion of the reaction, the mixture was filtered and concentrated in vacuo. The residues was purified by silica gel flash chromatography (PE/AcOEt = 5:1) to yield 7 as white solid (0.8 g, 30.7%).
  • 7
  • [ 175278-09-8 ]
  • [ 598-10-7 ]
  • N-[4-(3-amino-1H-indazol-4-yl)phenyl]-N-[4-bromo-2-(trifluoromethoxy)phenyl]cyclopropane-1,1-dicarboxamide [ No CAS ]
  • 9
  • [ 175278-09-8 ]
  • [ 598-10-7 ]
  • N-(4-(2-aminoquinazolin-7-yl)phenyl)-N-(3-bromo-5-(trifluoromethoxy)phenyl)cyclopropane-1,1-dicarboxamide [ No CAS ]
  • 10
  • [ 886762-08-9 ]
  • [ 598-10-7 ]
  • N-(4-(2-aminoquinazolin-7-yl)phenyl)-N-(5-bromo-2-(trifluoromethoxy)phenyl)cyclopropane-1,1-dicarboxamide [ No CAS ]
  • 11
  • [ 67-56-1 ]
  • [ 598-10-7 ]
  • [ 6914-71-2 ]
 

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Technical Information

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[ 598-10-7 ]

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