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Chemical Structure| 4743-17-3 Chemical Structure| 4743-17-3

Structure of 4743-17-3

Chemical Structure| 4743-17-3

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Product Details of [ 4743-17-3 ]

CAS No. :4743-17-3
Formula : C8H4ClNO3
M.W : 197.58
SMILES Code : ClC1=CC2=C(NC(=O)OC2=O)C=C1
MDL No. :MFCD00006701
InChI Key :MYQFJMYJVJRSGP-UHFFFAOYSA-N
Pubchem ID :78480

Safety of [ 4743-17-3 ]

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

Computational Chemistry of [ 4743-17-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 10
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 48.11
TPSA ?

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

63.07 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.19
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

1.65
Log Po/w (WLOGP)?

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

1.13
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.

1.59
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

2.71
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.66

Water Solubility

Log S (ESOL):?

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

-2.67
Solubility 0.419 mg/ml ; 0.00212 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.

-2.59
Solubility 0.51 mg/ml ; 0.00258 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

-3.77
Solubility 0.0339 mg/ml ; 0.000171 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

Yes
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.

-6.33 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

0.0 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)

2.48

Application In Synthesis of [ 4743-17-3 ]

* 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 [ 4743-17-3 ]

[ 4743-17-3 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 1192-07-0 ]
  • [ 4743-17-3 ]
  • [ 37795-70-3 ]
  • 2
  • [ 4743-17-3 ]
  • [ 2133-34-8 ]
  • [ 172410-92-3 ]
YieldReaction ConditionsOperation in experiment
In methanol; acetic acid; N,N-dimethyl-formamide; a) 59.3 g (0.3 mol) of 5-chloro-isatoic anhydride and 30.3 g (0.3 mol) of (S)-azetidine-2-carboxylic acid were suspended in 400 ml of N,N-dimethylformamide/acetic acid 5:1 and heated to 87-90 in an oil bath under argon for 64 hrs. The solvent was removed in a vacuum and the residue was taken up in 500 ml of methanol, whereupon the mixture was stirred at room temperature for 30 min. The white, pure crystals were filtered off under suction. The solvent was removed in a vacuum and the semi-crystalline residue was recrystallized from 60 ml of methanol (hot filtration). The products were combined and dried in a vacuum. There were obtained 61.3 g (86%) of (S)-6-chloro-1,2,4,9,10,10a-hexahydro-azeto[2,1-c][1,4]benzodiazepine-4,10-dione of m.p. 229-231 (dec.).
  • 3
  • [ 4743-17-3 ]
  • [ 2886-33-1 ]
  • 7-chloro-2,5-dioxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-3-acetic acid benzyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
19.8% With pyridine; at 120℃; for 18h; 5-chloroisatoic anhydride (compound 18) (1 g, 5.06 mmol) and <strong>[2886-33-1]L-aspartic acid dibenzyl ester p-toluenesulfonate salt</strong> (6) (2.98 g, 6.13 mmol) are suspended inpyridine (20 mE) to form a suspended solution, and the suspended solution is heated to 120C. and dissolved completely and reacted for 18 hours. After 18 hours, the reaction solution is cooled to room temperature, and drops of 6N HC1 are added gradually to acidiFy the reaction solution to a pH value approximately equal to 1. The acidified reaction solution is extracted by ethyl acetate (50 mEx3), and the combined organic layer is washed by saturated salt water, and then anhydrous magnesium sulfate is used for drying and filtering. The filtered solution is concentrated to obtain a crude product, and then the crude product is re-crystallized by ethyl acetate and water to obtain the final white solid product which is the compound 78 (0.36 g, 19.8%). Analysis Data of Compound 7B ?H-NMR (300 MHz, DMSO-d5): oe 2.80 (dd, 1H),2.95 (dd, 1H), 4.10 (ddd, 1H), 5.05 (s, 2H), 7.10 (d, 1H), 7.33 (m, 5H), 7.60 (dd, 1H), 7.70 (d, 1H), 8.76 (dd, 1H), 10.60 (s, NH); ?3C-NMR(75 MHz, DMSO-d5): oe 171.0, 170.3, 166.1, 136.4, 135.9, 132.7, 130.2, 129.0, 128.7, 128.4, 128.2, 128.1,121.6, 66.0, 49.0, 33.0
 

Historical Records

Technical Information

• Acyl Group Substitution • Alkyl Halide Occurrence • Baeyer-Villiger Oxidation • Barbier Coupling Reaction • Baylis-Hillman Reaction • Bouveault-Blanc Reduction • Bucherer-Bergs Reaction • Catalytic Hydrogenation • Chan-Lam Coupling Reaction • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Bakshi-Shibata (CBS) Reduction • Corey-Chaykovsky Reaction • Ester Cleavage • Fischer Indole Synthesis • General Reactivity • Grignard Reaction • Henry Nitroaldol Reaction • Hiyama Cross-Coupling Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Lawesson's Reagent • Leuckart-Wallach Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Peterson Olefination • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Amines • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions with Organometallic Reagents • Reformatsky Reaction • Robinson Annulation • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Specialized Acylation Reagents-Carbodiimides and Related Reagents • Specialized Acylation Reagents-Ketenes • Stille Coupling • Stobbe Condensation • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Tebbe Olefination • Ugi Reaction • Wittig Reaction • Wolff-Kishner Reduction

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