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Structure of 21724-96-9

Chemical Structure| 21724-96-9

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Product Details of [ 21724-96-9 ]

CAS No. :21724-96-9
Formula : C10H6BrNO2
M.W : 252.06
SMILES Code : O=C(C(C1=CC=C(Br)C=C1)=C2)NC2=O
MDL No. :MFCD19328381
InChI Key :YDIFCLVEBRJPOA-UHFFFAOYSA-N
Pubchem ID :19843468

Safety of [ 21724-96-9 ]

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

Computational Chemistry of [ 21724-96-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 58.85
TPSA ?

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

46.17 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.61
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

1.63
Log Po/w (WLOGP)?

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

1.11
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.

1.95
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

2.48
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.75

Water Solubility

Log S (ESOL):?

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

-2.68
Solubility 0.526 mg/ml ; 0.00209 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.

-2.21
Solubility 1.55 mg/ml ; 0.00613 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

-3.94
Solubility 0.0287 mg/ml ; 0.000114 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.

-6.68 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

0.0
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<0.0
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)

2.12

Application In Synthesis of [ 21724-96-9 ]

* 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 [ 21724-96-9 ]

[ 21724-96-9 ] Synthesis Path-Downstream   1~11

  • 1
  • [ 541-59-3 ]
  • [ 2028-85-5 ]
  • [ 21724-96-9 ]
YieldReaction ConditionsOperation in experiment
With sodium acetate; copper dichloride; In water; acetone; at 0 - 20℃;pH 3 - 3.5; Preparation 1: 3-(4-bromophenyl)-1H-pyrrole-2,5-dione (P1) A solution of hydrochloric acid (37percent, 27 ml.) in water (11 ml_) was added to 4-bromo aniline (15 g) at room temperature with vigorous stirring and the formed precipitate was allowed to stir for further 30 minutes. Temperature was reduced to 0 0C and a solution of sodium nitrite (6.60 g) in water (17 ml_) was added dropwise to the stirred suspension. At the end of diazotisation, a clear yellow solution was obtained. Maleimide (16.90 g) in acetone (70 mL) was added dropwise at 0 0C and then the pH of the solution was adjusted to 3-3.5 by adding sodium acetate. Copper (II) chloride (1.76 g) was added to the vigorously stirred mixture. The reaction mixture was allowed to stir at 0 0C for 1 h and overnight at room temperature. Acetone was removed in vacuo, the residue was filtered and dried overnight in vacuo to give the crude title compound (14.12 g) which was used without further purification.MS (mlz): 251 [M-H]".
  • 3
  • [ 541-59-3 ]
  • [ 106-40-1 ]
  • diazonium salt [ No CAS ]
  • [ 21724-96-9 ]
  • [ 101422-55-3 ]
  • 4
  • [ 21724-96-9 ]
  • (1R,5S/1S,5R)-1-(4-bromo-phenyl)-3-aza-bicyclo[3.1.0]hexane-2,4-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
Preparation 2: (1/?,5S/1S,5/?)-1-(4-bromophenyl)-3-azabicyclo[3.1.0]hexane-2,4- dione (P2) Milled potassium hydroxide (6.29 g) was added in small portions to a stirred solution of trimethylsulfoxonium iodide (24.66 g) in anhydrous DMSO (224 mL). The resulting mixture was allowed to stir at room temperature for 1.5 h then 3-(4-bromophenyl)-1 H-pyrrole-2,5- dione (P1 , 14.12 g) dissolved in DMSO (90 mL) was then added dropwise and the resulting mixture was allowed to stir at room temperature for 20 minutes. Reaction temperature was brought to 0 °C and aqueous saturated NH4CI (150 mL) was slowly added, followed by Et2O (200 mL). After separation of the two phases, the aqueous layer was repeatedly extracted with Et2O (3 x 100 mL). Combined organic layers were washed with brine and then dried over Na2SO4. Evaporation of the solvent gave the crude title compound (9.61 g) which was used without further purification.MS (mlz): 265.1 [M-H]".
  • 5
  • [ 541-59-3 ]
  • [ 106-40-1 ]
  • [ 21724-96-9 ]
YieldReaction ConditionsOperation in experiment
57% A solution of hydrochloric acid (37percent, 13 mL) in water (5.5 mL) was added to 4-bromoaniline (7.48 g, 43.52 mmol) at r.t. with vigorous stirring and the formed precipitate was allowed to stir for 30 min. The reaction mixture was cooled to 0 °C and a solution of sodium nitrite (3.30 g, 47.87 mmol) in water (9 mL) was added dropwise. At the end of diazotization, a clear yellow solution was obtained. Maleimide (8.45 g, 87.05 mmol) in acetone (35 mL) was added dropwise at 0 °C and then the pH of the solution was adjusted to 3-3.5 by adding sodium acetate. CuCl2 (0.88 g, 6.57 mmol) was added to the vigorously stirred mixture. The reaction mixture was stirred at 0 °C for Ih and overnight at r.t. After completion of the reaction as confirmed by TLC, solvents were removed in vacuo to afford the crude compound, which was purified by column chromatography (silica gel, 4: 6 EtOAc: Pet. ether) to afford the title compound as a yellow solid (5.8 g, 57percent). ESIMS (m/z): 252.3 (M+l)
57% Step 1: Preparation of 3-(4-bromophenyl)-1H-pyrrole-2,5-dioneA solution of hydrochloric acid (37percent, 13 mL) in water (5.5 mL) was added to 4-bromoaniline (7.48 g, 43.52 mmol) at r.t. with vigorous stirring and the formed precipitate was allowed to stir for 30 min. The reaction mixture was cooled to 0° C. and a solution of sodium nitrite (3.30 g, 47.87 mmol) in water (9 mL) was added dropwise. At the end of diazotization, a clear yellow solution was obtained. Maleimide (8.45 g, 87.05 mmol) in acetone (35 mL) was added dropwise at 0° C. and then the pH of the solution was adjusted to 3-3.5 by adding sodium acetate. CuCl2 (0.88 g, 6.57 mmol) was added to the vigorously stirred mixture. The reaction mixture was stirred at 0° C. for 1 h and overnight at r.t. After completion of the reaction as confirmed by TLC, solvents were removed in vacuo to afford the crude compound, which was purified by column chromatography (silica gel, 4:6 EtOAc:Pet. ether) to afford the title compound as a yellow solid (5.8 g, 57percent).ESIMS (m/z): 252.3 (M+1)
  • 6
  • [ 623-73-4 ]
  • [ 21724-96-9 ]
  • [ 1259556-38-1 ]
YieldReaction ConditionsOperation in experiment
57% In toluene; for 18h;Reflux; To a solution of 3-(4-bromophenyl)-lH-pyrrole-2,5-dione (3.45 g, 13.74 mmol) obtained in Step 1 of Intermediate IX, in toluene (50 mL) was added ethyldiazoacetate (4.27 mL, 41.23 mmol). The reaction mixture was heated to reflux for 18h. After completion of the reaction as confirmed by TLC, solvent was removed in vacuo to afford crude product which was purified by column chromatography (silica gel, 4: 6 EtOAc: Pet. ether) to afford the title compound as a yellow solid (2.66 g, 57percent).ESIMS (m/z): 338.7(M+1)
57% In toluene; for 18h;Reflux; Step 2: Preparation of ethyl 1-(4-bromophenyl)-2,4-dioxo-3-aza-bicyclo[3.1.0]hexane-6-carboxylateTo a solution of <strong>[21724-96-9]3-(4-bromophenyl)-1H-pyrrole-2,5-dione</strong> (3.45 g, 13.74 mmol) obtained in Step 1 of Intermediate IX, in toluene (50 mL) was added ethyldiazoacetate (4.27 mL, 41.23 mmol). The reaction mixture was heated to reflux for 18 h. After completion of the reaction as confirmed by TLC, solvent was removed in vacuo to afford crude product which was purified by column chromatography (silica gel, 4:6 EtOAc:Pet. ether) to afford the title compound as a yellow solid (2.66 g, 57percent).ESIMS (m/z): 338.7 (M+1)
  • 7
  • [ 21724-96-9 ]
  • [ 1259556-66-5 ]
  • 8
  • [ 21724-96-9 ]
  • [ 1259556-39-2 ]
  • 9
  • [ 21724-96-9 ]
  • [ 1259556-40-5 ]
  • 10
  • [ 21724-96-9 ]
  • [ 1259556-41-6 ]
  • 11
  • [ 21724-96-9 ]
  • C10H8BrNO2 [ No CAS ]
 

Historical Records

Technical Information

• Acyl Group Substitution • Alkyl Halide Occurrence • Baeyer-Villiger Oxidation • Barbier Coupling Reaction • Baylis-Hillman Reaction • Bucherer-Bergs Reaction • Chan-Lam Coupling Reaction • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Bakshi-Shibata (CBS) Reduction • Corey-Chaykovsky Reaction • 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 of Benzene and Substituted Benzenes • Reactions of Dihalides • 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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