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Chemical Structure| 111296-91-4 Chemical Structure| 111296-91-4

Structure of 111296-91-4

Chemical Structure| 111296-91-4

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Product Details of [ 111296-91-4 ]

CAS No. :111296-91-4
Formula : C18H12N2
M.W : 256.30
SMILES Code : N1C2=CC=CC=C2C2=C1C=CC1=C2NC2=CC=CC=C12
MDL No. :MFCD22200776
InChI Key :QQWXDAWSMPLECU-UHFFFAOYSA-N
Pubchem ID :4713445

Safety of [ 111296-91-4 ]

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

Computational Chemistry of [ 111296-91-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 20
Num. arom. heavy atoms 20
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 0.0
Num. H-bond donors 2.0
Molar Refractivity 85.17
TPSA ?

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

31.58 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.13
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

4.85
Log Po/w (WLOGP)?

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

4.96
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.

3.63
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

5.12
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

4.14

Water Solubility

Log S (ESOL):?

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

-5.22
Solubility 0.00153 mg/ml ; 0.00000596 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-5.25
Solubility 0.00145 mg/ml ; 0.00000566 mol/l
Class?

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

Moderately 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

-7.52
Solubility 0.00000767 mg/ml ; 0.0000000299 mol/l
Class?

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

Poorly 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

Yes
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

Yes
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

Yes
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-4.42 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

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)

1.5

Application In Synthesis of [ 111296-91-4 ]

* 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 [ 111296-91-4 ]

[ 111296-91-4 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 3616-56-6 ]
  • [ 27393-85-7 ]
  • [ 111296-91-4 ]
YieldReaction ConditionsOperation in experiment
67% With acetic acid; at 118℃; for 8h;Inert atmosphere; Under a nitrogen atmosphere, 14.1 g (0.061 mol) of the intermediate A, 11.4 g (0.071 mol) ofN,N'-<strong>[3616-56-6]dimethylaminoacetaldehyde diethyl acetal</strong>, and 110.0 g of acetic acid were stirred for 8 hours while being heated at 118°C to reflux. After the reaction solution was cooled to room temperature, the precipitated crystal was collected by filtration and washed with acetic acid (30 ml) . The resultant crystal was subjected to purification by reslurrying to afford 10.4 g (67percent yield) of IC-2 as a white crystal.
67% With acetic acid; at 118℃; for 8h;Inert atmosphere; Under a nitrogen atmosphere, 14.1 g (0.061 mol) of Intermediate C, 11.4 g (0.071 mol) of N,N?-<strong>[3616-56-6]dimethylaminoacetaldehyde diethyl acetal</strong>, and 110.0 g of acetic acid were stirred for 8 hr while being refluxed under heat at 118° C. After the reaction solution had been cooled to room temperature, the precipitated crystal was taken by filtration and washed with acetic acid (30 ml). The resultant crystal was subjected to re-slurry purification to provide 10.4 g (0.041 mol, yield: 67percent) of 5,12-dihydroindolo[3,2-a]carbazole (IC-5) as a white crystal.
60% With acetic acid; at 130℃;Inert atmosphere; (3) 1H,1'H-2,3'-biindole (16.4 g, 70.6 mmol) and 2,2-diethoxy-N,N-dimethylethanamine (14.18 ml, 78 mmol) in glacial acetic acid (160 mL) were refluxed at 130 °C overnight under nitrogen. The reaction solution was cooled to room temperature and filtered. The filtrate was washed with small amount of acetic acid and excess of water. The filtrate was dried in the oven at 65°C overnight affording 10.79 g (60percent) of the 5,12-dihydroindolo[3,2-a]carbazole as gray solid.
  • 2
  • [ 26608-06-0 ]
  • [ 111296-91-4 ]
  • 5-(dibenzo[b,d]furan-3-yl)-5,12-dihydroindolo[3,2-a]carbazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
64% With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); XPhos; In toluene; for 12h;Inert atmosphere; Reflux; 10138] A solution of 5,12-dihydroindolo[3,2-a]carbazole (6 g, 23.41 mmol), <strong>[26608-06-0]3-bromodibenzo[b,d]furan</strong> (6.94 g, 28.1 mmol), Pd2(dba)3 (0.21 g, 0.23 mmol), Xphos (0.23 g, 0.47 mmol) and K3P04 (9.94 g, 46.8 mmol) in toluene (100 ml) was refluxed under nitrogen for 12 h. After cooling to room temperature, the solvent was evaporated and the residue was purified by column chromatography on silica gel with heptane/dichloromethane (1/1, v/v) as eluent to yield 5-(dibenzo [b,d]furan-3-yl)-5, 1 2-dihydroindolo[3,2-a]carbazole (6.3 g, 64%) as a white solid.
  • 3
  • [ 26608-06-0 ]
  • [ 111296-91-4 ]
  • C42H24N2O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
69% With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; In 5,5-dimethyl-1,3-cyclohexadiene; for 16h;Inert atmosphere; Reflux; 10141] A solution of 5,12-dihydroindolo[3,2-a]carbazole(2.86 g, 11.16 mmol), <strong>[26608-06-0]3-bromodibenzo[b,d]furan</strong> (6.20 g,25.1 mmol), Pd2(dba)3 (0.20 g, 0.22 mmol), SPhos (0.18 g,0.45 mmol) and tert-8uONa (4.29 g, 44.6 mmol) in xylene(120 ml) was refluxed under nitrogen for 16 h. The solvent was evaporated and the residue was purified by colunm chromatography on silica gel with heptane/dichloromethane (1/1, v/v) as eluent and recrystallized from the same solvent to yield Compound 819 (4.5 g, 69%) as white crystals.
  • 4
  • [ 111296-91-4 ]
  • [ 13438-50-1 ]
  • C34H20N2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In 5,5-dimethyl-1,3-cyclohexadiene;Inert atmosphere; Reflux; In a 250 mL three-necked flask, Compound A (1.0 g, 3.9 mmol), Compound B (1.2 g, 4.8 mmol), Pd2 (dba) 3 (0.04 g, 0.039 mmol), sodium t-butoxide (0.75 g. 7.8 mmol) were added. Tri-tert-butylphosphine tetrafluoroborate (0.02g,0.078mmol) and 30ml of xylene, pumping nitrogen three times, heating to reflux temperature under nitrogen protection, cooling after overnight reactionAfter room temperature, it was diluted with toluene, passed through a silica gel column, and then recrystallized from toluene to give a yellow solid (1.4 g, yield: 80percent).
  • 5
  • [ 111296-91-4 ]
  • [ 1097884-37-1 ]
  • C36H23N3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In toluene; at 95℃; for 24h; Intermediate 1-3 (10.0 g, 0.031 mol) to intermediate 1-5 (7.9 g, 0.031 mol),Pd (pph3) 4 (1.8 g, 0.0015 mol / P & H TECH),400 ml of TOL was added to potassium carbonate (12.8 g, 0.0935 mol / sigma aldrich) and reacted at 95 C. for 24 hours.After the completion of the reaction, the mixture was cooled and separated by H20: MC, followed by column purification (n-Hexane: MC), to obtain 12.6 g (yield 82%) of intermediate 1-6.
 

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