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Chemical Structure| 3297-72-1 Chemical Structure| 3297-72-1

Structure of 3297-72-1

Chemical Structure| 3297-72-1

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Product Details of [ 3297-72-1 ]

CAS No. :3297-72-1
Formula : C15H11N
M.W : 205.25
SMILES Code : C1(C2=CC=CC=C2)=NC=CC3=C1C=CC=C3
MDL No. :MFCD00093934
InChI Key :LPCWDYWZIWDTCV-UHFFFAOYSA-N
Pubchem ID :137882

Safety of [ 3297-72-1 ]

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

Computational Chemistry of [ 3297-72-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 16
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 67.18
TPSA ?

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

12.89 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.41
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

3.76
Log Po/w (WLOGP)?

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

3.9
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.

3.01
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

4.07
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.43

Water Solubility

Log S (ESOL):?

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

-4.16
Solubility 0.0144 mg/ml ; 0.0000699 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.

-3.72
Solubility 0.0388 mg/ml ; 0.000189 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

-6.22
Solubility 0.000123 mg/ml ; 0.000000598 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

Yes
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

No
Log Kp (skin permeation)?

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

-4.88 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<2.0
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)

1.71

Application In Synthesis of [ 3297-72-1 ]

* 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 [ 3297-72-1 ]

[ 3297-72-1 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 1532-71-4 ]
  • [ 108-86-1 ]
  • [ 3297-72-1 ]
  • 2
  • [ 1532-71-4 ]
  • [ 98-80-6 ]
  • [ 3297-72-1 ]
YieldReaction ConditionsOperation in experiment
96% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; at 80℃; for 24h; Place 2-<strong>[1532-71-4]bromoisoquinoline</strong> (20 g, 1 eq) in a dry 1000 ml two-necked flask.Phenylboronic acid (12.3 g, 1.05 eq), Pd (PPh3) 4 (5.55 g, 0.05 eq)And sodium carbonate (30.5 g, 3 eq), then dioxane (500 mL),The reaction was heated to 80 C and stirred for one day.Then, the reaction solution was spun dry, separated into water and dichloromethane, and the organic phase was dried.Purification by column to obtain white intermediate C(Yield 96%).
79% With potassium phosphate; In ethanol; water; at 100℃; for 8h; General procedure: A dried round bottomed flask equipped with a magnetic stirring bar was charged with 10mg Polymer anchored-Pd(II) D catalyst (PS-NPPZ-Pd) (0.0045mmol/Pd), 2-halopyridine (0.5mmol), phenylboronic acid (0.6mmol) and K3PO4 (1.0mmol) were added to a reaction vessel. The mixture was stirred in 4mL of H2O: EtOH (1:1) at 100C for 8h and then cooled to room temperature. The catalyst was filtered and the filtrate was extracted with ethyl acetate (3×10mL). The combined organic layers were extracted with water, and dried over anhydrous Na2SO4. The organic layers were evaporated under reduced pressure and the resulting crude product was purified by column chromatography by using ethyl acetate/hexane (10:90) as eluent to give the corresponding coupled products. The products were characterized by 1H NMR, 13C NMR and HRMS analysis.
  • 3
  • [ 1532-71-4 ]
  • [ 71-43-2 ]
  • [ 3297-72-1 ]
YieldReaction ConditionsOperation in experiment
55% With 8-quinolinol; potassium tert-butylate; at 80℃;Schlenk technique; Green chemistry; General procedure: The substituted aryl bromide (1.0 mmol), 8-hydroxyquinoline (20 molpercent) and KOtBu (2.0 mmol) were loaded into a Schlenk tube equipped with a Teflon-coated magnetic stir bar. The unactivated arene (8.0 mL or 80 equiv) was then added and the mixture was stirred at r.t. for 3?5 min. The Schlenk tube was placed in a preheated oil bath at 80 °C and the mixture was stirred for 18 h. After completion of the reaction as judged by GC analysis, the Schlenk tube was allowed to cool to r.t. and the contents quenched with H2O and diluted with EtOAc. The organic layer was separated, and the aqueous layer was extracted with EtOAc. The combined organic layer was dried over Na2SO4 and concentrated under reduced pressure. The crude residue was purified by flash column chromatography on silica gel to afford the desired biaryl product.
  • 4
  • [ 1008-89-5 ]
  • [ 3297-72-1 ]
  • iridium nitrate [ No CAS ]
  • [ 94928-86-6 ]
  • 1-phenylisoquinoline-bis(phenylpyridine) iridium [ No CAS ]
YieldReaction ConditionsOperation in experiment
84.1%Chromat.; 15.2%Chromat. In water; ethylene glycol; at 180℃; for 17h;Inert atmosphere; 403.8 mg of an iridium nitrate aqueous solution (iridium content: 9.52 wt percent), 93.1 mg of compound (A), 123.2 mg of compound (D) and 5 ml of ethylene glycol were reacted by heating in an argon atmosphere at 180° C. for 17 hours. The reaction mixture was cooled to room temperature, and methanol was added. The precipitated solid was collected by filtration, and washed with methanol. The yield of the resulting solid was 102 mg. Analysis was performed by HPLC (Prominence manufactured by Shimadzu Corporation, column: normal phase silica gel, mobile phase: mixed solvent of THF (40percent) and hexane (60percent), detection wavelength: 300 nm), and the result showed that the production ratios of compounds (1), (34) and (35) were 84.1percent, 15.2percent and 0.7percent (peak area ratio), respectively.
 

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