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Chemical Structure| 52562-19-3 Chemical Structure| 52562-19-3

Structure of 52562-19-3

Chemical Structure| 52562-19-3

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Product Details of [ 52562-19-3 ]

CAS No. :52562-19-3
Formula : C9H11N
M.W : 133.19
SMILES Code : NC1=CC=CC=C1C(C)=C
MDL No. :MFCD00007719
InChI Key :HEDYZFYQYPWWCC-UHFFFAOYSA-N
Pubchem ID :96494

Safety of [ 52562-19-3 ]

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

Computational Chemistry of [ 52562-19-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.11
Num. rotatable bonds 1
Num. H-bond acceptors 0.0
Num. H-bond donors 1.0
Molar Refractivity 45.74
TPSA ?

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

26.02 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.92
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

2.64
Log Po/w (WLOGP)?

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

2.31
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.

2.37
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

2.08
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.26

Water Solubility

Log S (ESOL):?

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

-2.71
Solubility 0.262 mg/ml ; 0.00196 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.

-2.84
Solubility 0.194 mg/ml ; 0.00145 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

-2.84
Solubility 0.194 mg/ml ; 0.00146 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.

-5.24 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

2.0
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<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)

1.11

Application In Synthesis of [ 52562-19-3 ]

* 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 [ 52562-19-3 ]

[ 52562-19-3 ] Synthesis Path-Downstream   1~35

  • 2
  • [ 52562-19-3 ]
  • [ 79-03-8 ]
  • [ 119449-51-3 ]
  • 4
  • [ 52562-19-3 ]
  • [ 100-52-7 ]
  • (E)-1-phenyl-N-(2-(prop-1-en-2-yl)phenyl)methanimine [ No CAS ]
  • 5
  • [ 52562-19-3 ]
  • [ 98-88-4 ]
  • [ 106012-41-3 ]
YieldReaction ConditionsOperation in experiment
99% With triethylamine; In dichloromethane; for 1h;Cooling with ice; 1: In a 100 mL three-necked flask, add methyl triphenylphosphonium bromide (5.36 g, 15 mmol) and dry THF 20 mL. Under the protection of argon, potassium tert-butoxide (1.68g, 15mmol) was added to the reaction flask in batches under ice bath, and after the addition, the reaction was carried out at room temperature for 30min. Then o-aminoacetophenone (1.21 g, 10 mmol) was added, and the reaction was carried out overnight. After the reaction was completed, saturated sodium bicarbonate was added, and the mixture was extracted with ethyl acetate. After the extract was concentrated, silica gel column chromatography was performed to obtain the corresponding o-propenylaniline (0.88 g, yield=74%). In a 100 mL single-neck flask, o-propenyl aniline (0.99 g, 7.4 mmol) and triethylamine (1.53 g, 11.1 mmol) were dissolved in 15 mL of dichloromethane. Under an ice bath, a dichloromethane solution of benzoyl chloride (1.0 mL, 8.9 mmol) was slowly added dropwise. The reaction was completed in about 1 hour. After silica gel column chromatography, the corresponding amide (3.89 g, yield=99%) was obtained. In a 100mL three-neck flask, add NaH (640mg, 60%wt, 16mmol), replace the gas in the flask with argon three times, add 15mL of dry THF, and add dropwise the THF solution with amide (700mg, 4mmol) dissolved in it. Reaction at 60C for 2h. Then, nitrile bromide was added to the reaction solution and moved to room temperature overnight. The reaction solution was suction filtered, and the filtrate was concentrated and subjected to silica gel column chromatography to obtain the target product 1 (448 mg). White solid, 56% yield
  • 9
  • [ 52562-19-3 ]
  • [ 122-04-3 ]
  • 4-nitro-N-(2-(prop-1-en-2-yl)phenyl)benzamide [ No CAS ]
  • 10
  • [ 52562-19-3 ]
  • [ 142-61-0 ]
  • [ 119449-52-4 ]
  • 11
  • [ 52562-19-3 ]
  • [ 98-59-9 ]
  • [ 106745-67-9 ]
YieldReaction ConditionsOperation in experiment
With pyridine; In dichloromethane; at 20℃; for 24h; General procedure: The aniline (0.5 g, 3.75 mmol, 1 equiv) was dissolved in dry CH2Cl2 (7.5 mL, 0.5 M), and thesolution was treated with sulfonyl chloride (0.79 g, 4.13 mmol, 1.1 equiv) and pyridine (0.91mL, 11.3 mmol, 3 equiv). The mixture was stirred at room temperature for 24 h, diluted withH2O (25 mL) and extracted with CH2Cl2 (3 x 25 mL). The combined organic layers were washedwith 1M HCl, brine, dried over Na2SO4, and concentrated in vacuo. Flash chromatography of theresulting crude mixture on SiO2 (0-30% EtOAc in hexanes gradient) afforded the sulfonamidesin good yields. Substrate 1b was synthesized according to the above procedure using <strong>[52562-19-3]2-isopropenylaniline</strong> and 2-(trimethylsilyl)ethanesulfonyl chloride. Sulfonamide 1b was obtained
  • 16
  • [ 52562-19-3 ]
  • [ 108-94-1 ]
  • C15H19N [ No CAS ]
  • 17
  • [ 52562-19-3 ]
  • [ 98-53-3 ]
  • C19H27N [ No CAS ]
  • 22
  • [ 52562-19-3 ]
  • [ 100-39-0 ]
  • [ 490035-95-5 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In acetonitrile; at 90℃; General procedure: To a solution of SI-6 (1 equiv) in MeCN was added K2CO3(2 equiv) at room temperature, followed by a solution of BnBr (1 equiv) inMeCN. The reaction mixture was heated to 90oC and stirred overnight.After cooling to rt, the reaction was quenched with water. The aqueous layerwas extracted by EA and the combined organic layers were dried over MgSO4.After removing the solvent, the residue was purified by column chromatograph toobtain SI-7
  • 24
  • [ 52562-19-3 ]
  • [ 98-74-8 ]
  • [ 918297-95-7 ]
YieldReaction ConditionsOperation in experiment
99% With pyridine; In dichloromethane; at 20℃; for 24h; General procedure: The aniline (0.5 g, 3.75 mmol, 1 equiv) was dissolved in dry CH2Cl2 (7.5 mL, 0.5 M), and thesolution was treated with sulfonyl chloride (0.79 g, 4.13 mmol, 1.1 equiv) and pyridine (0.91mL, 11.3 mmol, 3 equiv). The mixture was stirred at room temperature for 24 h, diluted withH2O (25 mL) and extracted with CH2Cl2 (3 x 25 mL). The combined organic layers were washedwith 1M HCl, brine, dried over Na2SO4, and concentrated in vacuo. Flash chromatography of theresulting crude mixture on SiO2 (0-30% EtOAc in hexanes gradient) afforded the sulfonamidesin good yields. Substrate 1b was synthesized according to the above procedure using <strong>[52562-19-3]2-isopropenylaniline</strong> and 2-(trimethylsilyl)ethanesulfonyl chloride. Sulfonamide 1b was obtained
  • 25
  • [ 52562-19-3 ]
  • [ 124-63-0 ]
  • [ 918297-94-6 ]
YieldReaction ConditionsOperation in experiment
99% With pyridine; In dichloromethane; at 20℃; for 24h; General procedure: The aniline (0.5 g, 3.75 mmol, 1 equiv) was dissolved in dry CH2Cl2 (7.5 mL, 0.5 M), and thesolution was treated with sulfonyl chloride (0.79 g, 4.13 mmol, 1.1 equiv) and pyridine (0.91mL, 11.3 mmol, 3 equiv). The mixture was stirred at room temperature for 24 h, diluted withH2O (25 mL) and extracted with CH2Cl2 (3 x 25 mL). The combined organic layers were washedwith 1M HCl, brine, dried over Na2SO4, and concentrated in vacuo. Flash chromatography of theresulting crude mixture on SiO2 (0-30% EtOAc in hexanes gradient) afforded the sulfonamidesin good yields. Substrate 1b was synthesized according to the above procedure using <strong>[52562-19-3]2-isopropenylaniline</strong> and 2-(trimethylsilyl)ethanesulfonyl chloride. Sulfonamide 1b was obtained
  • 26
  • [ 201230-82-2 ]
  • [ 52562-19-3 ]
  • [ 19343-78-3 ]
  • 27
  • [ 201230-82-2 ]
  • [ 52562-19-3 ]
  • [ 19343-78-3 ]
  • [ 643-28-7 ]
  • 28
  • [ 52562-19-3 ]
  • [ 14722-38-4 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; sodium nitrite; In hydrogenchloride; EXAMPLE 1 4-(hydroxyiminomethyl)cinnoline hydrochloride (1) and 4-(hydroxyiminomethyl)cinnoline (2) A solution of 50.0 g of <strong>[52562-19-3]o-isopropenylaniline</strong> (Aldrich) in 440 ml of 2N hydrochloric acid was treated with 86 ml of 12N hydrochloric acid at 20 C. The resulting mixture was extracted with ether to remove a small amount of an insoluble oil. The aqueous phase was cooled to 0 C. and treated with 24.5 g of sodium nitrite, in portions, over 2 hours, at 0-5 C. The resulting mixture was stirred for 30 minutes at 0 C., warmed to room temperature, heated to 60 C., held at room temperature over a weekend, neutralized with sodium bicarbonate, made basic with 50% sodium hydroxide solution, and extracted with ether. The extract was washed with brine, dried (MgSO4), charcoaled, filtered and stripped of solvent. The residue was recrystallized from hexane to give 4-methylcinnoline (1A), as a solid, m.p.: 70-72 C.
With sodium hydroxide; sodium nitrite; In hydrogenchloride; EXAMPLE 27 Cinnoline-4-carboxamide (27) A solution of 50.0 g of <strong>[52562-19-3]o-isopropenylaniline</strong> (Aldtich) in 440 ml of 2 N hydrochloric acid was treated with 86 ml of 12 N hydrochloric acid at 20 C. The resulting mixture was extracted with ether to remove a small amount of an insoluble oil. The aqueous phase was cooled to 0 C. and treared with 24.5 g of sodium nitrite, in portions, over 2 hours, at 0-5 C. The resulting mixture was stirred for 30 minutes at 0 C., warmed to room temperature, heated to 60 C., and then held at room temperature over a weekend. It was neutralized with sodium bicarbonate, made basic with 50% sodium hydroxide solution, and extracted with ether. The extract was washed with brine, dried (MgSO4), charcoaled, filtered and stripped of solvent. The residue was recrystallized from hexane to give 4-methylcinnoline (27A), as a solid, m.p.: 70-72 C.
  • 29
  • [ 19115-30-1 ]
  • [ 52562-19-3 ]
  • [ 141-97-9 ]
  • [ 1008132-57-7 ]
  • 30
  • [ 640291-86-7 ]
  • [ 52562-19-3 ]
  • [ 1161929-10-7 ]
  • 31
  • [ 52562-19-3 ]
  • [ 107574-36-7 ]
  • [ 1161929-11-8 ]
  • 32
  • [ 33626-98-1 ]
  • [ 52562-19-3 ]
  • C21H19NO2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
78% With tri-tert-butyl phosphine; palladium diacetate; caesium carbonate; In 5,5-dimethyl-1,3-cyclohexadiene; for 5h;Inert atmosphere; Reflux; (Synthesis of Exemplary Compound (A-7)) (0457) Compound (A-7) in which D1 in Formula (I) is a compound represented by Formula (III) may be prepared by the following reaction scheme. 2-iso-propynylaniline (4.20 g, 31.5 mmol), palladium acetate (210 mg, 0.95 mmol), tri(t-butyl)phosphine (570 mg, 2.80 mmol), cesium carbonate (20.5 g, 62.9 mmol) and methyl 6-bromo-2-naphthoate (8.35 g, 31.5 mmol) were dissolved in 50 ml of xylene, and reacted by boiling under reflux for 5 hours under a nitrogen atmosphere to obtain Compound 17 in 78% yield. Compound 17 (7.80 g, 24.6 mmol) was added to a mixed solvent of 40 ml of acetic acid and 8 ml of hydrochloric acid, and followed by stirring at 60 C. for 30 minutes to obtain Compound 18 in 82% yield. Compound 18 (1.00 g, 3.15 mmol), palladium acetate (70.7 mg, 0.315 mmol), tri(t-butyl)phosphine (191 mg, 0.945 mmol), cesium carbonate (2.05 g, 6.30 mmol) and 1-bromo-4-tert-butylbenzene (671 mg, 3.15 mmol) were dissolved in 15 ml of xylene, and reacted by boiling under reflux for 7 hours under a nitrogen atmosphere to obtain Compound 19 in 95% yield. A 70% solution of sodium bis(2-methoxyethoxy)aluminum dihydride in toluene (5.37 ml, 18.6 mmol) was added to 13 ml of THF under a nitrogen atmosphere, and cooled to 0 C. N-methylpiperazine (2.01 g, 20.1 mmol) was added dropwise, and stirred for 30 minutes to adjust a reducing agent solution. The reducing agent solution was added dropwise to 20 ml of a solution of Compound 19 (1.35 g, 3.00 mmol) in THF at -40 C. under a nitrogen atmosphere. The reaction solution was stirred at -20 C. for 4 hours, and the reaction was then stopped with diluted hydrochloric acid to obtain Compound 20 in 81% yield. Compound 20 (700 mg, 1.67 mmol) and benzindandione (361 mg, 1.84 mmol) were added to 9 ml of an acetic acid solvent under a nitrogen atmosphere, and refluxed for 3 hours. After allowing to cool, suction filtration was performed, and recrystallization was performed with N,N-dimethylacetamide. Suction filtration was performed to obtain Compound (A-7) in 51% yield. The compound was identified by 1H-NMR. (0460) 1H-NMR (400 M Hz, in CDCl3): δ (ppm)=1.45 (s, 9H), 2.31 (s, 6H), 6.09 (d, J=8.6 Hz, 1H), 6.53 (d, J=8.7 Hz, 1H), 6.89-6.98 (m, 2H), 7.22 (d, J=8.7 Hz, 2H), 7.48-7.56 (m, 2H), 7.63-7.72 (m, 4H), 8.04-8.12 (m, 3H), 8.47-8.57 (m, 3H), 8.69-8.73 (m, 1H), 8.79 (s, 1H). m.p.=335 C., λmax=568 nm (in CHCl3) (ε=53000 mol-1·l·cm-1)
With caesium carbonate;palladium diacetate; triphenylphosphine; In xylene; for 4h;Reflux; (Example 12) <Synthesis of Compound (12)> [Show Image]<Synthesis of Compound 12a"> To 50 ml of dehydrated xylene, 4.2 g of <strong>[52562-19-3]2-isopropenylaniline</strong> (produced by Aldrich Chemical Co. Inc.), 8.4 g of methyl 6-bromo-2-naphthoate (produced by Wako Pure Chemical Industries, Ltd.), 210 mg of palladium acetate, 740 mg of triphenylphosphine and 20.5 g of cesium carbonate were added, followed by refluxing for 4 hours. The reaction mixture was suction-filtered and after distilling off the solvent by an evaporator, the residue was purified on a silica gel column (developing solvent: toluene). The solvent was distilled off to obtain 7.8 g of Compound (12a").
  • 33
  • [ 52562-19-3 ]
  • [ 1361944-15-1 ]
  • 35
  • [ 52562-19-3 ]
  • [ 98-80-6 ]
  • [ 112817-88-6 ]
YieldReaction ConditionsOperation in experiment
53% General procedure: PhB(OH)2 (0.15 g, 1.2 mmol, 1.2 equiv), Cu(OAc)2 (0.036 g, 0.2 mmol, 0.2 equiv) and myristicacid (0.091 g, 0.4 mmol, 0.4 equiv) were dissolved in toluene (2 mL, 0.5M). The reaction wasstirred, 2,6-lutidine (0.12 mL, 1 mmol, 1 equiv) and <strong>[52562-19-3]2-isopropenylaniline</strong> (0.14 mL, 1 mmol, 1equiv) were added. The reaction was stirred at room temperature exposed to air for 24 h.TEMPO (0.031 g, 0.2 mmol, 0.2 equiv) and toluene (8 mL, 0.1M overall) were then added. Theflask was purged with O2, put under an O2 atmosphere using an O2 balloon and stirred for 24 h at120 oC. Filtration of the cooled reaction mixture through a pad of silica gel with ethyl acetate(100 mL), and subsequent evaporation of the solvent in vacuo afforded crude mixtures. Flashchromatography of the resulting crude mixture on silica gel (0-5% diethyl ether in hexanesgradient) afforded the known indole 2g (0.11 g, 53% yield) as a yellow liquid.
 

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