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Structure of 3300-51-4

Chemical Structure| 3300-51-4

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Product Citations

Product Citations

Robert Kawȩcki ;

Abstract: N-Sulfenylimines (sulfenimines, thiooximes, N-alkylidenesulfenamides) were efficiently synthesized through the reaction of primary amines and disulfides with NBS or bromine. This reaction can be carried out in an open flask at room temperature without the need for any transition-metal-containing additives. The use of thiols instead of disulfides gave similar results. A wide range of amines were reacted with aryl and alkyldisulfides, resulting in the formation of sulfenimines in a yield of 44–99%.

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Product Details of [ 3300-51-4 ]

CAS No. :3300-51-4
Formula : C8H8F3N
M.W : 175.15
SMILES Code : C1=C(C=CC(=C1)CN)C(F)(F)F
MDL No. :MFCD00010220
InChI Key :PRDBLLIPPDOICK-UHFFFAOYSA-N
Pubchem ID :76804

Safety of [ 3300-51-4 ]

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

Computational Chemistry of [ 3300-51-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 39.12
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.

1.7
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

1.98
Log Po/w (WLOGP)?

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

3.16
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.

2.61
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

2.44
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.38

Water Solubility

Log S (ESOL):?

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

-2.41
Solubility 0.679 mg/ml ; 0.00388 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.

-2.15
Solubility 1.23 mg/ml ; 0.00704 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

-3.33
Solubility 0.0827 mg/ml ; 0.000472 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

No
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.

-5.96 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

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)

1.0

Application In Synthesis of [ 3300-51-4 ]

* 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 [ 3300-51-4 ]

[ 3300-51-4 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 40359-32-8 ]
  • [ 3300-51-4 ]
  • [ 864148-10-7 ]
  • 2
  • [ 16176-74-2 ]
  • [ 3300-51-4 ]
  • 2-(1<i>H</i>-indol-4-yl)-<i>N</i>-(4-trifluoromethyl-benzyl)-acetamide [ No CAS ]
  • 3
  • [ 389602-62-4 ]
  • [ 3300-51-4 ]
  • [ 68957-94-8 ]
  • [ 389601-55-2 ]
YieldReaction ConditionsOperation in experiment
48% With 4-methyl-morpholine; In dichloromethane; EXAMPLE 49 N-(4-trifluoromethyl-phenylmethyl)-3-(4'-trifluoromethyl-biphenyl-2-carbonylamino)-benzoic acid amide Prepared analogously to Example 7 from 3-(4'-trifluoromethylbiphenyl-2-carbonylamino)-benzoic acid and 4-trifluoromethyl-benzylamine in dichloromethane with the addition of propanephosphonic acid cycloanhydride and N-methylmorpholine. Yield:48% of theory Rf value:0.63 (silica gel; dichloromethane/ethanol=9:1)
  • 4
  • [ 3300-51-4 ]
  • [ 95652-77-0 ]
  • [ 1073230-29-1 ]
YieldReaction ConditionsOperation in experiment
In 1,2-dimethoxyethane; for 48h;Heating / reflux; A mixture of 1.0 g (5.0 mmol) of the compound of Step B and 4-(trifluoromethyl)- benzylamine (1.82 g, 10.4 mmol) in DME (25 mL) was refluxed for 48 h. The resulting mixture was filtered and washed with DME. The combined filtrate was evaporated followed by the purification silica column (combiflash, ISCO) and eluted with hexane + EtOAc (0 to 10% gradient) to give 1.49 g of the title compound as an off white solid: 1H NMR (500 MHz, CDCl3) delta 8.63 (br s, IH), 8.04 (d, IH, J = 8.5 Hz), 7.59 (d, 2H, J = 7.3 Hz), 7.48 (d, 2H, J = 7.2 Hz), 6.02 (d, IH, J = 8.5 Hz), 4.81 (d, 2H, J = 5.5 Hz), 3.86 (s, 3H), 3.81 (s, 3H); MS: m/z 341 (M+H).
  • 5
  • [ 5900-59-4 ]
  • [ 3300-51-4 ]
  • [ 1221128-83-1 ]
YieldReaction ConditionsOperation in experiment
40% With dihydrogen peroxide; In water; at 120℃; for 20h;Sealed tube; General procedure: A 15 mL tube was added 2-aminobenzamide (1mmol), benzyl amine (1.5mmol), and a stir bar. Then H2O2 (30 wtpercent in H2O, 5 equiv.) was added by a syringe at room temperature under open air. The tube was closed and kept at 120°C for 20 h. The conversion and yield were determined by GC and GC?MS using hexadecane (0.1 mmol) as the internal standard.
  • 6
  • [ 57595-23-0 ]
  • [ 3300-51-4 ]
  • methyl 4-((4-(trifluoromethyl)benzyl)amino)-2,5-dihydrofuran-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With acetic acid; In ethanol; at 90℃; for 5h; To a solution of methyl 4-oxotetrahydrofuran-3 -carboxylate (11, 50 g, 350 mmol) in anhydrous EtOH (1000 mL) was added (4-(trifluoromethyl) phenyl)methanamine (64 g, 360 mmol), followed by AcQH (60 mL). The reaction mixture was then heated to 90C and stirred for 5 hours when TLC showed that the reaction completed. The reaction mixture was concentrated under reduced pressure to removemost of the solvent. The residue was partitioned between EtOAc (1000 mL) and H20 (1000 mL), and the organic phase was washed with H20 (1000 mL) and brine (1000 mL), dried over Na2SO4 and concentrated under reduced pressure to afford methyl 4-((4-(trifluoromethyl)benzyl)amino)-2,5- dihydrofuran-3-carboxylate (12) as a solid, which was used directly in next step without further purification. LC/MS (m/z): 302 (M+H).
  • 7
  • [ 3300-51-4 ]
  • [ 1180-71-8 ]
  • 2-((1S,3aS,4aR,4bR,9aR,11aS)-1-(furan-3-yl)-9a-(hydroxymethyl)-4b, 7,7,11a-tetramethyl-3,5-dioxotetradecahydroisobenzofuro[5,4-f]oxireno[2,3-d]isochromen-9-yl)-N-(4-(trifluoromethyl)benzyl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With montmorillonite K-10; In ethanol; at 80℃; for 0.5h;Sealed tube; Microwave irradiation; General procedure: To a solution of 1 (2.0 mmol) in absolute EtOH (8.0 mL)in a glass tube was added dropwise the appropriate amine(3.6 mmol) and K-10 (0.3 g mmol-1); the quartz tubewas sealed with reaction mixture and introduced intoa microwave oven. The flask was irradiated for 30 min(150 W) the temperature of 80 C. After completion of thereaction the mixture was filtered, the organic phase wasdried with Na2SO4, filtered and the solvent was evaporatedunder reduced pressure to give the crude products. All thecompounds were purified by column chromatographyon silica gel using 2-5% EtOH-CH2Cl2 as eluent to giveanalytically pure products 3a-m. The products werecharacterized by corresponding spectroscopic data (1H and13C NMR, and HRMS).
  • 8
  • [ 21279-62-9 ]
  • [ 3300-51-4 ]
  • 3-[(4-trifluoromethylbenzyl)amino]pyrazine-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
46% With pyridine; In methanol; at 140℃; for 0.5h;Sealed tube; Microwave irradiation; General procedure: Compounds 1-6 were prepared according to conventional organic synthesis methods. 3-Chloropyrazine-2-carboxamide (1.27 mmol) was dissolved in THF (20 mL) in a round bottom flask and after that treated with two equivalents of the corresponding benzylamine and an equimolar amount of triethylamine. The reaction was conducted with continuous stirring and heating (70 C) under reflux in an oil bath for 15 h. Compounds 7-15 were synthesised using a microwave reactor with a focused field. 3-Chloropyrazine-2-carboxamide (1.27 mmol) was put into a thick-walled tube together with the corresponding benzylamine (2.54 mmol), pyridine (1.27 mmol), methanol (approx. 5 mL) and a magnetic stir bar and then sealed with a special cap. The reaction parameters were set according to the previously published paper as follows-140 C, 30 min, 200 W [29]. Reaction progress was checked by TLC (hexane:ethyl acetate-1:1). Regardless of the synthesis method used,all reaction mixtures were adsorbed on silica and subjected to preparative flash chromatography (hexane and ethyl acetate, gradient elution, detection wavelengths 260 nm and 280 nm). Products were recrystallized from ethanol or ethanol and water if necessary. All final substances were chemically characterized (1H-NMR, 13C-NMR, IR, melting point and elemental analysis).
 

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