Structure of 3300-51-4
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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Synthesis of N-Sulfenylimines from Disulfides and Primary Methanamines
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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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 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
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 |
26.02 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.7 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.98 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.16 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.61 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.44 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.38 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.41 |
Solubility | 0.679 mg/ml ; 0.00388 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.15 |
Solubility | 1.23 mg/ml ; 0.00704 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.33 |
Solubility | 0.0827 mg/ml ; 0.000472 mol/l |
Class? Solubility class: Log S scale |
Soluble |
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) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.96 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
2.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.0 |
* 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.
Yield | Reaction Conditions | Operation 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) |
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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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