Structure of 168966-54-9
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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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CAS No. : | 168966-54-9 |
Formula : | C6H5F3N2 |
M.W : | 162.11 |
SMILES Code : | NC1=CC(F)=C(F)C(F)=C1N |
MDL No. : | MFCD01569524 |
InChI Key : | WWDBSPRMQHYOOQ-UHFFFAOYSA-N |
Pubchem ID : | 2773958 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 35.12 |
TPSA ? Topological Polar Surface Area: Calculated from |
52.04 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.11 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.86 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.54 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.12 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.7 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.67 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.79 |
Solubility | 2.63 mg/ml ; 0.0162 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.54 |
Solubility | 4.71 mg/ml ; 0.0291 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.51 |
Solubility | 0.504 mg/ml ; 0.00311 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 |
-6.68 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 |
1.0 |
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 |
2.0 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) |
1.31 |
* 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 |
---|---|---|
70% | With hydrogenchloride; tin; for 1.5h;Reflux; | Concentrated HCl (15 mL) was slowly added dropwise to a mixture of nitroaniline 8, 13c-d (12 mmol), and tin (30 mmol). The reactionmixture was heated at reflux for 1.5 h, cooled to r.t., and neutralizedwith 50% NaOH solution to pH 9-10. The precipitate was filtered off,dried, and extracted with hot EtOAc (80 mL). Diamines 10 and 14c-dwere obtained after evaporation of filtrates.3,4,5-Trifluoro-1,2-phenylenediamine (10)Yield: 1.40 g (70%); brown crystals; mp 85-87 C; Rf 0.72 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | aluminum nickel; In ethanol; water; hydrogen; | A. 3,4,5-Trifluoro-1,2-phenylenediamine 1,2,3-Trifluoro-6-nitroaniline (15.0 g, 78.1 mmol, Aldrich, Milwaukee), Raney nickel (Aldrich, Milwaukee, slurry in water, 1.0 g wet) and ethanol (100 mL) were placed in a Parr reactor which was pressurized with hydrogen (175 psig) and stirred. The resulting mixture was allowed to stir overnight at rt, after which time it was filtered through Celite and the solvents were removed in vacuo to provide a dark oil. The title compound was purified by silica gel chromatography using 3:2 hexane-ethyl acetate as eluent to provide a brown solid (9.6 g, 76%); 1H NMR (DMSO-d6) delta: 6.30 (m, 1 H, Ar-H), 4,91 (br s, 2H, NH2), 4.52 (br s, 2H, NH2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
285 mg (25%) | With KNO3; sulfuric acid; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; ethyl acetate; | 3,4,5-Trifluoro-1,2-phenylenediamine. To 2,3,4-trifluoroacetanilide (1.35 g, 7.09 mmol) is added concentrated sulfuric acid (8 mL). While the flask is in an ice bath, KNO3 is slowly added, giving a tan mixture, that is stirred overnight. The reaction mixture, now dark red, is then added to ice water (45 mL), instantly giving an orange precipitate. The volatile compound, presumably 2,3,4-trifluoro-6-nitroaniline, is dissolved in ethyl acetate (18 mL) and ethyl alcohol (12 mL). To the orange solution is added stannous chloride dihydrate (7.6 g, 34 mmol). The resulting mixture is stirred and brought to reflux under N2 for 4 h. The mixture is added to ice water (40 mL) and basified with 2N NaOH (40 mL). It is extracted with ethyl acetate (3*20 mL) and the combined extracts are washed with water (20 mL) and brine (20 mL). This dark red solution is dried (MgSO4) and evaporated to give 285 mg (25%) of the diamine as a dark red solid. 1 H NMR (CDCl3), 3.22 (br s, 2H), 3.46 (br s, 2H), 6.32 (m, 1H). |
285 mg (25%) | With KNO3; sulfuric acid; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; ethyl acetate; | 3,4,5-Trifluoro-1,2-phenylenediamine To 2,3,4-trifluoroacetanilide (1.35 g, 7.09 mmol) is added concentrated sulfuric acid (8 mL). While the flask is in an ice bath, KNO3 was slowly added, giving a tan mixture, which was stirred overnight. The reaction mixture, now dark red, was then added into ice water (45 mL), instantly giving an orange precipitate. The volatile compound, presumably 2,3,4-trifluoro-6-nitroaniline, is dissolved in ethyl acetate (18 mL) and ethyl alcohol (12 mL). To the orange solution is added stannous chloride dihydrate (7.6 g, 34 mmol). The resulting mixture is stirred and brought to reflux under N2 for 4 h. The mixture is added into ice water (40 mL) and basified with 2N NaOH (40 mL). It was extracted with ethyl acetate (3*20 mL) and the combined extracts were washed with water (20 mL) and brine (20 mL). This dark red solution is dried (MgSO4) and evaporated to give 285 mg (25%) of the diamine as a dark red solid. 1 H NMR (CDCl3), 3.22 (br s, 2H), 3.46 (br s, 2H), 6.32 (m, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
15 mg (36%) | With oxalic acid; In hydrogenchloride; ethanol; | 5,6,7-Trifluoro-1,4-dihydro-2,3-quinoxalinedione. To a brown solution of <strong>[168966-54-9]3,4,5-trifluoro-1,2-phenylenediamine</strong> (285 mg, 1.75 mmol) in aqueous 2N HCl (10 mL) is added oxalic acid (221 mg, 1.75 mmol). The brown mixture is brought to reflux and stirred under N2 overnight. The mixture is filtered to yield 139 mg (37%) of crude title compound. An analytical sample is prepared by dissolving 42 mg of this brown powder in 2.5 mL boiling ethanol. Upon cooling, brown, rod-like, crystals are formed, which are filtered and dried in vacuo to yield 15 mg (36%) of pure title compound: 1 H NMR (DMSO-d6), 6.91 (m, 1H), 12.02 (s, 1H), 12.19 (s, 1H); analysis calculated for C8 H3 F3 N2 O2: C, 44.46; H, 1.40; N, 12.96. Found: C, 44.42; H, 1.16; N, 12.76. |
15 mg (36%) | With oxalic acid; In hydrogenchloride; ethanol; | 5,6,7-Trifluoro-1,4-dihydro-2,3-quinoxalinedione To a brown solution of <strong>[168966-54-9]3,4,5-trifluoro-1,2-phenylenediamine</strong> (285 mg, 1.75 mmol) in aqueous 2N HCl (10 mL) is added oxalic acid (221 mg, 1.75 mmol). The brown mixture is brought to reflux and stirred under N2 overnight. The mixture is filtered to yield 139 mg (37%) of crude title compound. An analytical sample is prepared by dissolving 42 mg of this brown powder in 2.5 mL boiling ethanol. Upon cooling, brown rod-like crystals were formed which are filtered and dried in vacuo to yield 15 mg (36%) of pure title compound: 1 H NMR (DMSO-d6), 6.91 (m, 1H), 12.02 (s, 1H), 12.19 (s, 1H); analysis calculated for C8 H3 F3 N2 O2: C, 44.46; H, 1.40; N, 12.96. Found: C, 44.42; H, 1.16; N, 12.76. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | for 4.0h;Reflux; | General procedure: Compounds 10 and 14a-d (6 mmol) were heated at reflux in formicacid (30 mL) for 4 h. The reaction mixture was then evaporated undervacuum, poured into H2O (50 mL) and neutralized with a 10% solutionof NaOH (20 mL) to pH 7. The precipitate was filtered off, dried, andrecrystallized from a mixture H2O-MeCN (1:1). |
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