Structure of 367-34-0
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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. : | 367-34-0 |
Formula : | C6H4F3N |
M.W : | 147.10 |
SMILES Code : | C1=C(F)C(=CC(=C1N)F)F |
MDL No. : | MFCD00007649 |
InChI Key : | QMYVWJVVVMIBMM-UHFFFAOYSA-N |
Pubchem ID : | 94953 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 30.72 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.02 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.47 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.54 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.95 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.78 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.4 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.23 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.17 |
Solubility | 1.0 mg/ml ; 0.00682 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.7 |
Solubility | 2.96 mg/ml ; 0.0202 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.85 |
Solubility | 0.205 mg/ml ; 0.0014 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 |
-6.1 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 |
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) |
1.24 |
* 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 |
---|---|---|
92% | With pyridine; for 2h;Heating; | A solution of 2,4,5 -trifluoroaniline 11 (25 g, 170 mmol) in anhydrous pyridine (14.4 mL, 178 mmol) was treated with acetic anhydride (16.9 mL, 178 mmol) and heated to 120 °C for 2 hours. After cooling to room temperature, the solution was poured into ice-cold water (150 mL). The resulting precipitate was filtered, dissolved in ethyl acetate, dried over anhydrous Na2S04, filtered, and concentrated. The residue was dried to give 2,4,5- trifluoroacetanilide (12) (29.63 g, 92percent) as a yellow solid. 1H NMR (CDC13, 400MHz) delta 8.35- 8.26 (m, 1 H), 7.01-6.93 (m, 1 H), 2.22 (s, 3 H); 19F NMR (CDC13) delta -133.45 - -133.54 (m, IF), -139.56 - -139.67 (m, IF), -140.14 - -140.28 (m, IF). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 40 By the procedure similar to that employed in Example 33, ethyl 2-chlorosulfonyl-1-cyclohexene-1-carboxylate (0.40 g) obtained in Reference Example 2 was reacted with <strong>[367-34-0]2,4,5-trifluoroaniline</strong> (0.31 g) to yield ethyl 6-[N-(2,4,5-trifluorophenyl)sulfamoyl]-1-cyclohexene-1-carboxylate (Compound 43; 0.30 g) as white crystals. 1H-NMR (d6-DMSO)delta: 1.13 (3H, t, J=7.0 Hz), 1.55-1.85 (2H, m), 1.96-2.48 (4H, m), 4.05 (2H, q, J=7.0 Hz), 4.35 (1H, d, J=4.4 Hz), 7.14 (1H, br), 7.47-7.71 (2H, m), 10.17 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In water; acetic acid; at 20℃; for 18h; | Intermediate 3: (2,4,5-TrifluorophenvDurea; <strong>[367-34-0]2,4,5-Trifluoroaniline</strong> (736 mg; 5.00 mmol) was dissolved in glacial acetic acid (2.4 mL) and water (4.8 mL). To this solution was added slowly, with stirring at ambient <n="51"/>temperature, a solution of sodium cyanate (651 nig; 10.00 mmol). Almost at once, a white precipitate formed. The mixture was stirred for 18hrs at RT. The mixture was cooled to 0 °C, before filtration. The crude solid product was washed with a little water and dried, then dissolved in 5 mL of a mixture of DMSO:CH3CN: Water (70:20:10) and chromatographed on a Merck HyperPrep BDS Cl 8 15 mum column, usingH2O:CH3CN(20percent-90percent):TFA(0.2percent). Product fractions were collected and evaporated to colourless needles which were dried to give the title product (521mg). 1H NMR delta 6.10 (s, 2H), 7.53 (q, IH), 8.08 - 8.27 (m, IH)5 8.41 (s, IH). MS m/e MH+ = 191.10 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With nitrosylsulfuric acid; In water; acetic acid; at -20 - 30℃; for 1h; | PREPARATION EXAMPLES EXAMPLE 1 4.4 g (30 mmol) of <strong>[367-34-0]2,4,5-trifluoro-aniline</strong> are dissolved in 25 ml of acetic acid ("glacial acetic acid") and cooled using an ice-bath.. With stirring, 4.5 g (31.5 mmol) of nitrosylsulphuric acid are then added, the ice-bath is removed and the reaction mixture is stirred for an additional hour (first step). With stirring, the resulting diazonium salt solution is then added to a solution, cooled to 5° C., of 7.8 g (160 mmol) of sodium cyanide and 0.3 g (3 mmol) of copper(I) cyanide in 40 ml of water.. By simultaneous addition of approximately 80 ml of a 25percent strength aqueous solution of sodium carbonate, the PH is maintained approximately in the neutral range.. The reaction mixture is subsequently stirred for approximately another 15 minutes and then extracted twice with 100 ml of ethyl acetate each time.. The solvent is carefully distilled off under water pump vacuum from the combined organic extraction solutions. This gives 4.1 g (92percent pure product according to gas chromatographic analysis, i.e. 80percent of theory) of 2,4,5-trifluoro-benzonitrile as an oily residue. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
8.2% | To a solution of 2 g (13. [6 MMOL) OF] 2,4, 5-trifluorophenylamine and 2.66 g (13.9 [MMOL)] of 5-bromothiophene-2-carbaldehyde in 30 ml of EtOH, 9.4 g of molecular sieves (0.3 nm) were added and the mixture was refluxed for 20 hours. After this time the reaction mixture was cooled to room temperature, filtered and the solvent was evaporated in vacuo. The oil obtained was dissolved in 30 ml of [MEOH] and 0.51 g (13.6 [MMOL)] of NaBH4 were added in small portions, maintaining the temperature of the reaction at room temperature. The mixture was stirred at this temperature for 20 more hours. After this time the solvent was evaporated in vacuo and the residue was treated with 100 [ML] of water and extracted twice with ether. The organic layers were combined, washed with brine, dried over anhydrous MgSO4, filtered and evaporated to dryness to give 3.2 g of an oil. This 3. [2 G] were combined with 3. [5 G] obtained in a subsequent preparation and the total product obtained (6.7 g) was purified by chromatography on silica gel using mixtures of hexane/AcOEt 5: [1# ] 1: 1 as eluent. Appropriate fractions were combined to give 0.95 g of the title product as an oil. (global yield 8. [2percent).] MS [[M+1] + :] 321,323 [1H-NMR (CDC13) : 64.] 10 (bs, NH, [1H),] 4.40 (s, 2H), 6.40-6. 65 (m, 1H), 6.75-7. 10 (m, 3H). |
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