Structure of 401-93-4
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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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CAS No. : | 401-93-4 |
Formula : | C7H3ClF3NO2 |
M.W : | 225.55 |
SMILES Code : | FC(C1=CC([N+]([O-])=O)=CC(Cl)=C1)(F)F |
MDL No. : | MFCD03412202 |
InChI Key : | ZQXCQTAELHSNAT-UHFFFAOYSA-N |
Pubchem ID : | 50255 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H320-H335 |
Precautionary Statements: | P264-P270-P301+P312-P330 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 45.28 |
TPSA ? Topological Polar Surface Area: Calculated from |
45.82 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.54 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.26 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.42 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.53 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.39 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.63 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.48 |
Solubility | 0.0751 mg/ml ; 0.000333 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.9 |
Solubility | 0.0286 mg/ml ; 0.000127 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.29 |
Solubility | 0.116 mg/ml ; 0.000515 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) |
Yes |
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 |
-5.36 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 |
0.0 |
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) |
1.89 |
* 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 |
---|---|---|
100% | With tin(ll) chloride; In ethyl acetate; for 3.0h;Heating / reflux; | To a stirred mixture of l-chloro-3-nitro-5-(trifluoromethyl)benzene (2.90 g, 12.9 mmoL) in 120 mL of EtOAc, was added SnCl2 dihydrate (12.0 g, 51.6 mmoL). This mixture was heated to reflux for 3 h and cooled to room temperature. Next, the mixture was diluted with 100 mL of EtOAc and washed with 2.5N NaOH solution (Ix 150 mL). The aqueous layer was separated and extracted with EtOAc (Ix 200 mL). Combined EtOAc layers were washed with brine (Ix 40 mL), dried (MgSO4), filtered and concentrated in vacuo to give 2.51 g of Preparation 65A (3- chloro-5-(trifluoromethyl)aniline) as a yellow solid in quantitative yield.[00495] HPLC: 2.57 min (RT) (Chromolith SpeedROD column 4.6 x 50 mm, 10- 90% aqueous MeOH over 4 minutes containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm). MS (ES): m/z=196 [M+H]+. |
In methanol; aluminum nickel; | Step 2 92 g (0.408 mol) of <strong>[401-93-4]5-chloro-3-trifluoromethyl-nitrobenzene</strong> in 1 l of methanol are hydrogenated in the presence of 10.17 g of Raney nickel. The reaction mixture is filtered through Celite/activated carbon and the residue washed with methanol. Concentration of the filtrate by evaporation yields the oily 5-amino-3-chloro-benzotrifluoride; 1H-NMR (DMSO-d6) delta6.80 (m, 3H), 5.92 (s, H2N). | |
In methanol; aluminum nickel; | 111b 5-Amino-3-chloro-benzotrifluoride In the presence of 10.17 g of Raney nickel, 92 g (0.408 mol) of <strong>[401-93-4]5-chloro-3-trifluoromethyl-nitrobenzene</strong> are hydrogenated in 1 liter of methanol. The reaction mixture is filtered over Celite/activated carbon and the residue is washed with methanol. Concentration of the filtrate by evaporation yields the oily title compound: 1H-NMR (DMSO-d6) 6.80 (m, 3H), 5.92 (s, H2N); FAB-MS (M+H)+=196. |
b. 3-Chloro-5-trifluoromethylaniline Using a procedure similar to that described in Example 20a except starting with <strong>[401-93-4]3-chloro-5-trifluoromethylnitrobenzene</strong>, the title compound was obtained (77%) as an amber oil; MS(CI): 196 (M+H). 250-MHz 1 H NMR (DMSO-d6): 6.82 (s, 1H), 6.79 (s, 1H), 6.77 (s, 1H), 5.94 (s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; sulfuric acid; sodium nitrite; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; ethanol; | Step 1 56.7 ml of 96% sulphuric acid are added dropwise over 30 min to a brown solution of 90 g (374 mmol) of 4-amino-3-chloro-5-nitro-benzotrifluoride (Maybridge; Tintagel/England) in 500 ml of ethanol (exothermic). After heating to 75 C., 64.53 g (935 mmol) of sodium nitrite are added in portions over 1 h (gas evolution). Stirring is effected for 2.5 h at 75 C., followed by cooling to RT. The reaction mixture is poured onto 1.5 l of ice water and extracted 4 times with diethylether. Washing of the organic phase with 0.1 N HCl, sat. NaHCO3 solution and brine, drying (Na2SO4) and concentrating by evaporation yield a brown oil. Column chromatography (SiO2; hexane) yields 5-chloro-3-trifluoromethyl-nitrobenzene as an oil; 1H-NMR (DMSO-d6) delta8.62 (m, 1 H), 8.46 (m, 2H). | |
With hydrogenchloride; sulfuric acid; sodium nitrite; In ice-water; ethanol; | 111a 5-Chloro-3-trifluoromethyl-nitrobenzene (see also: EP 0 516 297 A1) 56.7 ml of 96% sulfuric acid are added dropwise over a period of 30 minutes to a brown solution of 90 g (374 mmol) of 4-amino-3-chloro-5-nitro-benzotrifluoride (Maybridge; Tintagel/England) in 500 ml of ethanol (exothermic). After heating to 75 C., 64.53 g (935 mmol) of sodium nitrite are added in portions over a period of one hour (evolution of gas). The mixture is stirred for 2.5 hours at 75 C. and then cooled to room temperature. The reaction mixture is poured onto 1.5 liters of ice-water and extracted four times with ether. Washing the organic phases with 0.1 N HCl, saturated NaHCO3solution and brine, drying (Na2SO4) and concentration by evaporation yield a brown oil. Column chromatography (SiO2; hexane) yields the title compound in the form of an oil: 1H-NMR (DMSO-d6) 8.62 (m, 1H), 8.46 (m, 2H), MS 225 (M)+, 179 (M-NO2)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
a. 3-Chloro-5-trifluoromethylnitrobenzene To a stirred solution of 2-chloro-6-nitro-4-trifluoroaniline (20.0 g, 83.1 mM) in ethanol (110 mL) was added dropwise concentrated sulfuric acid (12.6 mL). The resulting stirred solution was heated to reflux and sodium nitrite (14.34 g, 207.9 mM) was added in portions, whereupon a precipitate formed. After the addition was completed, the reaction mixture was refluxed for 3 hr, cooled and poured into water. The resulting mixture was extracted with ether and the combined extracts were dried (MgSO4), filtered and concentrated. The residue was chromatographed (eluant: hexane/diethyl ether; 98/2?80/20) over silica gel to provide (10.9 g, 58%) the title compound as a yellow oil: MS(CI): 226 (M+H). 300-MHz 1 H NMR (DMSO-d6): 8.62 (s, J=2.0 Hz,iH), 8.47 (m, 2H). |
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