Structure of 445-13-6
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CAS No. : | 445-13-6 |
Formula : | C7H5ClF3N |
M.W : | 195.57 |
SMILES Code : | NC1=CC=C(C(F)(F)F)C(Cl)=C1 |
MDL No. : | MFCD00278479 |
InChI Key : | KZAMRRANXJVDCD-UHFFFAOYSA-N |
Pubchem ID : | 67962 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H317-H319 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 40.86 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.02 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.65 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.75 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.1 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.15 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.77 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.88 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.09 |
Solubility | 0.159 mg/ml ; 0.000815 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.95 |
Solubility | 0.219 mg/ml ; 0.00112 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.54 |
Solubility | 0.0558 mg/ml ; 0.000285 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 |
-5.54 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 |
1.0 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 |
---|---|---|
With sodium tetrahydroborate; In water; at 55℃; for 3h;Green chemistry; | General procedure: To the corresponding nitro aromatic compound (1 mmol) in3mL water, 40 mg catalyst was added and the suspension wasstirred vigorously at ambient temperature. Subsequently, 2 mmolNaBH4 was added and the mixture heated to 55 C. Afterwards, theprogress of reduction process was monitored using thin layerchromatography until the complete reduction of nitro groups. After the reduction reaction completed, the catalyst was removed withan external magnet and washed with ethanol. The products werepurified by a short column chromatography over silica gel to obtainthe corresponding compounds in high purity. 1H NMR spectra andcomparison of melting points to authentic samples were used forrecognizing of the reaction products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Example 45 N4-(3-Chloro-4-trifluoromethyl-phenyl)-N2,N2-dimethyl-7-(3-trifluoro-methyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine The title compound was synthesized like Example 39 with modifications to Step C as follows: Step C. A mixture of [4-chloro-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido-[4,5-d]azepin-2-yl]-dimethyl-amine (50 mg, 0.14 mmol), 3-chloro-4-trifluoro-methylaniline (40 mg, 0.20 mmol), and p-toluenesulfonic acid (51 mg, 0.27 mmol) in toluene (2 mL) was heated in a sealed tube at 120 C. for 18 h. The mixture was cooled, diluted with satd. aq. NaHCO3, and extracted with CH2Cl2. The organic layer was dried (MgSO4) and concentrated. The residue was purified (FCC) to give the title compound (55 mg, 78%). MS (ESI): mass calcd. for C23H21ClF6N6, 530.14; m/z found, 531.8 [M+H]+. 1H NMR (CD3OD): 8.43-8.40 (m, 1H), 8.25 (d, J=1.9 Hz, 1H), 8.08-7.98 (m, 1H), 7.66-7.62 (m, 1H), 7.57 (d, J=8.8 Hz, 1H), 7.11-7.08 (m, 1H), 3.45-3.39 (m, 4H), 3.33-3.31 (m, 1H), 3.13 (s, 6H), 3.06-3.03 (m, 2H), 2.97-2.93 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Following the procedure of N. Ikemoto et al. (Tetrahedron, 59:1317 (1998)), <strong>[445-13-6]3-chloro-4-trifluoromethylaniline</strong> (890 mg, 4.6 mmol, Ryan Scientific) in CH3CN (37 mL) was added to a 250 mL round-bottomed flask. The flask was cooled in an ice bath, and HOAc (3.7 mL) and HCl (12 M, 1.8 mL) were added. Sodium nitrite (380 mg, 5.5 mmol, Aldrich) in 0.77 mL of H2O was added in 0.15 mL portions every 2 min until all of the solution had been added (total time ca. 9 min). After 25 min, sulfur dioxide (Aldrich) was bubbled into the reaction mixture for 1.25 h. Copper(II)chloride (780 mg, 5.8 mmol, Aldrich) in 1.5 mL of water was then added to the reaction mixture. Gas evolution occurred, and the reaction was warmed to RT and stirred overnight. After the lower boiling solvents were removed in vacuo, water was added, and the mixture was extracted with CH2Cl2 (3×). The combined organic layers were washed with water, dried over MgSO4, filtered and concentrated in vacuo to give the crude material as a brownish oil with solid in it. The compound did not ionize well, but an aliquot, when treated with propylamine, provided the propylarylsulfonamide adduct with a ESI-MS, -ion, m/z=300.2 (M-1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With sulfuric acid; water; sodium nitrite; at 0 - 110℃; for 3h;Heating / reflux; | To a sulfuric acid (14 ml) -H2O (14 ml) solution of <strong>[445-13-6]3-chloro-4-(trifluoromethyl)aniline</strong> (1.96 g, 10 mmol) was added a H2O (10 mL) solution of sodium nitrite (828 mg,12 mmol) at 0 C. The reaction mixture was stirred at ambient temperature for 1 hour. The mixture was poured into 10 M sulfuric acid (50 mL). The stirred mixture was refluxed at 110 C. for 2 hours. The reaction mixture was then quenched with saturated aqueous solution of sodium bicarbonate and then crude products were extracted with ethyl acetate The organic layer was then washed with brine, dried over sodium sulfate. After the filtration to separate solvent and sodium sulfate, the solvent was removed under reduced pressure to give the residue, which was applied to a silica gel chromatography column and eluted with a ethyl acetate/hexane= to furnish 945 mg (48% yield) of the title compound as a brown oil. 1H NMR (CDCl3, 270 MHz) delta ppm 5.99 (1H, brs), 6.80 (1H, dd, J=2.6, 8.6 Hz), 7.00 (1H, d, J=2.6 Hz), 7.56 (1H, d, J=8.6 Hz). MS (ESI) m/z: 195[M-H-. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; In tetrahydrofuran; for 18h; | Phenyl [3-chloro-4-(trifluoromethyl)phenyl]carbamate; Phenyl chloroformate (0.86 mL) was added slowly to a stirring solution of 3-chloro-4- trifluoromethyl aniline (933 mg) in THF (10 mL) containing pyridine (1.07 mL) under an argon atomosphere. The reaction was stirred for 18 h then diluted with ethyl acetate (35 mL) and IM HCl (20 mL). The organic layer was separated and washed with saturated aqueous NaHCO3 then dried (MgSO4), filtered and evaporated. Trituration with 1:9 EPO <DP n="183"/>EtOAc dsohexanes (10 mL) at reflux followed by cooling to RT afforded a solid which was filtered to afford 1.15 g of the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With pyridine; In dichloromethane; for 2h; | l^^-Trichloro-N-tS-chloro^^trifluoromethy^phenyllacetaiiiide; To a solution of 4-amino-2-chlorobenzotrifluoride (300 mg) and pyridine (243 mg) in dichloromethane (1OmL) was added a solution of trichloro acetyl chloride (279 mg) in dichloromethane (5mL) dropwise. The solution was stirred for 2hrs and then concentrated at reduced pressure. The residue was purified by silica gel chromatography eluting with 0-10% ethyl acetate in hexane to give the title compound as a white solid (360mg, 69%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
iV-tS-CIiloro^-CtrifluoromethylJphenyy^-fCl-methylpiperidin-S- yl)methyl]pipera-ne-l-carboxaniotaide; To a solution of di-tert-butyl dicarbonate (114.6 mg) in chloroform (2 ml) was added 4-dimethylaminopyridine (6 mg). A solution of 4-amino-2-chlorobenzotrifluoride(98.1 mg) in chloroform (2 ml) was added and the reaction mixture stirred for 20 minutes at room temperature. A solution of l-[(l-methylpiperidm-3-yl)methyl]piperazine (98.5 mg) in chloroform (2 ml) was added and the resulting solution was stirred at reflux for 18 hours. The reaction mixture was purified by column chromatography on silica gel (20 g) using a gradient of 100% dichloromethane through to 20% methanolic ammonia in dichloromethane to give the title compound (14 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With triethylamine; In 1,2-dichloro-benzene; | Example 2 (variant b) STR11 0.5 mol of chloroformic acid phenyl ester is added to a solution of 0.5 mol of p-fluoroaniline in 300 ml of dichlorobenzene and 70 ml (0.5 mol) of triethylamine, whilst cooling (0-10 C.). The reaction mixture is then left to stand at room temperature for 24 hours. The triethylamine hydrochloride which has formed is filtered off and 0.5 mol of <strong>[445-13-6]3-chloro-4-trifluoromethylaniline</strong> is added to the filtrate. The reaction solution is heated to 180 C. for 6 hours, the solvent is stripped off in vacuo and the residue is boiled up in 250 ml of ether and filtered off again. N-4-Fluorophenyl-N'-3-chloro-4-trifluoromethylphenylurea of melting point 212 to 214 C. is obtained. Yield: 67% of theory. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
It was prepared by diazotizing of 3-chloro-4-trifluoromethylaniline and subsequent reduction of the corresponding phenyldiazonium chloride with tin(II) chloride. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With Iodine monochloride; In methanol; dichloromethane; at 0℃; | Step 1 5-Chloro-2-iodo-4-(trifluoromethyl)phenylamine A 250 mL 3-necked round bottom flask was charged with <strong>[445-13-6]3-chloro-4-(trifluoromethyl)aniline</strong> (4.5 g, 0.02 mol) and MeOH (50 mL). To the above was added dropwise a solution of IC1 (4.8 g, 0.03 mol) in CH2Cl2 (100 mL) at 0 C. The resulting mixture was stirred at room temperature for 1 h. Reaction progress was monitored by TLC (EtOAc/Petroleum ether=1:20, Rf=0.6). Work-up: the mixture was concentrated in vacuo. The residue was re-dissolved in CH2Cl2, washed with water, dried over anhydrous Na2SO4 and concentrated in vacuo, to give 6.9 g (93%) of the product. MS m/z: 320 (M-H+). |
93% | With Iodine monochloride; In methanol; dichloromethane; at 0 - 20℃; for 1h; | A 250 mL 3-necked round bottom flask was charged with 3-chloro-4- (trifluoromethyl)aniline (4.5 g, 0.02 mol) and MeOH (50 mL). To the above was added dropwise a solution of ICl (4.8 g, 0.03 mol) in CH2C12 (100 mL) at 0 C. The resulting mixture was stirred at room temperature for 1 h. Reaction progress was monitored by TLC (EtO Ac/Petroleum ether = 1 :20, Rf = 0.6). Work-up: the mixture was concentrated in vacuo. The residue was re-dissolved in CH2C12, washed with water, dried over anhydrous Na2SC>4 and concentrated in vacuo, to give 6.9 g (93%) of the product. MS m/z: 320 (M-H+). |
With sodium acetate; Iodine monochloride; In acetic acid; at 20℃; for 0.5h; | Iodine monochloride (1.5 g) was added in one portion to a mixture of 3-chloro-4- trifluoromethylaniline (1.7 g), sodium acetate trihydrate (2.2 g), and acetic acid (10 ml) at room temperature. After 30 min aqueous sodium bicarbonate / sodium sulfite was added and the mixture extracted with diethyl ether. The organic phase was dried over Na2SO4, filtered and evaporated. The residue was purified by chromatography (ethyl acetate - hexane) to afford the title compound, 2.2 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With tert.-butylnitrite; copper(ll) bromide; In acetonitrile; at 45℃; for 3h; | A solution of 4-amino-2-chlorobenzotrifluoride (9.780 g; 50.007 mmol) in MeCN (65 ml) was treated with copper(ll) bromide (1 1.169 g; 50.007 mmol), and the green heterogeneous mixture was heated to 45C. A solution of tert-butyl nitrite (6.53 ml; 55.008 mmol) in MeCN (10 ml) was then added dropwise over 30 min., and the resulting mixture was further stirred at 45C for 2h20. The dark heterogeneous reaction mixture was allowed to cool to rt, and was directly purified by FC (DCM). After concentration to dryness under reduced pressure, the expected product 4-bromo-2-chloro-1-trifluoromethyl-benzene was obtained as a yellow oil (12.82O g; 50%). LC-MS: tR = 1.10 min.; [M+H]+: no ionisation. |
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