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Structure of 1645-65-4
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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. : | 1645-65-4 |
Formula : | C8H4F3NS |
M.W : | 203.18 |
SMILES Code : | FC(C1=CC=C(N=C=S)C=C1)(F)F |
MDL No. : | MFCD00039645 |
InChI Key : | DQEVDFQAYLIBRD-UHFFFAOYSA-N |
Pubchem ID : | 137134 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H314-H334 |
Precautionary Statements: | P261-P280-P305+P351+P338-P310 |
Class: | 8 |
UN#: | 3261 |
Packing Group: | Ⅱ |
* 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 |
---|---|---|
Example 63 4-Methoxy-N-phenyl-3-[3-(4-trifluoromethyl-phenyl)-thioureido]-benzamide Prepared according to the procedure described for Example 60 using 3-amino-4-methoxy-N-phenyl-benzamide (0.198 g, 0.82 mmol) and 4-(trifluoromethyl)phenyl isothiocyanate (0.169 g, 0.83 mmol) to give the product (0.306 g); m.p. 194-196 C. Calculated for C22H18F3N3O2S: C, 59.32; H, 4.07; N, 9.43. Found: C, 59.04; H, 4.05; N, 9.35. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | EXAMPLE 69 Preparation of {1-Methyl-5-[2-(5-trifluoromethyl-1H-imidazol-2-yl)-pyridin-4-yloxy]-1H-benzoimidazol-2-yl}-(4-trifluoromethyl-phenyl)-amine 4-Trifluoromethylphenyl isothiocyanate (200 mg, 1 mmol) was added to a mixture of 4-(2-(5-(trifluoromethyl)-1H-imidazol-2-yl)pyridin-4-yloxy)-N1-methylbenzene-1,2-diamine (350 mg, 1 mmol) in 3 mL of acetonitrile. The reaction was stirred for 20 min at ambient temperature and was monitored by HPLC. Triethylamine (0.3 mL, 2.2 mmol) was added followed by 2-chloro-1-methylpyridinium iodide (270 mg, 1.05 mmol). The reaction mixture was heated to 50 C. for 5 h. The heating was stopped and 1.5 mL of water was added. After stirring the mixture for 2 h, the solid was collected by filtration and washed with 2:1 acetonitrile/water (3*1 mL) to afford 317 mg (61%) of the title compound. | |
EXAMPLE 70 Preparation of {1-Methyl-5-[2-(5-trifluoromethyl-1H-imidazol-2-yl)-pyridin-4-yloxy]-1H-benzoimidazol-2-yl}-(4-trifluoromethyl-phenyl)-amine 4-Trifluoromethylphenyl isothiocyanate (200 mg, 1 mmol) was added to a mixture of 4-(2-(5-(trifluoromethyl)-1H-imidazol-2-yl)pyridin-4-yloxy)-N1-methylbenzene-1,2-diamine (350 mg, 1 mmol) in 3 mL of acetonitrile. After stirring for 20 min at ambient temperature, HPLC analysis showed complete conversion. A mixture of thiourea (553 mg, 1 mmol) in POCl3 (3 mL) was stirred at ambient temperature. After 4 h, the mixture was heated to approximately 50 C. After heating for 2 h and monitored by HPLC, the title compound was provided. | ||
4-(Trifluoromethyl)phenyl isothiocyanate (23.37 g, 115 mmol) was added to a stirring solution of Ij (40.17 g, 115 mmol) in MeOH (460 mL) at it. The reaction was maintained at rt for 16 h. After the reaction was judged complete, a solution of FeCk (20.52g, 126.5 mmol) in MeOH (50 mL) was added to the reaction and the resulting mixture was stirred at rt overnight. The crude reaction mixture was added to a 3 L separatory funnel containing EtOAc (750 mL) and water (750 mL). The layers were separated, and the aqueous phase was extracted with EtOAc (aqueous phase saved). The organic layers were combined, washed with saturated aqueous Na2CO3 solution, water, and brine, then dried (MgSO4), and concentrated. The saved aqueous phase was made basic (pH = 10) by addition of saturated aqueous Na2COa solution and the resulting slurry was added to a 3 L separatory funnel containing EtOAc (500 mL). The mixture was agitated and the resulting emulsion was filtered through filter paper, and the layers were then separated and the aqueous phase was extracted with EtOAc (2 x 500 mL). The organic layers were combined, washed with brine, then dried (MgSO4), added to previously extracted material and concentrated. The combined product was triturated with CH2CI2 (500 mL), adsorbed onto S1O2 and purified by flash chromatography. A final trituration of material with CH2CI2 produced the compound of Formula I as a pure, white solid. LCMS m/z 519.1 (MH+); 1HNMR (300 MHz, CDCl3) delta 8.44 (d, J = 5.5 Hz, 1 H), 7.75 (d, J = 8.8 Hz, 2H), 7.61 (dd, J = 2.2, 8.5 Hz, 1 H), 7.59 (d, J = 8.8 Hz, 2 H), 7.56 (d, J = 2.5 Hz, 1 H), 7.38 (app d, J - 8.5 Hz, 1 H), 7.23 (d, J = 1.9 Hz, 1 H), 6.96 (dd, J = 2.2, 8.5 Hz, 1 H), 6.93 (dd, J = 2.5, 5.5 Hz, 1 H), 3.76 (s, 3 H); LCMS m/z = 519.0, tR = 2.57 min (MH+); Anal, calc'd for C24Hi6F5N6O: C 55.6, H 3.11, N 16.21; Found: C 55.81, H 3.43, N 16.42; mp: 217 - 2200C (dec). |
Step 7; 4-(Trifluoromethyl)phenyl isothiocyanate (23.37 g, 115 mmol) was added to a stirring solution of Ij (40.17 g, 115 mmol) in MeOH (460 mL) at rt. The reaction was maintained at <n="31"/>rt for 16 h. After the reaction was judged complete, a solution OfFeCl3 (20.52g, 126.5 mmol) in MeOH (50 mL) was added to the reaction and the resulting mixture was stirred at rt overnight. The crude reaction mixture was added to a 3 L separatory funnel containing EtOAc (750 mL) and water (750 mL). The layers were separated, and the aqueous phase was extracted with EtOAc (aqueous phase saved). The organic layers were combined, washed with saturated aqueous Na2CO3 solution, water, and brine, then dried (MgSO-O, and concentrated. The saved aqueous phase was made basic (pH = 10) by addition of saturated aqueous Na2CO3 solution and the resulting slurry was added to a 3 L separatory funnel containing EtOAc (500 mL). The mixture was agitated and the resulting emulsion was filtered through filter paper, and the layers were then separated and the aqueous phase was extracted with EtOAc (2 x 500 mL). The organic layers were combined, washed with brine, then dried (MgSO-O, added to previously extracted material and concentrated. The combined product was triturated with CH2Cl2 (500 mL), adsorbed onto SiO2 and purified by flash chromatography. A final trituration of material with CH2Cl2 produced the compound of Formula I as a pure, white solid. LCMS m/z 519.1 (MH+); 1H NMR (300 MHz, CDCl3) delta 8.44 (d, J= 5.5 Hz, 1 H), 7.75 (d, J- 8.8 Hz, 2H), 7.61 (dd, J= 2.2, 8.5 Hz, 1 H), 7.59 (d, J = 8.8 Hz, 2 H), 7.56 (d, J= 2.5 Hz, 1 H), 7.38 (app d, J= 8.5 Hz, 1 H), 7.23 (d, J= 1.9 Hz, 1 H), 6.96 (dd, J== 2.2, 8.5 Hz, 1 H), 6.93 (dd, J= 2.5, 5.5 Hz, 1 H), 3.76 (s, 3 H); LCMS m/z = 519.0, *R = 2.57 min (MH+); Anal, calc'd for C24H16F6N6O: C 55.6, H 3.11, N 16.21; Found: C 55.81, H 3.43, N 16.42; mp: 217 - 2200C (dec). | ||
Step 7; Ij <n="61"/>4-(Trifluoromethyl)phenyl isothiocyanate (23.37 g, 115 mmol) was added to a stirring solution of Ij (40.17 g, 115 mmol) in MeOH (460 mL) at rt. The reaction was maintained at rt for 16 h. After the reaction was judged complete, a solution Of FeCl3 (20.52g, 126.5 mmol) in MeOH (50 mL) was added to the reaction and the resulting mixture was stirred at rt overnight. The crude reaction mixture was added to a 3 L separatory funnel containing EtOAc (750 mL) and water (750 mL). The layers were separated, and the aqueous phase was extracted with EtOAc (aqueous phase saved). The organic layers were combined, washed with saturated aqueous Na2CO3 solution, water, and brine, then dried (MgSO4), and concentrated. The saved aqueous phase was made basic (pH = 10) by addition of saturated aqueous Na2CO3 solution and the resulting slurry was added to a 3 L separatory funnel containing EtOAc (500 mL). The mixture was agitated and the resulting emulsion was filtered through filter paper, and the layers were then separated and the aqueous phase was extracted with EtOAc (2 x 500 mL). The organic layers were combined, washed with brine, then dried (MgSO4), added to previously extracted material and concentrated. The combined product was triturated with CH2Cl2 (500 mL), adsorbed onto SiO2 and purified by flash chromatography. A final trituration of material with CH2Cl2 produced the compound of Formula I as a pure, white solid. LCMS m/z 519.1 (MH+); 1H NMR (300 MHz, CDCl3) delta 8.44 (d, J= 5.5 Hz, 1 H), 7.75 (d, J= 8.8 Hz, 2H), 7.61 (dd, J= 2.2, 8.5 Hz, 1 H), 7.59 (d, J= 8.8 Hz, 2 H), 7.56 (d, J= 2.5 Hz, 1 H), 7.38 (app d, J = 8.5 Hz, 1 H), 7.23 (d, J= 1.9 Hz, 1 H), 6.96 (dd, J= 2.2, 8.5 Hz, 1 H), 6.93 (dd, J= 2.5, 5.5 Hz, 1 H), 3.76 (s, 3 H); LCMS m/z = 519.0, tR = 2.57 min (MH+); Anal, calc'd for C24Hj6F6N6O: C 55.6, H 3.11, N 16.21; Found: C 55.81, H 3.43, N 16.42; mp: 217 - 22O0C (dec). | ||
4-Trifluoromethylphenyl isothiocyanate (5) was added to a stirred suspension of 4 in acetonitrile. The reaction mixture was stirred until deemed complete by HPLC and then filtered. The filtrate was treated with JV,iV-diisopropylethylamine and 2-chloro-l,3- dimethylimidazolinium chloride (DMC) until addition of lambdayV-diisopropylethylamine and DMC was complete. The reaction mixture was heated until deemed complete by HPLC and filtered through a 0.2 mum filter. Water was added to the reaction mixture and then cooled. The title compound was filtered and washed with an acetonitrile/water solution and dried under vacuum until a constant weight was obtained. The product was dissolved in a suffcient amount of refluxing ethanol to acheive a homogeneous solution. The title compound was crystallized out of solution by removal of ethanol by distillation. After distillation of ethanol, the resultant slurry was treated with water and the solution cooled. The solid product was was filtered, washed with ethanol/water and dried under vacuum until constant weight to give the product title compound as an off-white to yellow/brown solid. |
Tags: 1645-65-4 synthesis path| 1645-65-4 SDS| 1645-65-4 COA| 1645-65-4 purity| 1645-65-4 application| 1645-65-4 NMR| 1645-65-4 COA| 1645-65-4 structure
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