3,5-BIS(TRIFLUOROMETHYL)-1,2-DIAMINOBENZENE

D. D. Example 100 Preparation of 6-tert-butyl-2-[2-chloro-4-(3-methylpyridin-2-yl)phenyl]-1H-benzoimidazole (0455) (0456) To a solution of 0.46 g (3.6 mmol) 2-chloro-3-methylpyridine in 20 mL 1, 2-dimethoxyethane and 20 mL distilled water were added 2.2 g (21.1 mmol) Na2CO3, 0.6 g (3.0 mmol) 3-chloro-4-carboxylphenylboronic acid and 50 mg Pd(PPh3)4, followed by stirring the solution for 15 hours in a heat flux condition and concentrating in a vacuum. The aqueous layer was washed with ethyl acetate and adjusted to a pH of 1 with conc. HCl. Thereafter, extraction with ethyl acetate was conducted many times and the organic layer was dried over magnesium sulfate and vacuum concentrated. The concentrate was dissolved in 25 mL dimethylformamide and mixed with 0.5 g (3.0 mmol) 4-tert-butylbenzene-1, 2-diamine, 1.2 mL (6.0 mmol) diisopropylethylamine and 1.3 g (7.2 mmol) O-(7-azabenzotriazol-1-yl)-N, N, N?, N?-tetramethyleuronium hexafluorophosphate, followed by stirring at room temperature for 16 hours. The concentrate obtained by vacuum concentration was dissolved in ethyl acetate, washed with saturated NaHCO3 and saturated NaCl, and dried over magnesium sulfate, followed by vacuum concentration. The residue thus obtained was dissolved in acetic acid/toluene (15 mL/1.5 mL), and the solution was stirred at 75 C. for 3 hours and vacuum concentrated. Again, this concentrate was dissolved in ethyl acetate, washed with saturated NaHCO3 and saturated NaCl, and dried over magnesium sulfate, followed by vacuum concentration. The residue was separated using column chromatography (developing solvent: chloroform/methanol=30/1) to produce 0.77 g of 6-tert-butyl-2-[2-chloro-4-(3-methylpyridin-2-yl)phenyl]-1H-benzoimidazole (yield 68%). (0457) 1H NMR (CDCl3) delta: 8.69 (d, 1H), 8.56-8.52 (m, 1H) 8.06 (s, 1H), 7.73 (s, 1H), 7.53-7.48 (m, 1H), 7.42-7.39 (m, 1H), 7.31-7.27 (m, 1H), 7.18-7.14 (m, 1H), 6.89 (d, 1H), 2.67 (s, 3H), 1.38 (s, 9H)(The same procedure as in (3) of was performed to produce Compounds 2 to 16.3) Preparation of 2-[4-(3-chloropyridin-2-yl)phenyl]-6-trifluoromethyl-1H-benzoimidazole (0292) 0.44 g (2.5 mmol) 4-trifluoromethylbenzene-1, 2-diamine, 1.0 mL (5.0 mmol) diisopropylethylamine and 1.1 g (6 mmol) O-(7-azabenzotriazol-yl)-N, N, N?, N?-tetramethyleuronium hexafluorophosphate were added to a solution of 0.59 g (2.5 mmol) 4-(3-chloropyridin-2-yl)benzoic acid in 25 mL dimethylformamide, which was then stirred at room temperature for 16 hours and vacuum concentrated. The concentrate thus obtained was dissolved in ethyl acetate, washed with saturated NaHCO3 and saturated NaCl, dried over magnesium sulfate, and concentrated in a vacuum. The residue was dissolved in acetic acid/toluene (15 mL/1.5 mL) and stirred at 75 C. for 3 hours, followed by vacuum concentration. Again, the concentrate was dissolved in ethyl acetate, washed with saturated NaHCO3 and saturated NaCl, dried over magnesium sulfate, and vacuum concentrated. The residue was separated using column chromatography (developing solvent: chloroform/methanol=30/1) to produce 0.77 g of 2-[4-(3-chloropyridin-2-yl)phenyl]-6-trifluoromethyl-1H-benzoimidazole (yield 82%).

Molecular Weight:244.14
XLogP3:2.3
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:8
Exact Mass:244.04351717
Monoisotopic Mass:244.04351717
Topological Polar Surface Area:52
Heavy Atom Count:16
Complexity:248
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes