Hydrochloric Acid → HCID 22063854, compound

To a solution of 1-tert-butyl-3-methyl-5-(5-m-tolyl-1H-imidazol-4-yl)-1,3-dihydro-benzoimidazol-2-one (prepared as described previously, 100 mg, 0.277 mmol) in THF (1 mL) was added sodium hydride (12 mg of a 60% dispersion in mineral oil, 0.31 mmol). After 5 minutes, p-toluenesulfonyl chloride (58 mg, 0.31 mmol) was added, and the reaction was allowed to stir overnight. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate and concentrated in vacuo to afford 140 mg of tolylated imidazole as a 1:1 mixture of regioisomers which was taken up in 1 mL of trifluoroacetic acid and treated with 0.25 mL of methanesulfonic acid. The mixture was allowed to stir for 2 hours, then diluted with methylene chloride and cautiously neutralized with aqueous sodium bicarbonate solution. The methylene chloride phase was dried over anhydrous sodium sulfate and concentrated in vacuo to afford 120 of a mixture of 1-methyl-6-[1-(toluene-4-sulfonyl)-5-m-tolyl-1H-imidazol-4-yl]-1,3-dihydro-benzoimidazol-2-one and 1-methyl-6-[3-(toluene-4-sulfonyl)-5-m-tolyl-3H-imidazol-4-yl]-1,3-dihydro-benzoimidazol-2-one. The following reaction was carried out using a modification of the procedure found in Chan, D. M. T.; Monaco, K. L.; Wang, R—P.; Winters, M. P. Tetrahedron Lett 1998, 39, 2933–2936. A mixture of the tosylated imidazoles (100 mg, 0.22 mmol), 3-thiopheneboronic acid (55.8 mg, 0.44 mmol), Cu(OAc)2 (39.6 mg, 0.22 mmol), powdered molecular sieves (400 mg), triethylamine (60.8 μL, 0.44 mmol) in methylene chloride (1 mL) was stirred for three days. The mixture was poured on to a celite pad and the pad was eluted with ethyl acetate. The ethyl acetate was concentrated in vacuo to afford a tan solid that was taken up in THF (1 mL) and treated with concentrated aqueous HCl (1 mL). After 2 hours, the reaction was diluted with water and washed with diethyl ether. The aqueous phase was basified with aqueous ammonium hydroxide, then extracted with methylene chloride (2×40 mL). The methylene chloride was dried over anhydrous sodium sulfate and concentrated in vacuo to afford 65 mg of 3-methyl-1-thiophen-3-yl-5-(5-m-tolyl-3H-imidazol-4-yl)-1,3-dihydro-benzoimidazol-2-one. MS (M+1)=387.2

1. additionas a 1:1 mixture of regioisomers which
2. dry with materialThe methylene chloride phase was dried over anhydrous sodium sulfate
3. concentrationconcentrated in vacuo
4. customto afford
5. customThe following reaction
6. stirringwas stirred for three days
7. additionThe mixture was poured on to a celite pad
8. washthe pad was eluted with ethyl acetate
9. concentrationThe ethyl acetate was concentrated in vacuo
10. customto afford a tan solid that
11. waitAfter 2 hours
12. washwashed with diethyl ether
13. extractionextracted with methylene chloride (2×40 mL)
14. dry with materialThe methylene chloride was dried over anhydrous sodium sulfate
15. concentrationconcentrated in vacuo

ORD record

ord-a1afedc7323447d58e5cdca626072124

Source dataset

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07056918B2