Methanol → 2-[1,4]diazepan-1-yl-1-(4,4,4-trifluoro-butyl)-1H-benzoimidazole dihydroiodide

Treat a solution of 4-[1-(4,4,4-trifluoro-butyl)-1H-benzoimidazol-2-yl]-[1,4]diazepane-1-carboxylic acid tert-butyl ester (1.80 g, 4.22 mmol) and methanol (15 mL) at 0° C. with 57% hydroiodic acid (3.79 g, 16.9 mmol). Stir at room temperature for 30 minutes, heat to 50° C. for two hours and then stir at room temperature overnight. Thin layer analysis (silica gel, ethyl acetate) indicates the presence of starting material. Add 57% hydroiodic acid (1.12 mL) and heat at 50° C. for two hours. Concentrate in vacuo to remove the methanol, dissolve the residue in methanol (10 mL) and add ether (total of 200 mL) to afford a white tacky precipitate. Decant the supernatant, add ether (200 mL) and stir to afford a cream colored solid. Collect the solid by vacuum filtration under nitrogen and dry in vacuo at 82° C. (0.2 Torr) overnight to afford 2.25 g of 2-[1,4]diazepan-1-yl-1-(4,4,4-trifluoro-butyl)-1H-benzoimidazole dihydroiodide, m.p. 206-208° C. Elemental Analysis: Calculated for C16H21F3N4.2HI: 33.01%C, 3.98%H, 9.62%N; Found 33.15%C, 3.87%H, 9.41%N.

1. temperatureheat to 50° C. for two hours
2. stirringstir at room temperature overnight
3. temperatureheat at 50° C. for two hours
4. concentrationConcentrate in vacuo
5. customto remove the methanol
6. dissolutiondissolve the residue in methanol (10 mL)
7. additionadd ether (total of 200 mL)
8. customto afford a white tacky precipitate
9. customDecant the supernatant
10. additionadd ether (200 mL)
11. stirringstir
12. customto afford a cream colored solid
13. customCollect the solid
14. filtrationby vacuum filtration under nitrogen
15. customdry in vacuo at 82° C. (0.2 Torr) overnight

ORD record

ord-491ef24b92b541439a60950178189d04

Source dataset

uspto-grants-2002_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06423704B1