Dabco → (R)-1-(3-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluoro-N-(1-methoxy-1-oxopropan-2-yl)phenylsulfonamido)propyl)-4-aza-1-azoniabicyclo[2.2.2]octane bromide

Participants

Reaction Conditions

Reaction Steps

To a solution of (R)-methyl 2-(N-(3-bromopropyl)-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenylsulfonamido)propanoate (110 mg, 0.14 mol) in MeCN (3 mL) was added DABCO (20 mg, 0.18 mol.). The reaction flask was heated at 60° C. for 3 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. Recrystallization of the residue from DCM/Et2O (1:5) gave (R)-1-(3-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluoro-N-(1-methoxy-1-oxopropan-2-yl)phenylsulfonamido)propyl)-4-aza-1-azoniabicyclo[2.2.2]octane bromide (118 mg, 99%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.33 (d, 2H), 7.17-7.18 (d, 1H), 7.11 (s, 1H), 6.82-6.87 (m, 2H), 6.48-6.55 (m, 4H), 4.51-4.55 (q, 1H), 3.86-3.92 (q, 2H), 3.75 (s, 3H), 3.70 (s, 3H), 3.63-3.66 (t, 8H), 3.38-3.43 (m, 2H), 3.22-3.24 (t, 6H), 2.15-2.34 (m, 2H), 1.52 (s, 6H), 1.50 (s, 3H).

Provenance & Evidence