Regioselective alkylation of 2-alkyl-5,6,7,8-tetrahydro-3h-cycloheptimidazol-4-ones and 2-alkyl-3h-cycloheptimidazol-4-ones.
Regioselective alkylation of 2-alkyl-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-one (1) and 2-alkyl-3H-cycloheptimidazol-4-one (2) was investigated. 3-[2'-(1-tert-Butyl-1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-2-propyl-5,6,7,8-tetrahydro-1H-cycloheptimidazol-4-one (6) was preferentially obtained under the conditions by using NaH in DMF or THF. On the other hand, 3-[2'-(1-tert-butyl-1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-2-propyl-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-one (5), the synthetic intermediate compound of Pratosartan, was obtained selectively in the presence of n-Bu(4)NBr in toluene by using aqueous sodium hydroxide as a base. In this reaction, it was found that the concentration of the alkaline solution influences its regioselectivity. This selectivity was observed even for aldehyde and ester derivatives.
Sonegawa
Motoharu
M
Kotobuki Research Laboratories, Kotobuki Seiyaku Company Ltd., 6351 Sakaki-Machi, Nagano 389-0697, Japan. ktb-g121@kotobuki-pharm.co.jp
Yokota
Masayuki
M
Tomiyama
Hiroshi
H
Tomiyama
Tsuyoshi
T
D000478:Alkylation; D002384:Catalysis; D003508:Cycloheptanes / Q000737:chemistry*; D007093:Imidazoles / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D012996:Solutions; D012997:Solvents; D013055:Spectrophotometry, Infrared
D003508:Cycloheptanes; D007093:Imidazoles; D012996:Solutions; D012997:Solvents