Acetic Acid → {4-[(S)-1-(4-Fluoro-benzylamino)-3-methyl-butyl]-thiazol-2-yl}-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amine

Participants

Reaction Steps

96 mg (0.2 mmol) [4-((S)-1-Amino-3-methyl-butyl)-thiazol-2-yl]-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amine trihydrochloride was suspended in tetrahydrofurane (3 ml). At room temperature under nitrogen 103 mg (0.8 mmol) N,N-diisopropyl ethyl amine was added and the reaction was stirred for 10 minutes. 28 mg (0.22 mmol) 4-fluorobenzaldehyde, 24 mg (0.4 mmol) acetic acid and 127 mg (0.6 mmol) sodium triacetoxyborohydride were added and the reaction was stirred at room temperature over night. 2N aqueous NaOH solution (6 ml) was added and the reaction was extracted twice with diethyl ether. The combined organic layers were washed with brine, dried over sodium sulphate, filtered and the solvent was evaporated under reduced pressure. The crude product was purified on silica gel with methylene chloride/methanol 19/1 yielding 48 mg (50%) of {4-[(S)-1-(4-fluoro-benzylamino)-3-methyl-butyl]-thiazol-2-yl}-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amine as a yellow solid. MS ISP (m/e): 480.1 (100) (M+H)+. 1H NMR (DMSO-D6, 250 MHz): δ (ppm)=10.37 (s, 1H), 7.89 (s, 1H), 7.65 (s, 1H), 7.34-7.31 (m, 3H), 7.24 (d, 1H), 7.13-7.02 (m, 4H), 6.67 (s, 1H), 3.77 (m, 4H), 3.69 (d, 1H), 3.53-3.49 (m, 3H), 2.14 (s, 3H), 1.59-1.51 (m, 3H), 0.85 (d, 3H), 0.78 (d, 3H).

Provenance & Evidence