反应详情

(R)-(5-{3-[4-(2,2-Dimethyl-[1,3]dioxolan-4-ylmethoxy)-3-methoxy-5-methyl-phenyl]-[1,2,4]oxadiazol-5-yl}-3-methyl-thiophen-2-ylmethyl)-diethyl-amine is prepared starting from 5-diethylaminomethyl-4-methyl-thiophene-2-carboxylic acid (30 mg, 130 μmol) and (R)-4-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-N-hydroxy-3-methoxy-5-methyl-benzamidine (36 mg, 117 μmol) according to Method A. After the coupling and cyclisation step, the reaction mixture is acidified by adding 35% aq. HCl and the reaction mixture is stirred at rt for 40 min. The mixture is neutralised by adding 25% aq. NH3 solution before it is separated by prep. HPLC to give the title compound (31 mg) as a resin; LC-MS: tR=0.52 min; [M+1]+=462.21; 1H NMR (D6-DMSO): δ1.03 (t, J=7.0 Hz, 6H), 2.22 (s, 3H), 2.32 (s, 3H), 2.58 (q, J=7.0 Hz, 4H), 3.41-3.50 (m, 2H), 3.73 (s, 2H), 3.74-3.81 (m, 1H), 3.84-3.89 (m, 1H), 3.89 (s, 3H), 4.03 (dd, J=9.8, 4.3 Hz, 1H), 4.59 (t, J=5.8 Hz, 1H), 4.84 (d, J=5.3 Hz, 1H), 7.44-7.47 (m, 1H), 7.49-7.52 (m, 1H), 7.81 (s, 1H).

1. customis separated by prep