N-Methylisopropylamine → 3-[2-Ethyl-4-(5-{5-[(isopropyl-methyl-amino)-methyl]-4-methyl-thiophen-2-yl}-[1,2,4]oxadiazol-3-yl)-6-methyl-phenyl]-propionic acid

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Reaction Steps

3-[2-Ethyl-4-(5-{5-[(isopropyl-methyl-amino)-methyl]-4-methyl-thiophen-2-yl}-[1,2,4]oxadiazol-3-yl)-6-methyl-phenyl]-propionic acid ethyl ester formate salt (86 mg) is obtained as a pale yellow oil starting from 3-{2-ethyl-4-[5-(5-formyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-propionic acid ethyl ester (100 mg, 0.242 mmol) and N-isopropyl-methylamine (709 mg, 9.70 mmol) using two portions of sodium triacetoxyborohydride (171 mg, 0.727 mmol) and following Method C; LC-MS: tR=0.71 min; [M+1]+=470.15; 1H NMR (D6-DMSO): δ1.05 (d, J=6.5 Hz, 6H), 1.17-1.26 (m, 6H), 2.23 (s, 6H), 2.39 (s, 3H), 2.44-2.50 (m, 2H), 2.72 (q, J=7.5 Hz, 2H), 2.89-3.01 (m, 3H), 3.70 (s, 2H), 4.10 (q, J=7.0 Hz, 2H), 7.69 (s, 2H), 7.80 (s, 1H), 8.15 (s, 1H). b) A solution of the above propionic acid ethyl ester (75 mg, 0.145 mmol) in ethanol (1.5 mL) and 2 N aq. NaOH (1.5 mL) is stirred at rt for 6 h. The ethanol is evaporated and the reaction mixture is acidified by adding formic acid before it is separated be prep. HPLC (column: Atlantis T3 C18, 30×75 mm, 10 μm, eluting with a gradient of acetonitrile in water containing 0.5% of formic acid) to give the title compound (62 mg) as its formate salt as a pale yellow solid; LC-MS*: tR=0.66 min; [M−1]−=440.02; 1H NMR (D6-DMSO): δ1.05 (d, J=6.5 Hz, 6H), 1.22 (t, J=7.3 Hz, 3H), 2.23 (s, 6H), 2.33-2.42 (m, 5H), 2.73 (q, J=7.5 Hz, 2H), 2.89-2.97 (m, 3H), 3.70 (s, 2H), 7.69 (s, 2H), 7.80 (s, 1H), 8.17 (s, 1H).

Provenance & Evidence