Hydrochloric Acid → HCID 86646458, compound

Participants

Reaction Steps

To a suspension of 5-[5-(3-ethyl-4-hydroxy-5-methyl-phenyl)-[1,3,4]thiadiazol-2-yl]-3-methyl-thiophene-2-carbaldehyde (54 mg, 157 μmol) and K2CO3 (65 mg, 470 μmol) in acetonitrile (10 mL), (2-bromoethoxy)-tert.-butyl-dimethyl silane (66 mg, 274 μmol) is added. The mixture is stirred at 70° C. for 2 h before another portion of (2-bromoethoxy)-tert.-butyl-dimethyl silane (66 mg, 274 μmol) is added. Stirring is continued at 60° C. for 16 h. The mixture is cooled to rt, acidified by adding 1 N aq. HCl (2 mL) and stirred at rt for 10 min. The reaction mixture is concentrated to a volume of about 1 mL, is diluted with DMF (1.5 mL) and is then separated by prep. HPLC (XBridge Rp C18, 30×75 mm, eluting with a gradient of acetonitrile in water containing 0.5% of aq. ammonia) to give 5-{5-[3-ethyl-4-(2-hydroxy-ethoxy)-5-methyl-phenyl]-[1,3,4]thiadiazol-2-yl}-3-methyl-thiophene-2-carbaldehyde (33 mg) as a pale yellow resin; LC-MS: tR=0.69 min; [M+1]+=429.06. b) The title compound (24 mg) is obtained as a colourless resin starting from the above 5-{5-[3-ethyl-4-(2-hydroxy-ethoxy)-5-methyl-phenyl]-[1,3,4]thiadiazol-2-yl}-3-methyl-thiophene-2-carbaldehyde (33 mg, 85 μmol) and dimethylamine (46 mg, 340 μmol); LC-MS*: tR=0.96 min; [M+1]+=418.01; 1H NMR (D6-DMSO): δ1.22 (t, J=7.5 Hz, 3H), 2.20 (s, 3H), 2.25 (s, 6H), 2.34 (s, 3H), 2.74 (q, J=7.5 Hz, 2H), 3.58 (s, 2H), 3.72-3.77 (m, 2H), 3.85 (t, J=4.5 Hz, 2H), 4.92 (t, J=5.5 Hz, 1H), 7.52 (s, 1H), 7.67 (s, 2H).

Provenance & Evidence