Glycolic Acid → HCID 23729264, compound

Participants

Reaction Steps

To a solution of rac-3-{4-[5-(4-isobutyl-5-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-3-methoxy-phenoxy}-propane-1,2-diol (400 mg, 0.956 mmol) and DIPEA (257 mg, 1.99 mmol) in THF (40 mL), methanesulfonylchloride (125 mg, 1.095 mmol) dissolved in THF (10 mL) is added at −10° C. The reaction is allowed to warm to rt and is stirred for 15 h. Another portion of methanesulfonylchloride (30 mg, 0.258 mmol) in THF (2 mL) and DIPEA (128 mg, 0.993 mmol) is added and stirring is continued for 24 h. The mixture is evaporated and the residue is dissolved in 7 N NH3 in MeOH (17 mL). The resulting solution is stirred at 70° C. for 5 h before it is evaporated. The remaining residue is dissolved in DMF (15 mL) and glycolic acid (110 mg, 1.45 mmol), DIPEA (257 mg, 1.99 mmol) and TBTU (370 mg, 1.15 mmol) is added. The mixture is stirred at rt for 5 h, evaporated and the residue is purified on prep. TLC plates with EA to give 2-hydroxy-N-(2-hydroxy-3-{4-[5-(4-isobutyl-5-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-3-methoxy-phenoxy}-propyl)-acetamide (135 mg) as colourless foam; LC-MS: tR=0.95 min, [M+1]=476.29; 1H NMR (D6-acetone): δ 7.92 (d, J=8.8 Hz, 1H), 7.71 (s, 1H), 7.57 (s br, 1H), 6.77 (d, J=2.3 Hz, 1H), 6.71 (dd, J=2.3, 8.8 Hz, 1H), 4.74-4.67 (m, 2H), 4.15-4.07 (m, 3H), 3.99 (d, J=5.0 Hz, 2H), 3.93 (s, 3H), 3.66-3.57 (m, 1H), 3.48-3.39 (m, 1H), 2.52 (d, J=7.0 Hz, 2H), 2.49 (s, 3H), 1.95 (hept, J=7.0 Hz, 1H), 0.95 (d, J=6.4 Hz, 6H).

Provenance & Evidence