Ammonia → HCID 68579792, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of rac-3-{4-[5-(2-dimethylamino-6-ethyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol (78 mg, 0.183 mmol) and DIPEA (47 mg, 0.365 mmol) in THF (5 mL) is added methanesulfonylchloride (23 mg, 0.201 mmol) at 0° C. The mixture is stirred at 0° C. for 3 h (Mesylate: LC-MS: tR=0.88 min; [M+1]+=505.12) before it is added to 7 N NH3 in methanol (10 mL). The mixture is stirred at 65° C. for 16 h. The solvent is removed in vacuo and the crude product is purified on prep. TLC plates with DCM containing 5% of methanol and 10% of 7 N NH3 in methanol to give rac-1-amino-3-{4-[5-(2-dimethylamino-6-ethyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phen-oxy}-propan-2-ol as a yellow resin. This material is dissolved in DCM and to the solution glycolic acid (29 mg, 0.375 mmol) and DIPEA (70 mg, 0.540 mmol) is added. The mixture is cooled to 0° C. before TBTU (71 mg, 0.221 mmol) is added. The mixture is stirred at 0° C. for 1 h before it is diluted with EA (100 mL), washed twice with sat. aq. NaHCO3-solution (25 mL), dried over Na2SO4, filtered and concentrated. The crude product is purified on prep. TLC plates with heptane:EA 7:3 to give rac-N-(3-{4-[5-(2-dimethylamino-6-ethyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide (32 mg) as a yellow resin; LC-MS: tR=0.76 min; [M+1]+=484.19.

Provenance & Evidence