Cesium carbonate → 2-(4-((1R,2R)-2-((3-fluoro-4-(1H-tetrazol-1-yl)benzyloxy)methyl)cyclopropyl)piperidin-1-yl)-5-(methoxymethyl)pyrimidine

Participants

Reaction Conditions

Reaction Steps

4-((1R,2R)-2-((3-fluoro-4-(1H-tetrazol-1-yl)benzyloxy)methyl)cyclopropyl)piperidinium chloride (Step D product, 45 mg, 0.122 mmol) and 2-chloro-5-(methoxymethyl)pyrimidine (Intermediate 18, 22 mg, 0.136 mmol) were dissolved in DMF (600 uL), to which was added cesium carbonate (100 mg, 0.306 mmol). The reaction was heated at 55° C. overnight. The reaction mixture was cooled to rt and diluted with EtOAc (5 mL) and water (5 mL). The layers were cut and the aqueous phase extracted with EtOAc (5 mL×2). The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was loaded onto 2×2000 micron silica preparative TLC plates (uv 254 active) which were developed using 50% EtOAc/Hex as the solvent system. The desired silica (Rf=0.4 @ 50% EtOAc/Hex) was collected and extracted to give the title compound (32 mg, 57%). 1H NMR (500 MHz, CDCl3) δ 9.14 (s, 1H), 8.39 (s, 2H), 7.94 (t, 1H), 7.40 (dd, 2H), 4.73 (t, 2H), 4.65 (q, 2H), 4.29 (s, 2H), 3.61 (td, 2H), 3.38 (s, 3H), 2.95 (m, 2H), 1.95 (dd, 2H), 1.43 (m, 2H), 1.28 (m, 1H), 1.22 (m, 1H), 0.85-0.73 (m, 2H), 0.11 (q, 1H). LC/MS (m/z): 454 (M+H)+, GPR119 Human EC50: 1.1 nM.

Provenance & Evidence