4-Methylmorpholine → (S)-N-(1-Cyclopropyl-2-(3-cyclopropyl-3-hydroxyazetidin-1-yl)ethyl)-4-fluoro-N,3-dimethylbenzamide

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Reaction Steps

4-Fluoro-3-methylbenzoic acid (0.102 g, 0.66 mmol), TBTU (0.248 g, 0.77 mmol) and NMM (0.063 mL, 0.58 mmol) was mixed in DCM (10 mL). After 10 min at rt was (S)-3-cyclopropyl-1-(2-cyclopropyl-2-(methylamino)ethyl)azetidin-3-ol (Compound L2) (0.116 g, 0.55 mmol) added. The resultant mixture was stirred at rt for 48 h. To the mixture was 1.4 N KOH (5 mL) added. The organic phase was isolated, filtered through a phase separator and concentrated under reduced pressure. The residue was purified by preparative HPLC to give the title compound (96 mg, 50%). Mixture of rotamers: 1H NMR (600 MHz, DMSO-d6) δ 0.09-0.14, 0.22-0.70, 1.01, 1.18, 2.30, 2.52-2.55, 2.72-3.10, 3.20, 3.72, 5.12, 7.15-7.44. Total no of protons: 27. HRMS (M+H)+: calculated 347.2135. found 347.2124.

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