Diisopropylethylamine → (3-(4-((3-(Difluoromethyl)azetidin-1-yl)methyl)phenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone

Participants

Reaction Steps

To a suspension of 68A (0.20 g, 0.57 mmol) in DCM (3 mL) was added 68C (0.25 g, 1.72 mmol) followed by DIPEA (0.30 mL, 1.72 mmol). Sodium triacetoxyborohydride (0.24 g, 1.15 mmol) was added. The mixture was stirred at RT for 5 h and then diluted with DCM. The solution was washed with an aqueous solution of NaHCO3 and then filtered through a phase separator. The solvent was removed by evaporation. The product was purified on a silica gel column using 1-4% methanol in DCM where the methanol contained 2M ammonia. The product was triturated from ether and after drying in the hood there was obtained 47 mg (19%) of 68 as a solid. 1H NMR (500 MHz, CDCl3): δ 2.86 (m, 1H), 3.19 (m, 2H), 3.36 (m, 2H), 3.55 (s, 2H), 4.34 (dd, 1H), 4.64 (dd, 1H), 4.78 (dd, 1H), 5.07 (m, 1H), 5.11 (m, 1H), 5.99 (t, 1H), 6.74 (d, 2H), 7.22 (d, 2H), 7.54 (t, 2H), 7.59 (t, 1H), 8.16 (d, 2H), MS (APCI+) m/z 441 [M+H]+, LC purity: 90%. A sample of (3-(4-((3-(difluoromethyl)azetidin-1-yl)methyl)phenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone was recrystallised from DCM/Et2O had m. p. 147° C. (purity 99%).

Provenance & Evidence