Methanesulfonyl chloride → HCID 59853059, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 3-(4-(2-fluoro-4-nitrophenoxy)pyridin-3-yl)prop-2-yn-1-ol (43 mg, 0.15 mmol) and DIPEA (45 μL, 0.26 mmol) in anhydrous THF (1.5 mL) was cooled to 0° C. and treated with methanesulfonyl chloride (15 mg, 0.11 mmol) in portions. After stirring at 0° C. for 1 h, the mixture was concentrated under reduced pressure. The residue was treated with DMF (1.0 mL), DIPEA (45 μL, 0.26 mmol) and azetidin-3-ylmethyl-carbamic acid tert-butyl ester (Beta Pharma Inc., 145 mg, 0.78 mmol) and stirred at rt for 2 h. The reaction mixture was partitioned between EtOAc and saturated aq. NaHCO3 solution and the EtOAc phase separated, washed with brine dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography on SiO2 eluting with 1-5% MeOH/CH2Cl2 to afford the title compound (33 mg, 48%) as a colorless oil. 1H NMR (DMSO-d6) δ 8.74 (s, 1H), 8.51 (d, 1H, J=5.6 Hz), 8.41 (dd, 1H, J=10.7, 2.5 Hz), 8.15 (d, 1H, J=9.2 Hz), 7.53 (t, 1H, J=8.6 Hz), 7.09 (d, 1H, J=6.1 Hz), 6.86 (t, 1H, J=5.6 Hz), 3.39 (s, 2H), 3.24-3.14 (m, 2H), 3.07-2.98 (m, 2H), 2.94-2.87 (m, 2H), 2.37-2.26 (m, 1H), 1.33 (s, 9H); MS(ESI+): m/z 401.20 (100), [(M-C4H9)]+; m/z 457.20 (25), (M+H)+.

Provenance & Evidence