反应详情

DIPEA (0.224 mL, 1.29 mmol) was added to 3,4-difluorobenzoic acid (0.068 g, 0.43 mmol) and TBTU (0.138 g, 0.43 mmol) in DCM (2 mL). The mixture was stirred at rt for 30 min. 1-((2S,3S)-3-Methyl-2-(methylamino)pentyl)azetidin-3-ol (Compound G2.1) (0.1 g, 0.43 mmol) in DCM (1 mL) was added and the resultant mixture was stirred at rt overnight. The mixture was washed with NaHCO3, filtered through a phase separator and concentrated under reduced pressure. The residue was purified by preparative HPLC to give the title compound (95 mg, 68%). Mixture of rotamers: 1H NMR (600 MHz, DMSO-d6) δ 0.61-0.74, 0.75-0.92, 0.97-1.09, 1.20-1.63, 2.33-2.45, 2.48-2.83, 3.11-3.23, 3.32-3.38, 3.39-3.53, 4.04-4.23, 5.14-5.31, 7.10-7.22, 7.28-7.41, 7.42-7.56, 7.56-7.70. Total number of protons: 24. HRMS (M+H)+: calculated 327.1884. found 327.1878. The compounds according to Examples 29.2-29.9 were prepared, from appropriate intermediates, by analogy with the method described for Example 29.1 hereinbefore.

1. washThe mixture was washed with NaHCO3
2. filtrationfiltered through a phase separator
3. concentrationconcentrated under reduced pressure
4. customThe residue was purified by preparative HPLC