[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][OH:9])=[CH:4][CH:3]=1.[H-].[Na+].CS(O[CH:17]1[CH2:20][N:19]([C:21]([N:23]2[CH2:29][CH2:28][CH2:27][N:26]([CH:30]3[CH2:33][CH2:32][CH2:31]3)[CH2:25][CH2:24]2)=[O:22])[CH2:18]1)(=O)=O>CS(C)=O.CCOC(C)=O>[CH:30]1([N:26]2[CH2:27][CH2:28][CH2:29][N:23]([C:21]([N:19]3[CH2:20][CH:17]([O:9][CH2:8][C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)[CH2:18]3)=[O:22])[CH2:24][CH2:25]2)[CH2:31][CH2:32][CH2:33]1To a stirred solution of (4-fluorophenyl)methanol (27 mg, 0.2 mmol) in DMSO (1.5 mL) was added NaH (8.5 mg, 0.2 mmol, 60% purity) at RT. The mixture was stirred for 1 h and a solution of 1 1-[(4-cyclobutyl-1,4-diazepan-1-yl)carbonyl]azetidin-3-yl methanesulfonate (33 mg, 0.1 mmol) in DMSO (0.5 mL) was added. The resulting mixture was stirred at 100° C. overnight, cooled to RT and diluted with EtOAc. The crude mixture and washed with water/brine; 1/1 solution, dried (Na2SO4), filtered and concentrated at reduced pressure. Purification by preparative HPLC provided the title compound as colourless oil (8 mg, 18%).
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