C1C([N+]([O-])=O)=CC=C([Cl-][C:11]([O-])=[O:12])C=1.[CH:14]1([N:18]2[CH2:24][CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)[CH2:17][CH2:16][CH2:15]1.N1C=CC=CC=1.Cl.[NH:32]1[CH2:35][CH:34]([OH:36])[CH2:33]1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH:14]1([N:18]2[CH2:24][CH2:23][CH2:22][N:21]([C:11]([N:32]3[CH2:35][CH:34]([OH:36])[CH2:33]3)=[O:12])[CH2:20][CH2:19]2)[CH2:17][CH2:16][CH2:15]1To a stirred RT solution of 4-nitrophenylchloroformate (2.63 g, 13.05 mmol) in DCM (10 ml) was added drop wise a solution of 1-cyclobutyl-1,4-diazepane (1.83 g, 11.86 mmol) and pyridine (1.03 g, 13.05 mmol) in DCM (2 ml). The resulting mixture was stirred at RT for approximately 3 days. The solvent was evaporated in vacuo and the residue dissolved in MeOH/IPA (1:3, 40 ml). Azetidin-3-ol hydrochloride (1.3 g, 11.86 mmol) and DIPEA (3.37 g, 26.1 mmol) were added and the resulting mixture was heated to reflux (˜90° C.) overnight. After cooling to RT, the solvent was evaporated and the residue partitioned between DCM (40 ml) and 2M K2CO3 aq (20 ml). The organic layer was separated and the aq. phase re-extracted with DCM (20 ml). The combined organic phases were dried (Na2SO4), filtered and concentrated under reduced pressure. Purification by silica flash column chromatography (eluting with DCM/MeOH/NH3 90:10:1) provided the title compound as yellow solid (1.16 g, 39%).
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