[CH3:1][O:2][C:3]([C:5]1[NH:6][CH:7]=[C:8]([C:10]([OH:12])=O)[CH:9]=1)=[O:4].Cl.[O:14]1[CH2:20][CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.[CH2:21]1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:1]([O:2][C:3]([C:5]1[NH:6][CH:7]=[C:8]([C:10]([N:17]2[CH2:18][CH2:19][CH2:20][O:14][CH2:15][CH2:16]2)=[O:12])[CH:9]=1)=[O:4])[CH3:21]To 1H-pyrrole-2,4-dicarboxylic acid 2-methyl ester (291 mg) in DCM (18 mL) was added [1,4]oxazepane hydrochloride (236 mg), PyBroP (802 mg) and DIEA (878 μL). The mixture was stirred for 3 h at RT after which it was washed with saturated aqueous NaHCO3 solution and 1 N HCl. The organic phase was dried (MgSO4) and concentrated in vacuo. The residue was purified by flash column chromatography on silica (ethyl acetate) to provide 4-([1,4]oxazepane-4-carbonyl)-1H-pyrrole-2-carboxylic acid ethyl ester (533 mg). This material was used directly used in the next step although traces of phosphine oxide impurities resulting from the coupling reagent were still present.
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