[CH2:1]([O:3][C:4]([C:6]1([C:15]([OH:17])=O)[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7]1)=[O:5])[CH3:2].N[C:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21][N:20]=1.CC[N:31](C(C)C)C(C)C.CO.C(Cl)Cl>C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1([C:15](=[O:17])[NH:31][C:24]2[CH:25]=[CH:26][CH:27]=[C:28]3[C:23]=2[CH:22]=[CH:21][N:20]=[CH:19]3)[CH2:7][C:8]2[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:14]1)=[O:5])[CH3:2]A 25 mL reaction vial which contains a stirring bar is charged with indane-2-carboxylic acid ethyl ester (205, 1.0 g, 4.27 mmol) and dry DCM (15 mL). Stirring is initiated. After dissolution is complete, the HTBU (1.62 g, 4.27 mmol) is added. After 5 min, the 5,-aminoisoquinoline. (616 mg, 4.27 mmol) is added followed by DIPEA (1.72 mL, 9.8 mmol). The reaction is allowed to stir for 63 h. Analysis by tlc of the reaction mixture (silica, 10% MeOH/DCM) indicates complete consumption of the starting acid. The contents of the reaction flask are transferred to a reparatory funnel and diluted with EtOAc (40 mL). The organic phase is washed consecutively with dilute aqueous HCl (3%, 20 mL), saturated aqueous NaHCO3 (20 mL) and brine (20 mL), and then dried over MgSO4, filtered and evaporated in vacuo to provide 3.13 g of light orange solid. This material is dissolved in 15 mL of DCM. This material is purified utilizing an ISCO Companion with a 40 g cartridge of silica. The gradient is 10% EtOAC in heptanes over 4 column volumes followed by a linear gradient to 90% EtOAc over 12 column volumes. 17 mL fractions of eluent are collected. Fractions 17 through 31 are combined and evaporated in vacuo. This gives white solid (1.39 g, 90%).
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