FC(F)(F)[C:3]1[CH:4]=[C:5]([C:12]([OH:14])=[O:13])[CH:6]=[C:7]2[C:11]=1NN=[CH:8]2.Br[C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][CH:27]=1)[CH:24]=[N:23][C:22]([NH:28][CH3:29])=[CH:21]2.O.O.[OH-].[Li+].[CH3:34]O>>[CH3:29][NH:28][C:22]1[N:23]=[CH:24][C:11]2[C:7]([CH:8]=1)=[CH:6][C:5]([C:12]([O:14][CH3:34])=[O:13])=[CH:4][CH:3]=2.[CH3:29][NH:28][C:22]1[N:23]=[CH:24][C:25]2[C:20]([CH:21]=1)=[CH:19][C:18]([C:12]([OH:14])=[O:13])=[CH:27][CH:26]=2
Methyl 3-(methylamino)isoquinoline-6-carboxylate was prepared by a method analogous to that described in Step 3 of Intermediate 21, using 6-bromo-N-methylisoquinolin-3-amine. To the crude material (580 mg, 2.7 mmol) was added water (5 mL), methanol (5 mL), and lithium hydroxide monohydrate (300 mg, 7 mmol). The mixture was stirred at room temperature overnight. The reaction was concentrated and the residue was acidified to pH=5 with 1 N aqueous hydrochloric acid. The resulting residue was dried under vacuum and purified by reversed-phase HPLC to give the title compound (512 mg, 89%) as a white solid. 1H NMR (400 MHz, CD3OD, δ): 8.81 (s, 1H), 8.23 (s, 1H), 7.80 (d, 1H), 7.72 (d, 1H), 6.70 (s, 1H), 2.93 (s, 3H).
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