[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18](OC4C(F)=C(F)C(F)=C(F)C=4F)(=[O:20])=[O:19])=[CH:15][CH:16]=3)[CH:11]=[CH:10][N:9]=2)=[C:4]([O:33][CH3:34])[CH:3]=1.[S:35]1[CH:39]=[CH:38][N:37]=[C:36]1[NH2:40].C1COCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18]([NH:40][C:36]4[S:35][CH:39]=[CH:38][N:37]=4)(=[O:20])=[O:19])=[CH:15][CH:16]=3)[CH:11]=[CH:10][N:9]=2)=[C:4]([O:33][CH3:34])[CH:3]=1A vial was charged with perfluorophenyl 1-(4-chloro-2-methoxyphenyl)isoquinoline-6-sulfonate (INTERMEDIATE NNN) (82.4 mg, 0.160 mmol), thiazol-2-amine (17.60 mg, 0.176 mmol), and THF (799 μl) to give a clear, colorless solution. The vial was cooled in an ice-water bath for 10 min, then lithium bis(trimethylsilyl)amide (1M in THF) (335 μl, 0.335 mmol) was added drop wise. After 30 min, the mixture was warmed to room temperature and loaded onto a 5-g silica gel loading column with the aid of DCM. The column was dried under vacuum for 5 min then eluted onto a pre-equilibrated 12-g column with 0 to 10% MeOH/DCM to give 1-(4-chloro-2-methoxyphenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (54 mg, 0.125 mmol, 78% yield) as an off-white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm=13.21-11.96 (m, 1H), 8.73-8.62 (m, 1H), 8.52 (d, J=1.8 Hz, 1H), 8.17-8.02 (m, 1H), 7.85 (dd, J=1.9, 8.9 Hz, 1H), 7.75-7.66 (m, 1H), 7.36-7.25 (m, 3H), 7.18 (dd, J=2.0, 8.0 Hz, 1H), 6.85 (d, J=4.6 Hz, 1H), 3.67 (s, 3H); m/z (ESI) 432.2 (M+H)+.
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