To a microwave vial charged with 1-chloro-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (Intermediate GG; 3.00 g, 9.35 mmol), 2-fluoro-5-picoline-3-boronic acid (1.469 ml, 12.16 mmol), potassium carbonate (6.46 g, 46.8 mmol) and Pd(Ph3P)4 (1.081 g, 0.935 mmol) was added Dioxane (46.8 ml) and Water (15.59 ml) and heated thermally to 120° C. After 3 hrs LC-MS indicated about 40% conversion with starting material present. Additional boronic acid was added (1 g) and heating continued at 120° C. for 4 hrs affording ˜75% conversion. The mixture was allowed to stir at room temperature over the 3 days under nitrogen afford little to no further conversion. Additional boronic acid (500 mg) and Pd(PPh3)4 (500 mg) was added and the mixture heated back to 120° C. for 3 hr affording near complete conversion according to LC-MS. The mixture was cooled to room temperature, transferred to a seperatory funnel, diluted with water and extracted with EtOAc but the material stayed in the aqueous phase, although this wash did remove many impurities (including PPh3O). The aqueous was washed with DCM, but again the material stuck in the aqueous phase. The aqueous was acidified to ˜pH 2 affording a precipitate which was collected as a brown solid, fairly clean product by LC-MS (300 mg). The aqueous was dried to near dryness affording a precipitate which was collected but was mostly salts with some product. The solid and filtrate were combined and silica gel added and the mixture dried under reduced pressure. The material was purified with a 100 g ultra snap column ramping MeOH in DCM (0-50%) affording product (only 400 mg) as a light yellow solid. Much of the material had remained on the dry pack. The dry packed slurry was purified 2× (split into two parts) by loading directly onto a KP-C18-HS 60 g Biotage column using the reverse phase MPLC ramping IPA in H2O (with 1% NH4OH) (0-100%) affording 1 g of product as a brown solid, in total (1.4 g, 38%). m/z (ESI) 396.2 (M+H)+
