To a solution of 2-((2-(1-methyl-4-nitro-1H-pyrazol-5-yl)-1,3-dioxan-5-yl)methyl)isoindoline-1,3-dione (317 mg, 0.793 mmol, intermediate 75) in MeOH (10 mL) and THF (10 mL) was added ammonium formate (300 mg, 4.76 mmol) and 10% Pd/C (300 mg, 0.28 mmol) and the mixture was heated at reflux for 2 hr. The mixture was quickly filtered whilst hot and the cake washed with DCM (50 mL) and EtOAC (50 mL). The solvent was removed under reduced pressure and the crude residue was dissolved in EtOAc (10 mL) and 5-amino-2-(2,6-difluorophenyl)thiazole-4-carboxylic acid (170 mg, 0.66 mmol) and N-methylmorpholine (0.4 mL, 1.89 mmol) were added. Propylphosphonic anhydride solution (50% wt in EtOAc, 0.32 mL, 0.695 mmol) was added dropwise and the reaction mixture was stirred at room temperature for 16 hr. The solvent was removed under reduced pressure and the residue purified via silica gel chromatography (0-5% 7 N NH3 in MeOH/DCM) to give a colourless solid. To a solution of this solid in EtOH (2 mL) was added hydrazine hydrate (64-65% solution, 2 mL) and the mixture was heated at 70° C. for 16 hr. After concentration under reduced pressure, MeOH was added to the residue and the solids filtered off. The filtrate was concentrated under reduced pressure. Purification via K—NH column (0-5% 7 N NH3 in MeOH/DCM) followed by preparative HPLC gave 173 as a colourless solid (18 mg, 17% over three steps). 1H NMR (400 MHz, CDCl3) δ 9.78 (s, 1H), 8.26 (s, 1H), 7.36-7.29 (m, 1H), 7.06-6.99 (m, 2H), 6.18 (s, 2H), 5.73 (s, 1H), 4.11 (d, J=11.2 Hz, 2H), 3.87 (s, 3H), 3.78 (d, J=11.2 Hz, 2H), 2.53 (s, 2H), 1.83 (q, J=7.6 Hz, 2H), 0.84 (t, J=7.6 Hz, 3H). Alkyl NH2 not observed. LCMS (ES+) m/z 479 (M+1).
