N-(6-CHLORO-PYRIDIN-2-YL)-2,2-DIMETHYL-PROPIONAMIDE

To a suspension of 6-chloro-pyridin-2-ylamine 13-1 (0.30 g, 2.33 mmol) and triethlyamine (0.41 mL, 2.92 mmol) in anhydrous methylene chloride at 0 °C was added a solution of trichloromethylacetyl chloride (0.32 mL, 2.57 mmol) in anhydrous methylene chloride. The mixture was stirred at 0 °C for 50 min, before allowing it to gradually warm up to room temperature. After 5 h, the reaction mixture was poured into water and the organic phase separated. The aqueous layer was extracted with methylene chloride and the combined organic phases were dried and concentrated. The product was purified by flash chromatography using Combiflashl-({4-[([l, 3]Oxathiolo[5, 4-c]pyridin-6-ylmethyl)amino]-l- piperidinyl} methyl)- 1 , 2-dihydro-4H, 9H-imidazo [1 , 2, 3-ij ] -1 , 8-naphthyridine-4, 9- dione hydrochloride; (a) λ/-(6-Chloro-2-pyridinyl)-2, 2-dimethylpropanamide; A solution of 6-chloro-2-pyridinamine (13.776g, 107 mmol) in toluene (100ml) and triethylamine (16.28ml, 118 mmol) at 50To a solution of 2-amino-6-chloropyridine (10.7 g, 83.5 mmol) in toluene (103 mL) NaHCO3 (14 g, 167 mmol) and pivaloyl chloride (15.4 mL, 125.2 mmol) were added at 0°C. The resulting mixture was stirred at room temperature for 5 hours then the suspension was filtered and the solid was washed with DCM. The filtrates were concentrated undervacuum then heptane (22 mL) was added and the resulting mixture was concentrated. The solid was filtered, washed with heptane (15 mL) and dried under vacuum to afford the title intermediate (15.4 g, 72.4 mmol, 87percent yield). LC-MS (M-H) = 213.2Synthesis of compound 3[0120] Pivaloyl chloride (18.7 mL, 151.6 mmol) was slowly added to an ice-cooled solution of 6-chloropyridin-2-amine (15 g, 116.7 mmol) and triethylamine (24.25 mL, 124.96 mmol) in DCM (180 mL). The mixture was stirred in an ice-bath for 15 min and then at rt for 6 h. The mixture was poured into water. The organic layer was washed with saturated aq NaHC0To a solution of 10.1 (7.0 g, 54.54 mmol, 1.0 equiv) and pivaloyl chloride (6.7 mL, 57.0 mmol, 1.05 equiv) in toluene was added EtExample 22