149765-15-1

137281-08-4

149765-15-1

Step 3. Synthesis of N-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-2,2-dimethylpropanamide N-(4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-2-yl)-2,2-dimethylpropanamide (210 g, 0.90 mol), phosphorus oxychloride (POCl3, 828 g, 5.40 mol, 503 mL, 6.0 equiv), benzyltriethylammonium chloride (411 g, 1.80 mol), N,N- dimethylaniline (220 g, 231 mL, 1.80 mol) and acetonitrile (2.0 L) were mixed and heated to reflux for 40-60 min, the reaction was monitored by HPLC. Upon completion of the reaction, the solvent was evaporated on a rotary evaporator and the residue was carefully (note: exothermic and corrosive) added slowly to ice water (16 L). The pH was adjusted to 7 with solid sodium hydroxide (NaOH) and the resulting precipitate was collected by filtration. The precipitate was dried to give N-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-2,2-dimethylpropanamide (159 g, 70% yield, 100% HPLC purity). Retention time (tR): 5.37 min. 1H-NMR (DMSO-d6) δ 12.35 (broad single peak, 1H), 10.06 (broad single peak, 1H), 7.54 (quadruple peak, 1H), 6.52 (quadruple peak, 1H), 1.25 (single peak, 9H).