To a solution of 2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidine-6-carbaldehyde (953 mg, 3.36 mmol) in DCE (50 mL) was added 4-azetidin-3-ylmorpholine (525 mg, 3.69 mmol), trimethyl orthoformate (3.67 mL, 33.58 mmol) and acetic acid (0.19 mL, 3.36 mmol). After stirring at room temperature for 2 h sodium triacetoxyborohydride (1.10 g, 5.03 mmol) was added and the resulting mixture stirred for a further 2 h. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge, washed with H2O/MeOH then eluted with 2 M NH3 in MeOH/DCM. The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, gradient 0:100 to 20:80) to give 2-chloro-4-morpholin-4-yl-6-(3-morpholin-4-yl-azetidin-1-ylmethyl)thieno[3,2-d]pyrimidine as a pale yellow solid (856 mg, 62%). LCMS (Method C): RT=2.77 min, [M+H]+ 410
