N-(4-Chlorobenzyl)-2-(chloromethyl)-7-methyl-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxamide (Preparation 1, 134 mg) and (S)-(3R)-morpholin-3-yl(phenyl)methanol hydrochloride (Preparation 9, 111 mg) in DMF (3 mL) is treated with diisopropylethylamine (0.5 mL). The mixture is heated at 90° C. overnight. After cooling to room temperature, the solution is poured into ethyl acetate (75 mL) and washed with dilute pH 4 phosphate buffer (10 mL), dilute pH 7 phosphate buffer (10 mL), and brine (10 mL). The organic layer is dried (Na2SO4), filtered and concentrated under reduced pressure. The resulting residue is purified by flash column chromatography (methanol/CH2Cl2, 1-3%) and ethyl acetate-hexanes crystallization to afford 0.13 g of the title compound Physical characteristics. M.p. 129-134° C.; 1H NMR (400 MHz, DMSO-d6) δ 10.60, 8.67, 7.41-7.25, 5.33, 5.07, 4.54, 4.17, 3.88, 3.81, 3.73, 3.6, 3.5-3.4, 2.94, 2.6, 2.4-2.3; HRMS m/z 538.1561 (M+H)+. Anal. Found: C, 62.33; H, 5.25; N, 7.75.
