C=O.[NH:3]1[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.[CH2:9](O)C.[Cl:12][C:13]1[CH:32]=[CH:31][C:16]([CH2:17][NH:18][C:19]([C:21]2[C:22]([OH:30])=[C:23]3[CH:29]=[CH:28][S:27][C:24]3=[N:25][CH:26]=2)=[O:20])=[CH:15][CH:14]=1>C(O)(=O)C>[Cl:12][C:13]1[CH:14]=[CH:15][C:16]([CH2:17][NH:18][C:19]([C:21]2[C:22]([OH:30])=[C:23]3[CH:29]=[C:28]([CH2:9][N:3]4[CH2:8][CH2:7][O:6][CH2:5][CH2:4]4)[S:27][C:24]3=[N:25][CH:26]=2)=[O:20])=[CH:31][CH:32]=1Formaldehyde (2.6 mL) is added to morpholine (2.7 mL) at 0° C. Ethanol (10 mL) is then added followed by addition of N-(4-chlorobenzyl)-4-hydroxythieno[2,3-b]pyridine-5-carboxamide (1.00 g) from Example No. 1. Acetic acid (2 mL) is added, and the reaction mixture is allowed to warm to rt and then refluxed for 18 h. Additional morpholine (2.7 mL) and formaldehyde (2.6 mL) are added and the reaction is refluxed for an additional 24 h. The reaction mixture is allowed to cool to room temperature and is then concentrated in vacuo. The residue is treated with 25% NaOH (20 mL). The aqueous layer is extracted with ethyl acetate (50 mL) then CHCl3 (60 mL). Methanol (30 mL) is added to the aqueous layer and it is extracted with CHCl3 (2×60 mL). This procedure is repeated 3 times. The combined organic layers are dried with MgSO4, filtered, and concentrated in vacuo. The resulting brown solid is purified by column chromatography (CH2Cl2/methanol, 98/2; 96/4) to yield a tan solid which is recrystallized from ethyl acetate/Et2O to yield 0.718 g (55%) of the title compound as an off-white solid.
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