Sodium hydride → tert-Butyl 4-[(6-{[2-(4-chlorophenyl)-7-oxothieno[2,3-d]pyridazin-6(7H)-yl]methyl}pyridin-2-yl)oxy]piperidine-1-carboxylate

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Reaction Steps

To a stirred solution of 2-(4-chlorophenyl)thieno[2,3-d]pyridazin-7(6H)-one (0.32 g, 1.22 mmol) in DMF (10 mL) was added 60% sodium hydride in oil (0.06 g, 1.34 mmol, 55%). Stirred for 10 minutes under N2 atmosphere before addition of tert-butyl 4-[(6-{[(methylsulfonyl)oxy]methyl}pyridin-2-yl)oxy]piperidine-1-carboxylate (crude product from step d) dissolved in DMF (10 mL). The resulting mixture was stirred for 18 hours at room temperature followed by prep-HPLC purification to give the product. Yield: 0.22 g (32% over two steps). 1H NMR (400 MHz, CDCl3) δ 8.19 (s, 1H), 7.60-7.64 (m, 2H), 7.40-7.51 (m, 4H), 6.75 (d, 1H, J=7.28 Hz), 6.54 (d, 1H, J=8.24 Hz), 5.47 (s, 2H), 4.90-4.99 (m, 1H), 3.58-3.70 (m, 2H), 2.94-3.04 (m, 2H), 1.73-1.82 (m, 2H), 1.47-1.60 (m, 2H), 1.39 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 162.9, 157.3, 155.1, 153.7, 152.5, 140.3, 139.5, 136.4, 136.1, 133.1, 131.2, 129.8, 128.3, 118.9, 114.2, 110.3, 79.7, 70.6, 55.7, 41.3, 30.8, 28.7.

Provenance & Evidence