Dimethylformamide → 5-iodo-N,N-bis(4-methoxybenzyl)pyrazolo[1,5-a]pyridine-3-carboxamide

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Reaction Steps

A 22 L round bottom flask was charged with 5-iodopyrazolo[1,5-a]pyridine-3-carboxylic acid (I-42) (200 g, 694.3 mmol), bis(4-methoxybenzyl)amine (182.2 g, 708.3 mmol), DMAP (42.4 g, 347.2 mmol), EDCI (146.4 g, 763.8 mmol) and DMF (3500 mL). The suspension was stirred at room temperature over 16 hours and a dark solution was obtained. HPLC showed no (I-42) remaining. 2-MethylTHF (4 L) and water (7 L) were added to the reaction mixture while keeping the batch temperature <25° C. The aqueous layer was separated and extracted with 2-methylTHF (4 L). The combined 2-methylTHF layers were washed with 0.25 N HCl (2×4 L), aqueous saturated NaHCO3 (4 L) and 10% brine (4 L). The 2-methylTHF layer was treated with carbon (20 g) and Na2SO4 (80 g). The solution was passed through a silica gel pad (400 g of silica gel 240-400 mesh) and the pad was washed with 2-MeTHF (3 L). The filtrate was concentrated under vacuum to give 5-iodo-N,N-bis(4-methoxybenzyl)pyrazolo[1,5-a]pyridine-3-carboxamide (I-43) as a solid. 1H NMR (500 MHz, CDCl3) δ 8.73 (d, 1 H), 8.17 (d, 1H), 7.86 (s, 1H), 7.22 (d, 4 H), 7.14 (dd, 1 H), 6.92 (d, 4 H), 4.68 (s, 4 H), 3.83 (s, 6 H).

Provenance & Evidence