Thiophene-2-carbohydrazide → Tofimilast

Participants

Reaction Steps

A solution of 1cyclopentyl-7-ethoxy-3-ethyl-4,5-dihydro-1H-pyrazolo[3,4-c]pyridine (3.739 kg, 14.3 moles) and 2thiophenecarboxylic hydrazide (2.237 kg, 15.8 moles) were heated in a solution in 1-butanol (37 L) to ˜90° C. in a 50 gal tank for 48 hours. At this point, some 1-butanol was distilled off to remove water azeotropically. The reaction was concentrated to a low volume and 4 gallons of methylene chloride (4 gal, 15 L) was added. The organics were washed twice with 1 N HCl (8 gal, 30.3 L) and concentrated by distillation to low volume. Isopropanol (16 L) was added to the concentrate and the resulting slurry was cooled and granulated. The product was collected by filtration and vacuum oven dried at 40° C. The yield was 3.25 kg (67%) of a white solid; mp 126° C.

Provenance & Evidence