Water → HCID 66823764, compound

Participants

Reaction Steps

A suspension of 1,1-dimethylethyl 4-{4-amino-3-[1-(phenylacetyl)-2,3-dihydro-1H-indol-5-yl]thieno[3,2-c]pyridin-7-yl}-3,6-dihydro-1(2H)-pyridinecarboxylate (220 mg, 0.388 mmol) and Pd/C, 10 wt. % (dry basis), wet, Degussa type E101 NE/W, ca. 50% water (25 mg, 0.012 mmol) in Ethanol (10 mL) was stirred under an atmosphere of hydrogen for 2 hours. The starting material never seemed to go into solution (the mixture was a thick gray suspension), so Tetrahydrofuran (THF) (15 mL) was added. It was stirred under hydrogen for another 17 hr, then filtered. LCMS appeared to indicate little or no conversion (based on the mass of the peak). The filtrate was subjected to 10% Pd/C hydrogenation on an H-Cube® reactor at 40° C. and 40 bar for 23 hours (the actual reaction time was less because of an error on the H-cube which stopped the reaction sometime during the night). LCMS appeared to show mostly desired product along with some starting material and a smallish byproduct. It was concentrated in vacuo, and the residue was dry loaded onto silica gel (1 g) and purified by flash chromatography (Analogix, 40 g SiO2, DCM to 95/5/0.5 DCM/MeOH/NH4OH gradient over 42 minutes) to give 1,1-dimethylethyl 4-{4-amino-3-[1-(phenylacetyl)-2,3-dihydro-1H-indol-5-yl]thieno[3,2-c]pyridin-7-yl}-1-piperidinecarboxylate (91 mg) as an off-white solid.

Provenance & Evidence