Diisopropylethylamine → 3-[4-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidin-1-yl]-butyronitrile

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Reaction Conditions

Reaction Steps

A mixture of 1-benzenesulfonyl-4-chloro-5-nitro-1H-pyrrolo[2,3-b]pyridine (15.33 g, 45.4 mmol), 3-(4-amino-piperidin-1-yl)-butyronitrile (hydrochloride salt) (50.0 mmol), diisopropylethylamine (24.5 ml, 141 mmol) in propan-2-ol (200 ml) was heated at 80° C. for 18 h. The mixture was cooled to 25° C. and was concentrated to approximately 25 ml volume. This material was partitioned between water (200 ml) and CH2Cl2 (2×200 ml). The combined organic layers were dried over MgSO4, filtered, and the filtrate was concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel (gradient: 0 to 6% CH3OH in CH2Cl2) afforded 3-[4-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidin-1-yl]-butyronitrile (11.3 g, 53% over 3 steps) as a yellow-orange foam. LCMS (Method G, ESI): RT=0.70 min, m+H=469.3. This material was used in the next step below without additional characterization.

Provenance & Evidence