Triethylamine → HCID 22741883, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(dimethylamino)ethyl 4-chloro-3-nitrobenzoate (2.5 g, 9.1 mmol) and 2d (2.0 g, 9.1 mmol) in anhydrous NMP (5 ml) was added triethylamine (1.3 ml, 9.1 mmol), and the mixture was stirred at 80° C. for 4 hours. The cooled mixture was poured into ice-water (100 ml) and extracted with ethyl acetate (4×20 ml). The combined organic extracts were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column-chromatography on silica gel using a mixture of dichloromethane and methanol (9:1 v/v) as the eluent to yield 2-(dimethylamino)ethyl 3-nitro-4-(3-(1-acetylpiperazin-4-yl)anilino)benzoate (1 g, 24%). This intermediate product was dissolved in ethanol (50 ml) and was hydrogenated quantitatively at ambient pressure, using Pd (5% on activated carbon) as the catalyst. The resulting diamine was dissolved in THF (50 ml) and triethyl orthoformate (0.7 ml, 4.2 mmol) was added, together with a catalytic amount of pTSA. The mixture was heated to reflux for 1 hour. The solvent was removed under reduced pressure and the residue was partitioned between aqueous sodium carbonate (1M) and ethyl acetate. The organic phase was dried over sodium sulfate and concentrated under reduced pressure, and the residue was chromatographied on silica gel using a mixture of dichloromethane, methanol and aqueous ammonia (90:10:1) as the eluent. The product isolated from the eluate was treated with activated carbon in refluxing ethanol and the product thus obtained was triturated with petroleum ether to yield 4i (0.18 g, 20%). M.p. 101-103° C.

Provenance & Evidence