Bis(2-Methoxyethyl)amine → HCID 68714954, compound

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Reaction Steps

Di-(2-methoxyethyl)amine (6 ml) was added to a solution of 4-bromobenzylbromide (5 g) in DMF (20 ml) at ambient temperature. After stirring at ambient temperature for 2 h, the mixture was partitioned between ethyl acetate and saturated sodium hydrogen carbonate solution. The organic phase was dried, the solvent removed under vacuum to yield a yellow oil which was purified by column chromatography using a 0 to 20% ethyl acetate/isohexane gradient to yield the title compound as a clear oil (4.83 g). MS (M+H)+302. 1H NMR (CDCl3) 2.72 (t, 4H), 3.3 (s, 6H), 3.45 (t, 4H), 3.64 (s, 2H), 7.21 (d, 2H), 7.41 (d, 2H). b) 2-[(Aminocarbonyl)amino]-5-{4-[(bis-(2-methoxyethyl)amino)methyl]phenyl}-thiophene-3-carboxamide A solution of N-(4-bromobenzyl)-2-methoxy-N-(2-methoxyethyl)ethanamide (1.6 g) in THF (15 ml) was cooled to −60° C. under argon. Butyl lithium (5 ml, 1.6M solution in hexane) was added dropwise and the mixture was stirred at −60° C. for a further 20 min Triisopropylborate (1.8 ml) was added before allowing the mixture to warm to room temperature. After stirring at room temperature for 3.5 h, the THF was removed under vacuum and DME (20 ml), water (2 ml) and 2-(aminocarbonyl)amino-5-bromo-thiophene-3-carboxamide (0.47 g) were added. The mixture was degassed by purging with argon and sonicating for 15 min, sodium hydrogen carbonate (0.445 g) and Pd(Ph3)4 (0.1 g) added and heated to 90° C. for 18 h under argon. The solvent was removed under vacuum and the residue was partitioned between 2N sodium hydroxide solution and DCM. The combined phases were filtered and the aqueous phase was taken to pH 7 by addition of 5N aqueous hydrochloric acid. A precipitate formed which was purified by preparative hplc to yield the product as a solid (0.01 g). MS (M+H)+407. 1H NMR (DMSO-D6) 2.62 (t, 4H), 3.19 (s, 6H), 3.39 (t, 4H), 3.61 (s, 2H), 6.87-6.95 (bs, 2H), 7.22-7.31 (m, 3H), 7.44 (d, 2H), 7.61-6.9 (m, 2H), 10.97 (s,1H).

Provenance & Evidence