Acetic Acid → methyl 6-cyclohexyl-5-[3-({[2-(diethylamino)ethyl]amino}methyl)-2-thienyl]-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate

Participants

Reaction Steps

Methyl 6-cyclohexyl-5-(3-formyl-2-thienyl)-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate and N,N-diethylaminoethylamine (10 eq.) were dissolved in THF (0.08 M) and the pH adjusted with AcOH to 6; the solution was left stirring for 4 h, then all volatiles were evaporated i. vac. The residual oil was dissolved in MeOH (0.08M), NaCNBH3 (4 eq.) was added, and the mixture was stirred overnight at RT to give methyl 6-cyclohexyl-5-[3-({[2-(diethylamino)ethyl]amino}methyl)-2-thienyl]-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate. Under the reaction conditions the latter partially closed to afford methyl 12-cyclohexyl-5-[2-(diethylamino)ethyl]-6-oxo-4,5,6,7-tetrahydrothieno[2,3-f]thieno[2′,3′:4,5]pyrrolo[1,2-d][1,4]diazocine-10-carboxylate; to drive this reaction to completion a catalytic amount of NaOMe was added and stirring was continued at 40° C. for 4 days. To a 0.05M solution of the foregoing amide in dry THF a 2M solution of borane-dimethylsulfide complex (13 eq.) in THF was added and the mixture was stirred for 1 h; after evaporation of all volatiles the residue containing (methyl 12-cyclohexyl-5-[2-(diethylamino)ethyl]-4,5,6,7-tetrahydrothieno[2,3-f]thieno[2′,3′:4,5]pyrrolo[1,2-d][1,4]diazocine-10-carboxylate) was suspended in MeOH (0.03M) and water. The pH was adjusted with LiOH to 9. The solution was left stirring at RT. Then an excess of 1N KOH-solution was added and the mixture was warmed to 50° C. and stirred for 2 h; the title compound (24%) was isolated by prep RP-HPLC. 1H-NMR (400 MHz, DMSO-d6, 330 K, δ) 7.67 (d, 1H, J 5.1), 7.18 (d, 1H, J 5.1), 3.15-3.12 (m, 2H), 3.09-3.05 (m, 5H), 2.87-2.81 (m, 2H), 1.79-1.63 (m, 8H), 1.30-1.10 (m, 14H); MS (ES+) m/z 486 (M+H)+.

Provenance & Evidence