Dimethylformamide → HCID 68467899, compound

Participants

Reaction Steps

A solution (0.5 M) of 6-cyclohexyl-4H-thieno[3,2-b]pyrrole-2-carboxylic acid in DMF was treated with K2CO3 (2 eq.) and MeI (4 eq.). The reaction mixture was stirred at RT for 2 days. After dilution with AcOEt it was washed with water, brine and dried. Evaporation of the solvent gave a residue that was purified by flash chromatography on silica gel (1:4 AcOEt/petroleum ether) affording methyl 6-cyclohexyl-4-methyl-4H-thieno[3,2-b]pyrrole-2-carboxylate that was dissolved in DCE. POCl3 (1.4 eq.) was poured in a flask and cooled at 0° C. under nitrogen atmosphere. DMF (1.2 eq.) was added and the resulting oil was stirred at RT for 6 h, and then cooled again to 0° C. To this cool oil was added the previously prepared solution (0.02 M) in DCE. After stirring for 12 h, the reaction mixture was treated with aqueous Na2CO3 (30% solution) and extracted with AcOEt. The combined organic phase was washed with brine, dried. Evaporation of the solvent under reduced pressure gave a crude that was dissolved in dry MeOH. The resulting solution (0.1 M) was treated with K2CO3 (1 eq.) and TosMIC (1 eq.). The reaction mixture was heated to reflux for 12 h, then cooled and diluted with water. The aqueous phase was extracted with AcOEt. The combined organic phase was washed with water and brine and dried. After concentration under vacuum, the resulting crude was dissolved in MeOH. The resulting solution (0.1 M) was treated with aqueous NaOH (2 N solution, 4 eq.). The reaction mixture was heated to 80° C. for 1 h. After cooling down, the reaction was acidified at pH 2 with aqueous HCl (3 M) affording a precipitate that was filtered, dissolved in the minimum amount of DMSO and purified by RP-HPLC (Conditions: Waters X-TERRA MS C18, 5 micron, 19×150 mm; flow: 20 mL/min; Gradient: A: H2O+0.1% TFA; B: MeCN+0.1% TFA; linear from 95% A to 5% A in 10 min) to afford the title compound (3%) as a solid.

Provenance & Evidence