Hydrochloric Acid → 13-Cyclohexyl-6-methyl-5,6,7,8-tetrahydrothieno[2',3':4,5]pyrrolo[2,1-a][2,5] benzodiazocine-11-carboxylic acid

Participants

Reaction Steps

A solution of tert-butyl 6-cyclohexyl-5-(2-formylphenyl)-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate (1 eq., prepared as described in Example 1, Step 4) in dry methanol (0.05 M) was treated with methylamine (1.5 eq., 2 M solution in THF) at RT for 1 h. Sodium borohydride (2 eq.) was then added and the mixture stirred overnight at RT. The residue was diluted with EtOAc and washed with a saturated NaHCO3 solution and with brine, then dried over sodium sulfate and evaporated in vacuo. The foregoing compound (1 eq.) was dissolved in dry THF (0.14M) was treated with borane-dimethylsulfide complex (20 eq., 2M solution in THF) overnight at RT. The reaction mixture was then treated with HCl in methanol (40 eq., 1.25 M solution) and heated to reflux for 1 h. The volatiles were evaporated in vacuo and the residue purified by RP-HPLC (column: Waters XTERRA PREP MS C18, 10 μm; solvents: A: water+0.1% trifluoroacetic acid; B: MeCN+0.1% trifluoroacetic acid; 25% B in A isocratic for 3 min, linear to 20% A in B in 12 min) to afford the title compound after lyophilisation as a colourless powder (39%). 1H-NMR (400 MHz, DMSO-d6, 300 K, δ) 12.83 (bs, 1H), 9.86 (bs, 1H), 8.05 (s, 1H), 7.94-7.90 (m, 1H), 7.65-7.60 (m, 2H), 7.48-7.45 (m, 1H), 4.66 (d, J 15.3, 1H), 4.39 (d, J 12.7, 1H), 3.70-3.20 (m, 4H, partially hidden by H2O signal), 3.06 (s, 3H), 2.50 (m, 1H, hidden by DMSO signal), 2.03-1.36 (m, 10H). MS (ES+) m/z: 395 [M+H]+.

Provenance & Evidence