4-Hydroxy-cyclopent-2-ene-1,2-dicarboxylic acid 2-methyl ester → 5-(1-tert-Butoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-3-hydroxy-cyclopent-1-enecarboxylic acid methyl ester

Participants

Reaction Steps

Reaction of compound the acid 23c (50 mg, 37 mmol) with (1R,2S)-1-amino-2-vinyl-cyclopropane carboxylic acid tert-butyl ester according to the method described in Example 1 step j, provided the title compound as a slightly yellow oil (50 mg, 38%). 1H-NMR (300 MHz, CDCl3): δ [(1.38 & 1.42) s, 9H], 1.75-1.83 (m, 1H), 2.00-2.21 (m, 3H), 3.55-3.63 (m, 1H), [(3.77 & 3.82) s, 3H], 4.20-4.38 (m, 1H), 4.65-4.80 (m, 1H), 5.13-5.20 (m, 1H), 5.22-5.38 (m, 1H), 5.60-5.82 (m, 1H), 6.95-6.96 (m, 2H). Inhibitors of the invention are achieved from the title compound by coupling of the afforded cyclopentenol derivative to a desired pyrimidinol for example as described in Example 3 step f, followed by hydrolysis of the methyl ester using a reagent like LiOH; coupling of a desired alkenylamine and macrocyclisation as described in Example 3 step h and i; hydrolysis of the tert. butyl ester by treatment with for example TFA and finally coupling of a desired sulphone amide derivative for example as described in Example 3, step k.

Provenance & Evidence