(2S)-2-[5-ethoxy-2-fluoro-3-(1-methylpiperidin-4-yl)oxyphenyl]-2-[4-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]anilino]acetic acid → (S)-(4-carbamimidoyl-phenylamino)-[5-ethoxy-2-fluoro-3-(1-methyl-piperidin-4-yloxy)-phenyl]-acetic acid

Participants

Reaction Conditions

Reaction Steps

A solution of 5.1 g (S)-[4-(tert-butoxycarbonylamino-imino-methyl)-phenylamino]-[5-ethoxy-2-fluoro-3-(1-methyl-piperidin-4-yloxy)-phenyl]-acetic acid in 102 ml water/formic acid 1:1 was heated to 40° C. for 2.5 hrs. The solvents were evaporated in vacuo, the residue dissolved in water and the solution evaporated again (repeated twice). The residue was dissolved in methanol and 7N methanolic ammonia was added until pH=9, wereby a precipitate was formed. The mixture was cooled to 0° C., the solid isolated by suction filtration and dried. Afterwards it was suspended in water and the pH adjusted to 9 wiTh conc. ammonia. Suction filtration and drying gave 3 g (S)-(4-carbamimidoyl-phenylamino)-[5-ethoxy-2-fluoro-3-(1-methyl-piperidin-4-yloxy)-phenyl]-acetic acid. White solid. Mp.: 269° C. MS: 445 ([M+H]+).

Provenance & Evidence