Sodium Hydroxide → HCID 66932435, compound

Participants

Reaction Steps

(E)-3-{1′-(5-Fluoro-1H-indol-3-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester was obtained starting from (E)-3-{4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (135 mg, 0.45 mmol, Intermediate 1, free base) and 5-fluoro-1H-indole, according to the procedure described in Example 50, Step A (170 mg, 85%). The methyl ester was hydrolyzed with 4 M NaOH following the procedure described in Example 40, Step B, giving (E)-3-{1′-(5-fluoro-1H-indol-3-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid (100 mg, 63%). The resulting product was treated with NH2OTHP according to the procedure described in Example 40, Step C, giving (E)-3-{1′-(5-fluoro-1H-indol-3-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide. Finally, removal of the THP protecting group following the procedure described in Example 40, Step C gave (E)-3-{1′-(5-fluoro-1H-indol-3-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-hydroxy-acrylamide hydrochloride (76 mg) as a white solid.

Provenance & Evidence