2-Quinolinecarboxaldehyde → HCID 66932339, compound

Participants

Reaction Steps

A suspension of (E)-3-{4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (169 mg, 0.500 mmol, Intermediate 1, hydrochloride salt) in 1 M Na2CO3, was stirred for 10 minutes, then extracted with DCM and treated with quinoline-2-carbaldehyde (96 mg, 0.61 mmol) and sodium triacethoxyborohydride (159 mg, 0.750 mmol) following the procedure described in Example 55, Step A, giving (E)-3-{1′-(quinolin-2-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (196 mg) as a yellow solid. The ester was hydrolyzed as described in Example 55, Step B, giving (E)-3-{1′-(quinolin-2-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid (190 mg) as an orange solid (hydrochloride salt). The acid was suspended in DCM (5 ml), TEA (0.16 ml, 1.16 mmol) was added, and the clear solution was treated with NH2OTHP following the procedure described in Example 1, Step B, giving (E)-3-{1′-(quinolin-2-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide (162 mg) as a yellow solid. The compound was then was dissolved in DCM (5 ml) and treated with 4 M HCl in dioxane (0.4 ml, 1.6 mmol) as described in Example 55, Step D, giving a yellow solid (145 mg, di-hydrochloride salt)

Provenance & Evidence