Sodium Hydroxide → 3,5-Diamino-6-chloro-pyrazine-2-carboxylic acid {(S)-2-[3-(4-methoxy-phenyl)-propylamino]-pentyl}-amide hydrochloride

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Reaction Steps

A solution of 3,5-Diamino-6-chloro-pyrazine-2-carboxylic acid ((S)-2-amino-pentyl)-amide hydrochloride (Example 4) (400 mg, 1.467 mmol), 3-(4-methoxyphenyl)propionaldehyde (181 mg, 1.103 mmol) and sodium triacetoxyborohydride (467 mg, 2.205 mmol) in DCM (150 mL) is heated at reflux overnight. The reaction mixture is allowed to cool, and 1 N NaOH solution (50 mL) and DCM (50 mL) are added. The organic phase is separated and the aqueous phase is extracted once with DCM. The combined organic phases are washed with sat. aq. NaCl solution, dried (MgSO4), and concentrated in vacuo to afford a yellow solid. Purification by flash column chromatography (SiO2, MeOH:DCM, gradient 2-10%+0.1% TEA) affords the title compound. [M+H]+ 421. 1H NMR (400 MHz, CDCl3) δ 8.69 (2H, br), 8.23 (1H, t), 7.25 (4H, br), 7.11 (2H, d), 6.84 (2H, d), 3.72 (3H, s), 3.55-3.45 (2H, m), 3.25-3.15 (1H, m), 3.03-2.92 (2H, m), 2.58 (2H, t), 1.85-1.73 (2H, m), 1.65-1.27 (4H, m), 0.89 (3H, t).

Provenance & Evidence