Formaldehyde → 2-[(1-Methylethyl)oxy]-5-[3-(2-methyl-1,2,3,4-tetrahydro-5-isoquinolinyl)-1,2,4-oxadiazol-5-yl]benzonitrile

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Reaction Steps

To a solution of 2-[(1-methylethyl)oxy]-5-[3-(1,2,3,4-tetrahydro-5-isoquinolinyl)-1,2,4-oxadiazol-5-yl]benzonitrile (Example 3, 25.0 mg, 0.069 mmol) and formaldehyde (37% w/v in H2O, 8.0 μL, 0.10 mmol) in DCM (5 mL) was added NaBH(OAc)3 (29 mg, 0.14 mmol) and the resulting solution stirred at room temperature for 20 min. Brine (5 mL) was added, and the aqueous extracted with DCM (5 mL). The combined organics were concentrated in vacuo to give a white solid. This solid was redissolved in DMSO-MeOH, added to an SCX cartridge and washed with MeOH. The product was eluted with NH3 in MeOH; concentration in vacuo gave a white solid (20.1 mg, 78%). 1H NMR (400 MHz, CDCl3) δ 8.41 (1H, d), 8.32 (1H, dd), 7.98 (1H, d), 7.29 (1H, t), 7.20 (1H, d), 7.12 (1H, d), 4.79 (1H, sept), 3.67 (2H, s), 3.30 (2H, t), 2.75 (2H, t), 2.49 (3H, s), 1.47 (6H, d).

Provenance & Evidence