Morpholine → 6-(Methyloxy)-2-[3-(4-morpholinyl)propanoyl]-7-nitro-1,2,3,4-tetrahydroisoquinoline

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Reaction Conditions

Reaction Steps

A solution of 2-acryloyl-6-(methyloxy)-7-nitro-1,2,3,4-tetrahydroisoquinoline (425 mg, 1.62 mmol) in methanol (5 mL) was treated with morpholine (1.00 mL, 11.5 mmol, Aldrich) and heated at 65° C. in a sealed tube for 16 h. The mixture was cooled, concentrated, and partitioned between ethyl acetate and saturated aqueous ammonium chloride. The organic layer was separated, dried over magnesium sulfate, filtered, and purified by chromatography on SiO2 (dichloromethane to 25% methanol/dichloromethane) to give 6-(methyloxy)-2-[3-(4-morpholinyl)propanoyl]-7-nitro-1,2,3,4-tetrahydroisoquinoline. This material was taken directly to the next step without a determination of yield. 1H NMR (400 MHz, DMSO-d6) is complicated by amide rotomers δ ppm 2.32-2.41 (m, 4 H), 2.52-2.62 (m, 4 H), 2.79-2.97 (two app triplets at 2.83 and 2.94, 2 H), 3.48-3.58 (m, 4 H), 3.63-3.72 (m, 2 H), 3.89 (s, 3 H), 4.55-4.69 (two singlets at 4.57 and 4.67, 2 H), 7.18-7.21 (m, 1 H), 7.80 (s, 1 H); ESIMS (M+H)+=350.

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