反应详情

To a solution of 3′,4′,5′,6′-tetrahydro-2′H-[2,4′]bipyridinyl-6,1′-dicarboxylic acid 1′-tert-butyl ester (150 mg, 0.49 mmol), methyl-(R)-1,2,3,4-tetrahydro-naphthalen-1-yl-amine (0.079 g, 0.49 mmol), and diisopropylethylamine (0.50 mL, 0.49 mmol) in DMF (10 mL) was added dropwise BOP (238 mg, 0.49 mmol) at RT. After stirring overnight at RT, the reaction mixture was poured on water (10 mL) and extracted with ethylacetate (20 mL). The aqueous phase was re-extracted with ethylacetate (20 mL). The combined organic layers were washed with aq. sat. sodium bicarbonate solution (30 mL), 1M HCl solution (30 mL) and brine (30 mL), dried over sodium sulfate, filtered, and evaporated under reduce pressure. The crude mixture was purified by column chromatography on silica gel (ethylacetate/hexane 4:1) to give 6-[methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-carbamoyl]-3′,4′,5′,6′-tetrahydro-2′H-[2,4′]bipyridinyl-1′-carboxylic acid tert-butyl ester (215 mg, 97%). 1H-NMR (400 MHz, CDCl3): δ=1.47 (s, 9H), 1.64-2.05 (m, 8H), 2.18-2.22 (m, 1H), 2.72-2.81 (m, 4H), 2.82 (s, 3H), 4.15-4.25 (m, 2H), 5.15-5.20 (m, 1H), 7.18-7.25 (m, 5H), 7.53-7.71 (m, 1H), 7.73-7.74 (m, 1H).

1. additionthe reaction mixture was poured on water (10 mL)
2. extractionextracted with ethylacetate (20 mL)
3. extractionThe aqueous phase was re-extracted with ethylacetate (20 mL)
4. washThe combined organic layers were washed with aq. sat. sodium bicarbonate solution (30 mL), 1M HCl solution (30 mL) and brine (30 mL)
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. customevaporated
8. customThe crude mixture was purified by column chromatography on silica gel (ethylacetate/hexane 4:1)