反应详情

To a solution of 6-methoxy-8-(4-methyl-[1,4]diazepan-1-yl)-4-oxo-1,4-dihydro-quinoline-2-carboxylic acid (2.10 mmol) (Reference Example 25b) and diisopropylethyl amine (1.4 mL, 8.6 mmol) in 34 mL dimethylformamide was added TBTU (1.40 g, 4.36 mmol) and HOBt (0.588 g, 4.35 mmol) followed by the addition of 4-morpholinoaniline (0.463 g, 2.60 mmol). The resulting dark brown solution was stirred at room temperature under nitrogen for 19 hours. The reaction was concentrated in vacuo and the resulting crude product was taken up in methylene chloride/methanol. Filtration of the resulting mixture afforded some product as a yellow solid. The filtrates were concentrated and partitioned between methylene chloride and saturated aqueous sodium bicarbonate. The organic layer was washed with saturated sodium bicarbonate, dried (MgSO4), and concentrated under vacuum to afford a brown solid. This was suspended in methanol and filtered to afford the desired product as a yellow solid (0.714 g, 69%). 1H NMR (300 MHz, DMSO, d6) δ 9.97 (bs, 1H, NH), 7.67 (d, 2H, Jo=8.8 Hz, ArH2′ & H6′), 7.47 (bs, 1H, ArH5), 7.00 (s, 1H, C═CH), 6.99 (d, 2H, Jo=8.8 Hz, ArH3′ & H5′), 6.71 (bs, 1H, ArH7), 3.85 (s, 3H, OCH3), 3.75 (t, 4H, J=4.6 Hz, OCH2CH2N), 3.70 (bs, 2H, ArNCH2CH2CH2NCH3), 3.55 (bs, 2H, ArNCH2CH2NCH3), 3.09 (t, 4H, J=4.6 Hz, OCH2CH2N), 2.95 (bs, 2H, ArNCH2CH2NCH3), 2.73 (bs, 2H, ArNCH2CH2CH2NCH3), 2.36 (s, 3H, NCH3), 2.07 (bs, 2H, ArNCH2CH2CH2NCH3); Mass Spec.: calc. for [C27H33N5O4+H]+ Theor. m/z=492; Obs. 492.

1. concentrationThe reaction was concentrated in vacuo
2. filtrationFiltration of the resulting mixture
3. customafforded some product as a yellow solid
4. concentrationThe filtrates were concentrated
5. custompartitioned between methylene chloride and saturated aqueous sodium bicarbonate
6. washThe organic layer was washed with saturated sodium bicarbonate
7. dry with materialdried (MgSO4)
8. concentrationconcentrated under vacuum
9. customto afford a brown solid
10. filtrationfiltered