反应详情

To a solution of 2,3-Di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazine (Intermediate E) (10 g, 31.7 mmol) in DCE (300 ml) was added DIPEA (6.09 ml, 34.9 mmol) followed by ethyl 7-oxoheptanoate (10.92 g, 63.4 mmol). The mixture was stirred at RT for 10 minutes and sodium triacetoxyborohydride (16.80 g, 79 mmol) was added portionwise. The reaction mixture was heated at 40° C. overnight and then added slowly to water (500 ml) and stirred at RT for 10 minutes. The organic layer was separated and the aqueous layer extracted with dichloromethane (2×200 ml). The combined organics were washed with brine (200 ml), dried over anhydrous sodium sulfate and concentrated in vacuo to give a pale yellow oil. Isolute Separtis SCX-2 (capture/release super cation exchange resin) (222 g, 127 mmol) was added to a column and the product was loaded with MeOH (50 ml). The column was flushed with MeOH (750 L) followed by 2 N NH3/MeOH (1000 ml, prepared from 280 ml 7 N+720 ml MeOH) to afford the title compound. No further purification was carried out; HPLC (Agilent 1200) Rt 6.38 min, Method B

1. temperatureThe reaction mixture was heated at 40° C. overnight
2. stirringstirred at RT for 10 minutes
3. customThe organic layer was separated
4. extractionthe aqueous layer extracted with dichloromethane (2×200 ml)
5. washThe combined organics were washed with brine (200 ml)
6. dry with materialdried over anhydrous sodium sulfate
7. concentrationconcentrated in vacuo
8. customto give a pale yellow oil
9. additionIsolute Separtis SCX-2 (capture/release super cation exchange resin) (222 g, 127 mmol) was added to a column
10. customThe column was flushed with MeOH (750 L)