反应详情

温度

50 °C

45A (380 mg, 1.45 mmol) dissolved in 5 mL of anhydrous DMSO was added to a suspension containing (CH3)3S(I)O (3188 mg, 14.48 mmol) prereacted with NaH (579 mg, 14.48 mmol) in 15 mL of anhydrous DMSO. The reaction mixture was heated at 50° C. in an oil bath overnight. The reaction mixture was concentrated under high vaccuum to remove as much DMSO as possible, the resulting crude material was then dissolved in EtOAc and washed with a small amount of H2O. The aq. phase was extracted with EtOAc (2×50 ml). The organic phases were combined dried over MgSO4 then filtered on a thin pad of silica gel (1 cm). The silica gel was washed with more EtOAc and the resulting solution was concentrated under reduced pressure then purified on a 40 g silica column on the Companion machine using 0 to 20% MeOH in EtOAc gradient (with two 10 plateau at 10% MeOH then at 20% MeOH). The desired fractions were combined and concentrated under reduced pressure. These fractions were found to still contain some starting material. These samples were combined and repurified on preparative reverse phase chromatography (LCMS) using the long high pH 35-55% gradient on the XBridge Prep C18 OBD, 30×150, 5 um column. The pure fractions were combined and concentrated under reduced pressure. The resulting residue was placed under high vaccuum overnight. The yellow liquid was dissolved in 1 ml of distilled H2O and 300 μL of HCl 2N was added to the solution which was then filtered and freeze dried to yield 46.4 mg 45B (9% yield) as a yellow solid HCl salt. 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.46-1.60 (m, 1H) 2.28-2.48 (m, 2H) 2.99-3.30 (m, 4H) 3.52-3.64 (m, 3H) 4.04 (s, 3H) 4.54-4.78 (m, 2H) 8.01 (s, 1H) 8.03 (s, 1H). ES[M+H]+=277.2, HRMS[M+H]+ calc. for C15H24N4O+H=277.20229, [M+H]+ obs.=277.20211.

1. additionwas added to a suspension
2. concentrationThe reaction mixture was concentrated under high vaccuum
3. customto remove as much DMSO as possible, the resulting crude material
4. dissolutionwas then dissolved in EtOAc
5. washwashed with a small amount of H2O
6. extractionThe aq. phase was extracted with EtOAc (2×50 ml)
7. dry with materialThe organic phases were combined dried over MgSO4
8. filtrationthen filtered on a thin pad of silica gel (1 cm)
9. washThe silica gel was washed with more EtOAc
10. concentrationthe resulting solution was concentrated under reduced pressure
11. customthen purified on a 40 g silica column on the Companion machine
12. concentrationconcentrated under reduced pressure
13. customrepurified on preparative reverse phase chromatography (LCMS)
14. concentrationconcentrated under reduced pressure
15. dissolutionThe yellow liquid was dissolved in 1 ml of distilled H2O
16. addition300 μL of HCl 2N was added to the solution which
17. filtrationwas then filtered
18. customfreeze dried