反应详情

温度

0 °C

Silver cyanate (0.15 g, 0.98 mmol) was added in one portion to a solution of iodine (0.091 g, 0.36 mmol) in THF (2 mL) at −15° C. and the mixture was stirred 1 hour before 7-(2-fluoropyridin-3-yl)-N3,N3-dimethyl-5′H-spiro[chromeno[2,3-c]pyridine-5,4′-oxazole]-2′,3-diamine as a stock solution in THF (2 mL) was added dropwise and the solution was stirred minutes at 0° C. for 2 h. The reaction was filtered through a pad of celite with THF and then 2 M ammonia in iPrOH (1 mL, 2.0 mmol) was added and the solution was stirred at RT for 12 h and then concentrated. The crude material was taken up in DCM and washed with aqueous sodium thiosulfate, saturated aqueous sodium bicarbonate, saturated aqueous NaCl, and dried over sodium sulfate. The solution was filtered and concentrated in vacuo to give the crude material. The crude material was purified by silica gel chromatography by eluting with 1:25 MeOH in DCM and then repurified by reverse-phase preparative HPLC using a Phenomenex Gemini column, 10 micron, C18, 100 Å, 150×30 mm, 0.1% TFA in CH3CN/H2O, gradient 5% to 100% over 15 min. The purified compound was partitioned between CHCl3 and 1N NaOH. The layers were separated and the aqueous layer was extracted with CHCl3. The combined organic extracts were washed with aqueous saturated sodium chloride and dried oversodium sulfate. The solution was filtered and concentrated in vacuo to give the above titled compound as the free base. MS m/z=392.2 [M+H].

1. additionwas added dropwise
2. filtrationThe reaction was filtered through a pad of celite with THF
3. stirringthe solution was stirred at RT for 12 h
4. concentrationconcentrated
5. washwashed with aqueous sodium thiosulfate, saturated aqueous sodium bicarbonate, saturated aqueous NaCl
6. dry with materialdried over sodium sulfate
7. filtrationThe solution was filtered
8. concentrationconcentrated in vacuo
9. customto give the crude material
10. customThe crude material was purified by silica gel chromatography
11. washby eluting with 1:25 MeOH in DCM
12. customrepurified by reverse-phase preparative HPLC
13. customover 15 min
14. customThe purified compound was partitioned between CHCl3 and 1N NaOH
15. customThe layers were separated
16. extractionthe aqueous layer was extracted with CHCl3
17. washThe combined organic extracts were washed with aqueous saturated sodium chloride
18. dry with materialdried oversodium sulfate
19. filtrationThe solution was filtered
20. concentrationconcentrated in vacuo