反应详情

A solution of sodium nitrite (275 mg, 3.98 mmol) in water (1.6 mL) was slowly added to a cooled mixture of (2R)-5-Amino-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (1.00 g, 3.98 mmol, Intermediate 1) in 10% H2SO4 (0.8 mL conc H2SO4+7.2 mL water) at 0° C. The ice bath was removed and the stirred reaction was allowed to warm to ambient temperature. The reaction was then placed into a 70° C. oil bath and heated to 100° C. Bubbling was observed and heating was continued until LCMS analysis showed a completed reaction. The reaction was slowly quenched/neutralized with concentrated aqueous NH4OH (about 2 mL) such that the pH was about 8 at the end of multiple sonication/heating cycles in order to produce a stable pH and a solid suitable for filtration. The solid was collected by filtration and washed with water. The solid was then air dried and chromatographed by first mixing with about twice the amount of silica and then dry loading on a silica gel column. The product was eluted with 10% MeOH/DCM. Pooling and concentration of the product containing fractions provided the title compound. MS: m/z=253 (M+1).

1. customThe ice bath was removed
2. customthe stirred reaction
3. customwas then placed into a 70° C.
4. temperatureheated to 100° C
5. customBubbling
6. temperatureheating
7. customa completed reaction
8. temperatureof multiple sonication/heating cycles in order
9. customto produce a stable pH
10. filtrationa solid suitable for filtration
11. filtrationThe solid was collected by filtration
12. washwashed with water
13. customair dried
14. customchromatographed
15. additionby first mixing with about twice the amount of silica
16. customdry loading on a silica gel column
17. washThe product was eluted with 10% MeOH/DCM
18. additionPooling and concentration of the product containing fractions