N,O-Dimethylhydroxylamine → 2-amino-5-bromo-N-methoxy-N-methylnicotinamide

To a solution of 2-amino-5-bromonicotinic acid (7 g, 32.3 mmol), N,O-dimethylhydroxylamine (5.99 g, 61.37 mmol) in N-methylmorpholine (60 ml) and dichloromethane (500 ml) at 0° C. was added PyBop (25.2 g, 48.45 mmol) portionwise. The solution was allowed to warm to room temperature and the mixture was stirred at room temperature for 18 hours. The reaction mixture was washed with a 2M aqueous solution of NaOH and with a 10 wt % solution of citric acid. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The resulting oil was dissolved in ether and the formed solid was filtered off. The mother liquors were concentrated in vacuo to approximatively half of the original volume. This solution was diluted with dichloromethane and stirred vigorously while adding a 2M HCl solution in diethylether until complete formation of the precipitate. The solid was filtered off and partitioned between a 2M aqueous solution of NaOH and EtOAc. The organic layer was collected, dried over sodium sulfate, filtered and concentrated to dryness to afford the title compound as a cream solid (5.26 g, 63% yield).

1. washThe reaction mixture was washed with a 2M aqueous solution of NaOH and with a 10 wt % solution of citric acid
2. dry with materialThe organic layer was dried over magnesium sulfate
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. dissolutionThe resulting oil was dissolved in ether
6. filtrationthe formed solid was filtered off
7. concentrationThe mother liquors were concentrated in vacuo to approximatively half of the original volume
8. additionThis solution was diluted with dichloromethane
9. stirringstirred vigorously
10. additionwhile adding a 2M HCl solution in diethylether until complete formation of the precipitate
11. filtrationThe solid was filtered off
12. custompartitioned between a 2M aqueous solution of NaOH and EtOAc
13. customThe organic layer was collected
14. dry with materialdried over sodium sulfate
15. filtrationfiltered
16. concentrationconcentrated to dryness

ORDレコード

ord-1680638a8cba4d60900f6c35f3f5033a

出典データセット

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08741931B2