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

HRID 401491

Reaction equation

HRID 401491 reaction equation
[NH2:1][C:2]1[N:10]=[CH:9][C:8]([Br:11])=[CH:7][C:3]=1[C:4](O)=[O:5].[CH3:12][NH:13][O:14][CH3:15].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN1CCOCC1.ClCCl>[NH2:1][C:2]1[N:10]=[CH:9][C:8]([Br:11])=[CH:7][C:3]=1[C:4]([N:13]([O:14][CH3:15])[CH3:12])=[O:5]

Participants

6

Reactant 3

HCID 14232N,O-DimethylhydroxylamineHCID 7374452-Amino-5-bromonicotinic acidHCID 2724699PyBOP

Product 1

HCID 596997242-amino-5-bromo-N-methoxy-N-methylnicotinamideYield 63%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 79724-MethylmorpholineSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-1680638a8cba4d60900f6c35f3f5033a
Source dataset
uspto-grants-2014_06
Patent number
US08741931B2

Linked notes

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