Methanamine, N-methoxy-, hydrochloride (1:1) → 1-(2-Fluoro-4-iodophenyl)-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide

To a solution of N,O-dimethylhydroxylamine hydrochloride (8.78 g, 90 mmol) and iPr2NEt (15.7 mL, 90 mmol) in CH2Cl2 (100 mL) was added AlMe3 (1.8 M solution in toluene, 50 mL, 90 mmol) slowly at 0° C. under Ar atmosphere. After stirring for 1 h, a solution of methyl 1-(2-fluoro-4-iodophenyl)-5-methoxy-4-oxo-1,4-dihydropyridazine-3-carboxylate (12.1 g, 30 mmol) in CH2Cl2 (100 mL) was added slowly, and the mixture was stirred for 1 h at 0° C. The reaction mixture was poured into ice-water and the organic layer was separated. The aqueous layer was extracted with AcOEt. The combined organic layers were washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography eluting with AcOEt to give the title compound (9.96 g, 77% yield) as a white amorphous solid: 1H NMR (300 MHz, CDCl3): δ ppm 3.39 (3H, s), 3.70 (3H, s), 3.90 (3H, s), 7.39 (1H, t, J=8.1 Hz), 7.63-7.67 (2H, m), 7.77 (1H, d, J=2.3 Hz).

1. stirringthe mixture was stirred for 1 h at 0° C
2. customthe organic layer was separated
3. extractionThe aqueous layer was extracted with AcOEt
4. washThe combined organic layers were washed with brine
5. dry with materialdried over MgSO4
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by basic silica gel column chromatography
8. washeluting with AcOEt

ORD record

ord-7d899faac2a345bc9d5a8964b73df42b

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08778944B2