Methanamine, N-methoxy-, hydrochloride (1:1) → N,4-dimethoxy-N-methyl-6-oxo-[3-(trifluoromethyl)phenyl]-1,6-dihydropyridazine-3-carboxamide

To a solution of N,O-dimethylhydroxylamine hydrochloride (1.58 g, 16.2 mmol) and iPr2NEt (2.82 mL, 16.2 mmol) in CH2Cl2 (13 mL) was added AlMe3 (1.8 M solution in toluene, 9.0 mL, 16.2 mmol) dropwise at 0° C. under Ar atmosphere. After stirring for 1 h, a solution of methyl 4-methoxy-6-oxo-1-[3-(trifluoromethyl)phenyl]-1,6-dihydropyridazine-3-carboxylate (1.77 g, 5.4 mmol) in CH2Cl2 (15 mL) was added dropwise, and the mixture was stirred for 1 h at 0° C. The reaction mixture was poured into ice-water and extracted with AcOEt. The extract was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with AcOEt and crystallized from hexane/AcOEt to give the title compound (1.48 g, 83% yield) as a white solid: mp 127-129° C.; 1H NMR (300 MHz, CDCl3): δ ppm 3.37 (3H, s), 3.64 (3H, s), 3.91 (3H, s), 6.30 (1H, s), 7.55-7.60 (1H, m), 7.62-7.65 (1H, m), 7.82-7.86 (1H, m), 7.88 (1H, s). Anal. Calcd for C15H14F3N3O4: C, 50.42; H, 3.95; N, 11.76. Found: C, 50.47; H, 3.99; N, 11.83.

1. stirringthe mixture was stirred for 1 h at 0° C
2. extractionextracted with AcOEt
3. washThe extract was washed with brine
4. dry with materialdried over MgSO4
5. concentrationconcentrated under reduced pressure
6. customThe residue was purified by silica gel column chromatography
7. washeluting with AcOEt
8. customcrystallized from hexane/AcOEt

ORD record

ord-129fc975ae6d4877baeaddd2d55113c7

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08916566B2