Ammonium Chloride → (RS)-3,5-difluoro-pyridine-2-carboxylic acid [3-(3-methyl-5-oxo-morpholin-3-yl)-phenyl]-amide

Participants

Reaction Conditions

Reaction Steps

A dried pressure tube was charged under an argon atmosphere with a dispersion of (RS)-3,5-difluoro-pyridine-2-carboxylic acid [3-(5-ethoxy-3-methyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-phenyl]-amide (0.348 g, 0.9 mmol) and ammonium chloride (0.182 g, 3.4 mmol) in methanol (10 ml). The sealed pressure tube was heated at 100° C. for 16 hours. After cooling, the reaction mixture was evaporated to dryness and directly purified by chromatography on an Isolute flash NH2 column using a gradient of dichloromethane/methanol=100/0 to 95/5 as the eluent. There were obtained 0.076 g (38% of theory) of (RS)-3,5-difluoro-pyridine-2-carboxylic acid [3-(3-methyl-5-oxo-morpholin-3-yl)-phenyl]-amide (=3,5-difluoro-pyridine-2-carboxylic acid [3-((RS)-3-methyl-5-oxo-morpholin-3-yl)-phenyl]-amide) as a white solid; mass (calculated) C17H15F2N3O3 [347.324]; (found) [M+H]+=348, and 0.113 g (57% of theory) of (RS)-3,5-difluoro-pyridine-2-carboxylic acid [3-(5-amino-3-methyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-phenyl]-amide (1) as a light yellow foam; mass (calculated) C17H16F2N4O2 [346.340]; (found) [M+H]+=347.

Provenance & Evidence