反应详情

温度

0 °C

Method b): To a solution of 5-cyanopicolinic acid (69.1 mg, 466 μmol, Eq: 1.1) in Methanol (6 ml) at 0° C. was added 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride hydrate (187 mg, 636 μmol, Eq: 1.5) and the mixture was stirred at 0° C. for 15 minutes. Added (R)-5-(5-amino-2-fluoro-phenyl)-5-methyl-1,1-dioxo-1,2,5,6-tetrahydro-1λ6-[1,4]thiazin-3-ylamine (115 mg, 424 μmol, Eq: 1.00) in Methanol (6 ml) and stirred at 23° C. overnight. Poured into sat NaHCO3-sol., extracted with ethyl acetate, the organic layer was dried over Na2SO4. Removal of the solvent in vacuum left a brown oil. The crude material was purified by silica gel flash chromatography (10 g): washed first with ethyl acetate, then added 5% of a 7 M solution of ammonia in methanol to give the 5-cyano-pyridine-2-carboxylic acid [3-((R)-5-amino-3-methyl-1,1-dioxo-1,2,3,6-tetrahydro-1λ6-[1,4]thiazin-3-yl)-4-fluoro-phenyl]-amide (63 mg, 157 μmol, 37.0% yield) as a light yellow solid. MS (ISP): m/z=402.4 [(M+H)+].

1. additionPoured
2. extraction, extracted with ethyl acetate
3. dry with materialthe organic layer was dried over Na2SO4
4. customRemoval of the solvent in vacuum
5. waitleft a brown oil
6. customThe crude material was purified by silica gel flash chromatography (10 g)
7. washwashed first with ethyl acetate
8. additionadded 5% of a 7 M solution of ammonia in methanol