反应详情

A catalytic amount of N,N-dimethylformamide (2 drops) was added to a stirred suspension of 5-bromo-2-(methylthio)pyrimidine4-carboxylic acid (2.07 g, 8.33 mmol) and a 2 M solution of oxalyl chloride (21 mL, 0.042 mol) in dichloromethane under nitrogen at r.t. Vigorous effervescence was observed. After 30 min everything had dissolved and the solvent was then evaporated in vacuo. The residue was dissolved in dichloromethane (20 mL) and placed under nitrogen. Triethylamine (2.32 mL, 16.66 mmol) was added to this stirred solution at r.t. followed by 4-aminopyridin-3-yl diethylcarbamodithioate (2.01 g, 8.33 mmol). Everything quickly dissolved with a noticeable exotherm. After 3 h at r.t. tlc showed a new major product. The reaction was diluted with dichloromethane (20 mL) and washed with a saturated aqueous solution of sodium hydrogen carbonate (40 mL). The organic layer was separated, dried over sodium sulfate, filtered and the solvent evaporated in vacuo. The residue was purified by flash chromatography (ethyl acetate/hexane 15:85 to 60:40) to yield 4-(5-bromo-2-(methylthio)pyrimidine-6-carboxamido)pyridin-3-yl diethylcarbamodithioate (1.99 g, 51%) as a pale yellow amorphous solid. 1H NMR: δ (CDCl3, 400 MHz) 1.30 (t, J=7 Hz, 3H), 1.51 (t, J=7 Hz, 3H), 2.60 (s, 3H), 3.93-4.08 (m, 4H), 8.57-8.62 (m, 2H), 8.69 (d, J=6 Hz, 1H), 8.85 (s, 1H), 10.67 (s, 1H).

1. customat r.t
2. dissolutionAfter 30 min everything had dissolved
3. customthe solvent was then evaporated in vacuo
4. dissolutionThe residue was dissolved in dichloromethane (20 mL)
5. dissolutionEverything quickly dissolved with a noticeable exotherm
6. washwashed with a saturated aqueous solution of sodium hydrogen carbonate (40 mL)
7. customThe organic layer was separated
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. customthe solvent evaporated in vacuo
11. customThe residue was purified by flash chromatography (ethyl acetate/hexane 15:85 to 60:40)