反应详情

To a dry 16×100 mm CHEMGLASS® reaction tube under N2 was added 2-fluoro-4-iodonicotinaldehyde (600 mg, 2.390 mmol), (4-fluorophenyl)hydrazine (332 mg, 2.63 mmol), and anhydrous NMP (3.2 mL). The reaction mixture was flushed with argon, securely capped, stirred for 20 min at room temperature, and then placed in a 185° C. oil bath for 2 h. The reaction mixture was then allowed to stir at room temperature for 16 h. The reaction mixture was diluted with EtOAc (200 mL) and the organic layer was extracted with water (5×50 mL), brine (1×50 mL), dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by BIOTAGE® Silica gel chromatography on a 90 g Thompson Single Step silica cartridge using a linear gradient from 100% hexanes to 100% dichloromethane over 12 column volumes to give 480 mg (59.2%) of the title compound, Intermediate 1A, as an off white solid. 1H NMR (500 MHz, CD3OD) δ ppm 8.22-8.28 (3 H, m), 8.15 (1 H, s), 7.78 (1 H, d, J=4.88 Hz), 7.25-7.37 (2 H, m). LC/MS (Condition A): 100% purity; ret. T=2.9 min, (M+H)+ 339.97.

1. customTo a dry
2. custom16×100 mm CHEMGLASS® reaction tube under N2
3. customThe reaction mixture was flushed with argon
4. customsecurely capped
5. customplaced in a 185° C.
6. customfor 2 h
7. stirringto stir at room temperature for 16 h
8. additionThe reaction mixture was diluted with EtOAc (200 mL)
9. extractionthe organic layer was extracted with water (5×50 mL), brine (1×50 mL)
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. customevaporated to dryness
13. customThe residue was purified by BIOTAGE® Silica gel chromatography on a 90 g Thompson Single Step silica cartridge