反应详情

Mixture of methyl 2-(7-hydroxy-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetate (8.4 g, 23.90 mmol) and phosphoryl trichloride (10.94 ml, 120 mmol) was heated at reflux for 4 h. Then, cooled, concentrated and the dark residue taken up in EtOAc (500 mL) and stirred with ice-water for 30 min. Aqueous layer separated and organic layer washed with water (2×50 mL). The combine aq layers extracted with EtOAc (2×100 mL) and the combined organic layers washed with brine (100 mL), dried (Na2SO4/C), filtered and concentrated to give dark paste. Purification by flash column chromatography on silica gel column using 5-20% EtOAc/Hex afforded methyl 2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetate (5.6 g, 15.14 mmol, 63.3% yield) as off-white solid. 1H NMR (500 MHz, CDCl3) δ 7.76-7.71 (m, 2H), 7.18 (d, J=7.6 Hz, 1H), 6.92 (s, 1H), 3.93 (s, 2H), 3.78 (s, 3H), 2.89-2.84 (m, 4H), 2.63 (s, 3H), 1.86 (dt, J=6.5, 3.3 Hz, 4H). LCMS (M+H)=370.11.

1. temperaturewas heated
2. temperatureat reflux for 4 h
3. temperatureThen, cooled
4. concentrationconcentrated
5. customAqueous layer separated
6. washorganic layer washed with water (2×50 mL)
7. extractionThe combine aq layers extracted with EtOAc (2×100 mL)
8. washthe combined organic layers washed with brine (100 mL)
9. dry with materialdried (Na2SO4/C)
10. filtrationfiltered
11. concentrationconcentrated
12. customto give dark paste
13. customPurification by flash column chromatography on silica gel column