反应详情

To a mixture of (S,E)-6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-5-methyl-7-(4-methylpent-1-en-1-yl)pyrazolo[1,5-a]pyrimidine-2-carboxylic acid (30 mg, 0.072 mmol) and (4-fluoro-3-methylphenyl)methanamine (20.00 mg, 0.144 mmol) in DMF (1.5 mL) was added DIEA (0.063 mL, 0.359 mmol), HATU (54.6 mg, 0.144 mmol) and DMAP (1.756 mg, 0.014 mmol) and the resulting mixture was stirred at room temp for 16 h. At this point LCMS indicated completion of reaction. Water was then added and the mixture was extracted with ether (25 mL), washed with brine (15 mL), dried (Na2SO4), filtered and concentrated. Crude was then treated with 1N NaOH (0.216 mL, 0.216 mmol) in MeOH (1.500 mL) at 60° C. for 5 h. Mixture was then cooled and purified by prep-HPLC to afford (S,E)-2-(tert-butoxy)-2-(2-((4-fluoro-3-methylbenzyl)carbamoyl)-5-methyl-7-(4-methylpent-1-en-1-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetic acid (12.2 mg, 0.023 mmol, 31.6% yield). 1H NMR (500 MHz, DMSO-d6) δ 8.91 (t, J=6.4 Hz, 1H), 7.25 (d, J=7.3 Hz, 1.5H), 7.22-7.17 (m, 1.5H), 7.12-7.00 (m, 2H), 6.93 (s, 1H), 5.34 (br. s., 1H), 4.46 (t, J=5.6 Hz, 2H), 2.63 (s, 3H), 2.34 (t, J=6.3 Hz, 2H), 2.22 (s, 3H), 1.88-1.77 (m, 1H), 1.08 (s, 9H), 1.00 (dd, J=6.7, 2.4 Hz, 6H). LCMS (M+H)=511.33.

1. customcompletion of reaction
2. extractionthe mixture was extracted with ether (25 mL)
3. washwashed with brine (15 mL)
4. dry with materialdried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated
7. temperatureMixture was then cooled
8. custompurified by prep-HPLC