Sodium Hydroxide → HCID 71259120, compound

Participants

Reaction Steps

To a mixture of (S)-6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(4,4-dimethylcyclohex-1-en-1-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylic acid (30 mg, 0.068 mmol) and (4-fluoro-3-methylphenyl)methanamine (18.83 mg, 0.135 mmol) in DMF (1.5 mL) was added DIEA (0.059 mL, 0.338 mmol), HATU (51.4 mg, 0.135 mmol) and DMAP (1.653 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 (0.203 mL, 0.203 mmol) in MeOH (1.500 mL) at 60° C. for 5 h. Mixture was then cooled and purified by prep-HPLC to afford (S)-2-(tert-butoxy)-2-(7-(4,4-dimethylcyclohex-1-en-1-yl)-2-((4-fluoro-3-methylbenzyl)carbamoyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetic acid (16.5 mg, 0.029 mmol, 43.2% yield). 1H NMR (500 MHz, DMSO-d6) δ 8.58 (t, J=6.0 Hz, 1H), 7.25 (d, J=7.6 Hz, 1H), 7.19 (dd, J=8.2, 5.2 Hz, 1H), 7.12-7.06 (m, 1H), 6.92 (s, 1H), 6.33 (br. s., 0.7H), 5.85 (br. s.; 0.3H), 5.31 (br. s., 0.7H), 5.23 (br. s., 0.3H), 4.54-4.39 (m, 2H), 2.67 (br. s., 1H), 2.59 (s, 2H), 2.23 (d, J=1.5 Hz, 3H), 2.14-2.10 (m, 4H), 1.70-1.59 (m, 2H), 1.18 (br. s., 3H), 1.14 (s, 7H), 1.08 (br. s., 2H), 1.07 (br. s., 4H). LCMS (M+H)=537.5.

Provenance & Evidence