Reaction Steps
A solution of (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(azidomethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.072 g, 0.144 mmol) and Ph3P (0.057 g, 0.216 mmol) in 1:9 (H2O/THF, 5 mL) was stirred at 55° C. for h. Then, cooled in ice-water bath and added DIEA (0.076 ml, 0.432 mmol) followed by freshly prepared acid chloride (To a solution of 2-(2-(allyloxy)phenyl)acetic acid (0.055 g, 0.288 mmol) in CH2Cl2 (5 mL) containing cat amount of DMF was added 2M oxalyl chloride (0.288 ml, 0.576 mmol) at rt. After 1 h, the reaction was concentrated and the residue was dissolved in CH2Cl2 (5 mL) and added to the amine). After the reaction mixture was taken up in Et2O (50 mL), washed with water (2×10 mL), brine (10 mL), dried (MgSO4), filtered, concentrated and the resulting yellow residue purified by prep-HPLC to afford (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((2-(2-(allyloxy)phenyl)acetamido)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.0559 g, 0.086 mmol, 59.9% yield) as off-white solid. 1H NMR (500 MHz, CDCl3) δ 7.28-7.30 (m, 1H), 7.23-7.27 (m, 1H), 6.96 (dt, J=1.0, 7.5 Hz, 1H), 6.89 (d, J=8.2 Hz, 1H), 6.29 (s, 1H), 6.25 (t, J=5.0 Hz, 1H), 5.92-6.06 (m, 2H), 5.88 (br. s., 1H), 5.44 (d, J=17.0 Hz, 1H), 5.33 (qd, J=1.6, 17.3 Hz, 1H), 5.17-5.21 (m, 2H), 4.60 (dd, J=3.8, 5.4 Hz, 2H), 4.56 (td, J=1.6, 5.2 Hz, 2H), 4.13-4.26 (m, 2H), 4.00 (d, J=4.9 Hz, 2H), 3.68 (s, 2H), 2.59 (s, 3H), 1.82-2.01 (m, 3H), 1.64-1.72 (m, 1H), 1.34 (s, 3H), 1.21-1.25 (m, 12H). LCMS (M+H)=648.7.
