Reaction Steps
A mixture of (S)-ethyl 2-(2-(((2-allyl-4-methylbenzyl)oxy)methyl)-7-(4-(allyloxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (50 mg, 0.081 mmol) and Grubbs II catalyst (68.6 mg, 0.081 mmol) in DCM (50 mL) was refluxed for 2 h. It was then concentrated and the residue was dissolved in MeOH (2 mL). NaBH4 (3.06 mg, 0.081 mmol) was then added and the reaction was stirred at rt for 1 h. It was then diluted with water, extracted with EtOAc. The organic layer was dried over MgSO4, filtered and concentrated. The residue was purified by biotage, eluting with 20% EtOAc/hexane to isolate ethyl (2S)-2-(tert-butoxy)-2-{4,16,24-trimethyl-11,23-dioxa-1,5,7,8-tetraazapentacyclo[22.2.2.16,9.02,7.013,18]nonacosa-2,4,6(29),8,13(18),14,16-heptaen-3-yl}acetate (30 mg, 0.051 mmol, 62.6% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.36-7.25 (m, 1H), 7.08-6.97 (m, 2H), 6.50 (s, 1H), 6.16 (s, 1H), 4.88 (s, 2H), 4.76-4.59 (m, 3H), 4.24-4.08 (m, 2H), 3.96 (t, J=11.0 Hz, 1H), 3.57-3.40 (m, 2H), 2.92 (d, J=11.0 Hz, 1H), 2.80-2.72 (m, 2H), 2.69-2.59 (m, 4H), 2.34 (s, 3H), 2.11-2.01 (m, 1H), 1.98-1.86 (m, 3H), 1.86-1.74 (m, 2H), 1.76-1.60 (m, 2H), 1.29-1.22 (m, 12H), 1.19 (t, J=7.2 Hz, 3H). LCMS (M+1)=593.5.
