Reaction Steps
A mixture of (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((2-(but-3-en-1-yl)-4-fluorobenzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (50 mg, 0.079 mmol) and Grubb's II catalyst (66.7 mg, 0.079 mmol) in DCM (50 mL) was refluxed for 2 h. It was then concentrated and the residue was dissolved in MeOH (2 mL). NaBH4 (2.97 mg, 0.079 mmol) was added and the reaction mixture 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 to obtain an oil, which was then purified by biotage, eluting with 20% EtOAc/hexane to obtain ethyl (2S)-2-(tert-butoxy)-2-{16-fluoro-4,25-dimethyl-11,24-dioxa-1,5,7,8-tetraazapentacyclo[23.2.2.16,9.02,7.013,18]triaconta-2,4,6(30),8,13(18),14,16-heptaen-3-yl}acetate (36 mg, 0.059 mmol, 75% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.33-7.27 (m, 1H), 6.95 (dd, J=10.3, 2.7 Hz, 1H), 6.85 (td, J=8.3, 2.7 Hz, 1H), 6.56 (s, 1H), 6.07 (s, 1H), 4.78-4.64 (m, 4H), 4.58 (t, J=11.2 Hz, 1H), 4.18-4.11 (m, 2H), 3.90 (t, J=11.0 Hz, 1H), 3.44 (d, J=5.1 Hz, 2H), 3.05 (d, J=11.5 Hz, 1H), 2.95-2.85 (m, 1H), 2.83-2.72 (m, 2H), 2.63 (s, 3H), 2.03-1.88 (m, 2H), 1.84-1.62 (m, 8H), 1.31-1.24 (m, 15H). LCMS (M+1)=611.4.
