Reaction Steps
A mixture of (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((2-(but-3-en-1-yl)-4-fluorobenzyl)(cyclopropyl)amino)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (45 mg, 0.067 mmol) and Grubb's II catalyst (5.65 mg, 6.66 μmol) in DCM (45 mL) was refluxed for 2 h. It was then concentrated and the residue was dissolved in MeOH (2 mL). NaBH4 (2.52 mg, 0.067 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. It was then purified by biotage, eluting with 25% EtOac/hexane to obtain ethyl (2S)-2-(tert-butoxy)-2-{11-cyclopropyl-16-fluoro-4,25-dimethyl-24-oxa-1,5,7,8,11-pentaazapentacyclo[23.2.2.16,9.02,7.013,18]triaconta-2,4,6(30),8,13(18),14,16-heptaen-3-yl}acetate (35 mg, 0.054 mmol, 81% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.14 (dd, J=8.4, 6.1 Hz, 1H), 6.90 (dd, J=10.3, 2.8 Hz, 1H), 6.77 (td, J=8.4, 2.8 Hz, 1H), 6.48 (s, 1H), 6.10 (s, 1H), 4.58-4.48 (m, 1H), 4.28-4.21 (m, 1H), 4.18-4.12 (m, 1H), 4.04 (d, J=1.0 Hz, 2H), 3.96-3.83 (m, 2H), 3.62 (d, J=13.8 Hz, 1H), 3.44-3.33 (m, 2H), 3.06-2.98 (m, 1H), 2.90-2.72 (m, 3H), 2.68-2.60 (m, 3H), 2.03-1.85 (m, 3H), 1.79-1.62 (m, 8H), 1.30-1.21 (m, 19H). LCMS (M+1)=650.3.
