Sodium borohydride → Methyl (2S)-2-(tert-butoxy)-2-[(22S)-17-fluoro-4,22,28-trimethyl-21,27-dioxa-1,5,7,8-tetraazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetate

Participants

Reaction Steps

A solution of (S)-methyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(5′-fluoro-2′-((S)-pent-4-en-2-yloxy)-[1,1′-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.17 g, 0.25 mmol, 1 equiv) in DCE (50 mL) was heated to 80° C. The Hoyveda Grubbs 2nd generation catalyst (31 mg, 0.05 mmol, 0.2 equiv) was added. The pale green brown solution was stirred for 1.5 h and then allowed to cool to ambient temperature. The reaction was concentrated in vacuo. The dark residue was then taken up in MeOH (5 mL) and NaBH4 (13 mg, 0.35 mmol, 1.4 equiv) was added. After stirring 30 min, the reaction was diluted with EtOAc and washed with water. The EtOAc layer was dried (Na2SO4) and concentrated in vacuo. The crude product was purified by flash column chromatography (0-100% EtOAc in hexane) to provide the product as a colorless film (62 mg, 38%). 1H NMR (400 MHz, CDCl3) δ 8.59 (s, 1H), 7.80 (s, 1H), 7.51 (s, 1H), 7.39-7.31 (m, 1H), 7.09 (s, 1H), 7.05-6.87 (m, 3H), 5.93-5.82 (m, 1H), 4.68-4.42 (m, 2H), 4.27-4.17 (m, 1H), 3.84-3.68 (m, J=3.5 Hz, 4H), 3.56-3.22 (m, 2H), 3.03-2.85 (m, 1H), 2.62 (br. s., 3H), 2.02-1.70 (m, J=12.8 Hz, 10H), 1.26-1.21 (m, 12H), 1.15 (d, J=6.0 Hz, 3H). LCMS (M+1)=659.45.

Provenance & Evidence