Lithium hydroxide, monohydrate → (S)-2-(7-(4-(Allyloxy)-4-methylpiperidin-1-yl)-2-(4'-fluoro-2'-((S)-pent-4-en-2-yloxy)-[1,1'-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of (S)-ethyl-2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(4′-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 (32 mg, 0.048 mmol, 1 equiv) in MeOH (1.0 mL) and water (0.1 mL) was added LiOH.H2O (60 mg, 1.43 mmol, 30 equiv). The reaction was heated to 60° C. for 2 h. Upon cooling to ambient temperature, the reaction was then filtered and purified via preparative HPLC with the following conditions: Column. XBridge Phenyl, 19×mm, 5-1 μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: 20-60% B over 20 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Product (7 mg, 23%) isolated. 1H NMR (600 MHz, DMSO-d6) δ 8.41 (s, 1H), 7.89 (d, J=7.7 Hz, 1H), 7.52 (t, J=7.7 Hz, 1H), 7.36-7.30 (m, 2H), 7.10 (d, J=11.6 Hz, 1H), 7.04 (s, 1H), 6.88-6.81 (m, 1H), 6.31 (d, J=6.1 Hz, 1H), 5.58 (s, 1H), 4.66-4.60 (m, 1H), 4.53 (q, J=7.0 Hz, 1H), 4.37 (t, J=12.1 Hz, 1H), 3.64-3.55 (m, 4H), 2.88 (br. s., 1H), 2.53 (s, 3H), 2.40-2.32 (m, 1H), 2.31-2.24 (m, 1H), 1.96-1.59 (m, 4H), 1.32 (s, 3H), 1.16 (s, 9H), 1.13 (d, J=6.1 Hz, 3H). LCMS (M+1)=643.5.

Provenance & Evidence