Cesium carbonate → HCID 86762155, compound

Participants

Reaction Conditions

Reaction Steps

(±)-tert-butyl (4aR,7aR)-7a-(5-bromo-2,4-difluorophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-ylcarbamate was made from 5-bromo-2,4-difluorobenzaldehyde in the same fashion as (±)-tert-butyl (4aS,7aS)-7a-(2-fluoro-5-nitrophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-ylcarbamate from 2-fluoro-5-nitrobenzaldehyde (Step A to Step F, Preparation 1). A mixture of (±)-tert-butyl (4aS,7aS)-7a-(5-bromo-2,4-difluorophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-ylcarbamate (60 mg), 5-(prop-1-ynyl)pyridin-3-ylboronic acid (Preparation 9, 86 mg), cesium carbonate (174 mg), and PdCl2(PPh3)2 (19 mg) in DME (0.44 mL), EtOH (0.22 mL) and water (0.22 mL) was heated at 100° C. for 10 min in a microwave, and the crude reaction mixture was subjected to preparative HPLC eluting with 0-100% B (A: 95% H2O/5% MeCN, 10 mM NH4OAc; B: 5% H2O/95% MeCN, 10 mM NH4OAC over 12 min period to give the title compound as a white foam (22 mg). 1H NMR (400 MHz, CHLOROFORM-d) δ 8.65 (br. s., 1H), 7.82 (s, 1H), 7.65 (t, J=8.7 Hz, 1H), 7.00 (t, J=10.3 Hz, 1H), 4.23-4.13 (m, 1H), 4.12-4.04 (m, 1H), 3.30 (d, J=11.5 Hz, 1H), 3.00-2.83 (m, 2H), 2.47-2.35 (m, 1H), 2.28-2.16 (m, 1H), 2.14-2.10 (m, 3H), 1.50 (s, 9H). MS (M+H)+: 486.3.

Provenance & Evidence