Pyridine → tert-butyl ((4aS,11bR)-10-(5-chloro-3-methylpicolinamido)-3,3,11b-trimethyl-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate

Participants

Reaction Steps

To the crude tert-butyl ((11bR)-10-amino-3,3,11b-trimethyl-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate (190 mg, 0.449 mmol) from Step 4 (˜2:1 trans/cis mixture) dissolved in DMF (2 ml), was added 5-chloro-3-methylpyridine-2-carboxylic acid (92 mg, 0.538 mmol), pyridine (0.109 ml, 1.346 mmol) and HATU (256 mg, 0.673 mmol) and resulting solution was stirred for 1 hr at RT. The mixture was diluted with EtOAc (8 ml) and saturated NaHCO3 solution (3 ml). Water was added to dissolve precipitated solids. The organic layer was separated, washed with water, brine and concentrated. The residue was and purified by silica gel chromatography on 12 g RediSep Gold column using 10-70% EtOAc in heptane to afford major less polar trans-isomer tert-butyl ((4aR,11bR)-10-(5-chloro-3-methylpicolinamido)-3,3,11b-trimethyl-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate (110 mg, 0.191 mmol, 42.5% yield and more polar minor cis-isomer tert-butyl ((4aS,11bR)-10-(5-chloro-3-methylpicolinamido)-3,3,11b-trimethyl-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate (70 mg, 0.121 mmol, 27% yield).

Provenance & Evidence