Cesium carbonate → HCID 86624187, compound

Participants

Reaction Conditions

Reaction Steps

To a slurry of 4-[2-(cyclopropanecarbonyl-amino)-thiazol-4-yl]-benzylamine (1.654 g, 6.052 mmol) in toluene (30.2 mL)/dioxane (7.8 mL), at 100° C., add a solid mixture of 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (1.29 g, 3.03 mmol), tris(dibenzylideneacetone)-dipalladium(0) (0.55 g, 0.61 mmol), BINAP (0.75 g, 0.12 mmol) and cesium carbonate (3.45 g, 10.6 mmol) all at once. Purge the reaction mixture with nitrogen and heat at 100° C. overnight. After cooling to room temperature, filter the reaction mixture over Celite® and wash with DCM (500 mL). Concentrate in vacuo, dissolve the residue in DCM and load on to an Analogix® column (150 g). Purify by preparative liquid chromatography (0:1 to 1:9 2M ammonia in methanol/DCM over 33 min, 1:9 to 1:3 2M ammonia in methanol/DCM over 33 min, 1:3 to 1:1 2M ammonia in methanol/DCM over 33 min; 35 mL/min) to afford 7-chloro-6-{4-[2-(cyclopropanecarbonyl-amino)-thiazol-4-yl]-benzylamino}-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.318 g, 19%) as a yellow foam. MS (ES+) m/z: 549.1 (M+H)+.

Provenance & Evidence