Stir a solution of 4-(3-cyclopentyl-indole-1-sulfonyl)-benzoic acid (19.0 g, 51.43 mmol) in anhydrous THF (250 mL), cool to 5° C., add N-methylmorpholine (5.8 mL, 52.72 mmol) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) (9.0 g, 51.34 mmol). Stir the mixture at 0-5° C. for 1 h, add a solution of 4-aminotetrahydro-pyran (5.8 g, 57.36 mmol) in dry THF (75 mL) via dropping funnel. Bring the mixture to room temperature, stir for 3 h, and cool back down to 5° C. Stir the mixture and add 1N HCl (250 mL), add the resulting solution to a separatory funnel, and extract with ethyl acetate (250 mL). Separate the layers, wash the organic layer with brine (250 mL), and combine the aqueous layers and extract with ethyl acetate (250 mL). Combine the organics and wash with saturated aqueous sodium bicarbonate (400 mL) and dry the organic layer over sodium sulfate. Concentrate to give a foam, dissolve in minimum methylene chloride, and add to a biotage flash 65M cartridge. Elute with 3:2 hexanes/ethyl acetate to provide the major product as a foam, and dry (20 mm Hg, 40° C.) to give a white powder of pure product (20.3 g, 87%); MS (ESI) m/z 453 (m+H).
