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Procedure: Preparation of 30 [22]

To AmberliteĀ® IRA-68 (approximately 0.05 g dried under vacuum overnight) was added the amine (0.0475 mmol) in ethyl acetate (0.6 mL) followed by the acid chloride (0.050 mmol) in ethyl acetate (0.6 mL).The reaction mixture was then shaken overnight. Water (0.1 mL) was added and the reaction shaken for an additional 30 min. Filtration and concentration of the filtrate provided the desired product 30.

Procedure: Preparation of 32 [25]

The reaction set-up and product purification procedures were carried out using the Zy-mark Benchmate Robotic Workstation.

Reaction:The variable acid (4 equiv., 0.24-0.8 mmol) was manually added to each 16 mm x 100 mm tube and the tubes were loosely capped with a polypropylene cap. The liquid handler then carried out the following steps on each tube: 1) Added 500 jiL (1.5 equiv., 0.092-0.3 mmol) of a solution of hydroxybenzotriazole in DMF 2) Added 500 |iL (1.5 equiv., 0.092-0.3 mmol) of a solution of diisopropyl carbodiimide in dichloromethane. 3) Added 500 |iL (1 equiv., 0.061-0.2 mmol) of a solution of diamine 31 in dichloromethane. 4) Washed syringe with 3 mL of dichloromethane. 5) Mixed tube contents by vortexing at speed 3 for 15 s. After all additions were complete, the workstation cycled through the tubes five times, vortexing each tube for 20 s at speed 3. The reactions were allowed to proceed until all the reactions in the run were complete (19 h), as indicated by disappearance of diamine (monitored byTLC).

Purification:The workstation carried out the following steps for each tube: 1) Conditioned a SPE column (strong cation exchange, 0.5-1.5 g sorbent, 0.6 mequiv. g-1) with 10 mL of methanol. 2) Loaded reaction contents onto the column. 3) Washed column with 2 x 10 mL of methanol. 4) Washed column with 2 mL of 0.1 M ammonia in methanol. 5) Eluted column with 2-5 mL of 1 M ammonia in methanol and collected the effluent into a tared receiving tube. Aliquots (10-20 jxL) were removed for HPLC and MS analysis.The product solutions were concentrated in vacuo and final solvent remnants were removed by further exposure to high vacuum to afford products 32.

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