N N

Scheme 13 50

Procedure: Route B

Introduction of Ft'. Resin-bound amino acid ester and hydrazide:To a suspension of resin-bound N-(tert-alkoxycarbonyl)-leucine methyl ester [65] 47 (2.07 g, 1.49 mmol) in n-bu-tanol (8 mL), anhydrous hydrazine (2.0 mL) was added and the mixture was shaken at rt for 6.5 h. After filtration, the resin was washed alternately withTHF and MeOH (4 portions each). After rinsing three times with DCM and drying, the resin-bound acid hydrazide (1.95 g) was obtained.

Introduction of R2, ring formation and derivatization with R3: The resin-bound acid hydrazide (110 mg, 0.079 mmol) and a solution of benzyl isothiocyanate (57 mg, 0.38 mmol, 4.81 equiv.) in DMF (3 mL) were mixed and shaken at rt overnight. After draining off the solution, the resin was washed with DMF (3x2 mL), DCM (3x2 mL),THF (3x2 mL) and dried to afford the thiosemicarbazide resin 48 (R2 = Bn). A 3 mL volume of KOH solution (0.25 M KOH/dioxane, 2:3) was added to this resin and the mixture was heated to approx. 65° C for 3 h. After filtration, the resin was washed withTHF (3x2 mL), MeOH (3x2 mL),THF (3x2 mL) and dried to afford a triazole thiolate resin.To a suspension of this resin in a 0.16 M DIPEA/dioxane solution (1 mL) a 0.4 M methyl iodide/dioxane solution (1 mL) was added and the mixture was shaken at rt for 3 h.The reagent solution was drained off and the resin was washed withTHF (3x2 mL), MeOH (3x2 mL),THF (3x2 mL), DCM (3x2 mL) and dried to give the S-alkyl triazole resin 49 (R2 = Bn, R3 = Me).This resin was treated with 10 %TFA/DCM (2.5 mL) at rt for 4.5 h and filtered. The resin was rinsed with DCM (2x3 mL), MeOH (2x3 mL) and the filtrates were evaporated and dried to afford the trifluo-roacetate salt of SO (30 mg, 93 % crude yield from resin 47). This product may be acylat-ed in solution, as indicated in Scheme 13.

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