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0 °C

2-Methyl-1-(3,4,5-trihydroxy-tetrahydro-pyran-2-yl)-propylcarbamoyl]-4-pentyl-pyrrolidine-1-carboxylic acid tert-butyl ester. To a solution of 2-(1-Amino-2-methyl-propyl)-6-propyl-tetrahydro-pyran-3,4,5-triol prepared by general method AB (51.9 mg, 0.21 mmol, 1 equiv) in dry DMF (4.5 mL) at 0° C. was added triethylamine (117 μL, 0.84 mmol, 4 equiv), followed by the addition of BSTFA (84 μL, 0.32 mmol, 1.5 equiv). The reaction mixture was stirred at 0° C. for 10 minutes, and then was stirred at rt for 45 minutes. To the reaction mixture was added the protected amino acid 7d as prepared in general method L (R9=n-pentyl, P=Boc) (72 mg, 0.25 mmol, 1.2 equiv) and HATU (120 mg, 0.32 mmol, 1.5 equiv). The reaction mixture was stirred at rt for 2 h, evaporated to dryness, taken up in Et2O (150 mL), washed with 10% citric acid (1×), saturated NaHCO3 (1×) and brine. The organic layer was dried over MgSO4 and concentrated to give the crude product (190 mg) as a yellow oil. The residue was taken up DCE (6 mL), trifluoroacetic acid (4 mL) containing water (0.2 mL) was added with stirring. The reaction mixture was stirred at rt for 1 h, then solvent was removed under vacuum by repeated co-evaporation from DCE. The residue was purified by column chromatography on silica 10% 0.25M NH3 in MeOH/DCM to give the product (38.4 mg, 43%).

1. stirringwas stirred at rt for 45 minutes
2. stirringThe reaction mixture was stirred at rt for 2 h
3. customevaporated to dryness
4. washwashed with 10% citric acid (1×), saturated NaHCO3 (1×) and brine
5. dry with materialThe organic layer was dried over MgSO4
6. concentrationconcentrated
7. customto give the crude product (190 mg) as a yellow oil
8. additionwas added
9. stirringwith stirring
10. stirringThe reaction mixture was stirred at rt for 1 h
11. customsolvent was removed under vacuum
12. customThe residue was purified by column chromatography on silica 10% 0.25M NH3 in MeOH/DCM