反应详情

A solution of HATU (0.143 g) in DMF (0.5 mL) was added to a solution of 3-(2-fluoro-3-((4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenethoxy)propanoic acid [Example 7, step d] (0.133 g), Hunig's base (0.22 mL) and N-(2,2-dimethoxyethyl)cycloheptanamine [WO 2008075025] (0.050 g) in DMF (0.5 mL). The resulting dark solution was stirred overnight at RT. The solvent was evaporated and the residue partitioned between ethyl acetate (25 mL) and 20% aqueous brine (25 mL). The organic layer was separated and washed with 20% aqueous brine (2×25 mL). The organic solution was evaporated and the residue purified by silica gel chromatography, elution gradient 65:30:5 to 47.5:47.5:5 isohexane:ethyl acetate:triethylamine. The fractions containing the product were combined and evaporated to give the subtitled compound as an oil. Yield 0.165 g.

1. customThe solvent was evaporated
2. customthe residue partitioned between ethyl acetate (25 mL) and 20% aqueous brine (25 mL)
3. customThe organic layer was separated
4. washwashed with 20% aqueous brine (2×25 mL)
5. customThe organic solution was evaporated
6. customthe residue purified by silica gel chromatography, elution gradient 65:30:5 to 47.5:47.5:5 isohexane
7. additionThe fractions containing the product
8. customevaporated