Diisopropylethylamine → 3-(2-Chloro-3-((4-(2-ethylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenethoxy)-N-(2,2-dimethoxyethyl)-N-ethylpropanamide

HATU (1.06 g) was added to a solution of 3-(2-chloro-3-((4-(2-ethylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenethoxy)propanoic acid [Example 26, step e] (0.75 g), Hunig's base (1.22 mL) and N-ethyl-2,2-dimethoxyethanamine [U.S. Pat. No. 2,707,186] (0.37 g) in DMF (5 mL). The resulting dark solution was stirred overnight at RT. The reaction mixture was partitioned between ethyl acetate (25 mL) and 20% brine (25 mL). The organic layer was separated and washed with 20% brine (2×25 mL). The organic solution was evaporated and the residue purified by silica gel chromatography, gradient elution isohexane:triethylamine 95:5 to ethyl acetate:triethylamine 95:5. The fractions containing the product were combined and evaporated to give the subtitled compound as an oil. Yield 0.70 g.

1. customThe reaction mixture was partitioned between ethyl acetate (25 mL) and 20% brine (25 mL)
2. customThe organic layer was separated
3. washwashed with 20% brine (2×25 mL)
4. customThe organic solution was evaporated
5. customthe residue purified by silica gel chromatography, gradient elution isohexane:triethylamine 95:5 to ethyl acetate:triethylamine 95:5
6. additionThe fractions containing the product
7. customevaporated

ORD-Eintrag

ord-63f9233f10ef42e2b7ed9b55cd871944

Quelldatensatz

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08455483B2