Sodium Carbonate → (S)-methyl 2-((6-carbamoyl-2-(4-(4-fluorophenoxy)phenyl)pyrimidin-4-yl)amino)propanoate

温度

100 °C

To a suspension of (S)-methyl 2-((6-carbamoyl-2-chloropyrimidin-4-yl)amino)propanoate (5.133 g, 19.84 mmol) in dioxane (100 mL) was added 2-(4-(4-fluorophenoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (6.858 g, 21.83 mmol), 2M aqueous Na2CO3 (19.9 mL, 39.8 mmol) and PdCl2(dppf) (0.809 g, 0.99 mmol). The reaction vessel was flushed with argon, sealed and heated at 100° C. overnight. After cooling, the reaction mixture was diluted with 500 mL EtOAc and washed with brine (3×100 mL). The organic layer was dried over Na2SO4, filtered and chromatographed over silica gel with 20-60% acetone in hexanes. The product fractions were isolated and evaporated in vacuo to give the product (S)-methyl 2-((6-carbamoyl-2-(4-(4-fluorophenoxy)phenyl)pyrimidin-4-yl)amino)propanoate as a yellow-orange solid (4.128 g, 10.05 mmol, 51% yield). LC/MS: m/z=411.2 [M+H]+.

1. customThe reaction vessel was flushed with argon
2. customsealed
3. temperatureAfter cooling
4. additionthe reaction mixture was diluted with 500 mL EtOAc
5. washwashed with brine (3×100 mL)
6. dry with materialThe organic layer was dried over Na2SO4
7. filtrationfiltered
8. customchromatographed over silica gel with 20-60% acetone in hexanes
9. customThe product fractions were isolated
10. customevaporated in vacuo

ORDレコード

ord-df12e73f5ae3430798e6a75b9f445029

出典データセット

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09163008B2