Methylamine → 3-cyclohexyl-1-methyl-1-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-urea

温度

150 °C

2-Bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine (0.328 g, 1.00 mmol) was dissolved in DMSO (2.5 mL). A solution of methylamine (33 wt % in EtOH, 2.5 mL, 20 mmol) was added and the resulting solution was heated at 150° C. in the sealed tube overnight, then cooled to RT. The reaction mixture was partitioned between EtOAc and H2O. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried (MgSO4), filtered and concentrated to give a mixture of impure Methyl-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-amine, which was dissolved in 1,2-dichloroethane (3 mL). Cyclohexylisocyanate (0.38 mL, 3.00 mmol) was added and the reaction mixture was heated to reflux overnight, cooled to RT, concentrated, purified by SiO2 chromatography (12 g SiO2, hexanes/EtOAc 0-35% EtOAc) to give 0.110 g of 3-cyclohexyl-1-methyl-1-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-urea as a yellow solid (27% yield).

1. temperaturecooled to RT
2. customThe reaction mixture was partitioned between EtOAc and H2O
3. extractionThe aqueous layer was extracted with EtOAc
4. washThe combined organic layers were washed with brine
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customto give
9. temperaturethe reaction mixture was heated
10. temperatureto reflux overnight
11. temperaturecooled to RT
12. concentrationconcentrated
13. custompurified by SiO2 chromatography (12 g SiO2, hexanes/EtOAc 0-35% EtOAc)

ORDレコード

ord-148ccf897ce640e9b01e79cdb2bab415

出典データセット

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08012974B2