Dimethylformamide → 5,6-difluoro-N-(4-(3-(2-(pyridin-3-ylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-1H-benzo[d]imidazol-2-amine

温度

0 °C

A resealable reaction vial, under nitrogen, was charged with pyridin-3-amine (0.04 g, 42.50 mmol) and DMF (0.80 ml, 0.1 M). This was cooled to 0° C. and 60% wt in oil sodium hydride added (0.01 g, 42.50 mmol). The reaction mixture was stirred at 0° C. under a nitrogen atmosphere for 35 min. 5,6-Difluoro-N-(4-(3-(2-(methylsulfonyl)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-1H-benzo[d]imidazol-2-amine (0.04 g, 0.08 mmol) was added slowly to the mixture which was allowed to warm up to RT and stirred for 1 hr. The reaction mixture was heated to 60° C. and stirred for 1 hr. The reaction mixture was cooled to RT, then diluted with water and ethyl acetate. The layers were separated, the organic layer was dried over sodium sulfate and concentrated under reduced pressure to give oily residue, which was purified by silica prep plate (0.5% NH4OH/9.5% MeOH/Dichloromethane) followed by Gilson reverse phase chromatography (10% to 90% CH3CN/H2O/0.1% TFA) to afford 5,6-difluoro-N-(4-(3-(2-(pyridin-3-ylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-1H-benzo[d]imidazol-2-amine as a yellow solid. MS m/z=509.0 [M+H]+. Calc'd for C27H18F2N8O: 508.48.

1. customA resealable reaction vial
2. temperatureto warm up to RT
3. stirringstirred for 1 hr
4. temperatureThe reaction mixture was heated to 60° C.
5. stirringstirred for 1 hr
6. temperatureThe reaction mixture was cooled to RT
7. customThe layers were separated
8. dry with materialthe organic layer was dried over sodium sulfate
9. concentrationconcentrated under reduced pressure
10. customto give oily residue, which
11. customwas purified by silica prep plate (0.5% NH4OH/9.5% MeOH/Dichloromethane)

ORDレコード

ord-f37e1d1280f44c07af536b284371fa57

出典データセット

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07868177B2