Triphenylphosphine → 7-(3-Amino-propenyl)-2-(4-fluoro-2-methyl-phenylamino)-1,6-dimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one

温度

60 °C

To a 50 mL round bottom flask equipped with a magnetic stir bar was added Pd2(dba)3 (38 mg, 42 μmol), triphenylphosphine (52 mg, 200 μmol) and THF (6.6 mL). The resulting solution was stirred under nitrogen for 20 minutes followed by the addition of acetic acid 1-[2-(4-fluoro-2-methyl-phenylamino)-1,6-dimethyl-9-oxo-8,9-dihydro-1H-imidazo[4,5-h]isoquinolin-7-yl]-allyl ester (0.288 mg, 0.664 mmol). The resulting red solution was stirred for 20 minutes, then sodium azide (47 mg, 0.72 mmol) was added as a solution in water (0.6 mL). The flask was sealed with a plastic cap and heated to 60° C. for 3 hours. The reaction mixture was cooled to room temperature and triphenylphosphine (165 mg, 0.63 mmol) was added. After stirring at room temperature for 7 hours, ammonium hydroxide was added (0.7 mL) and the reaction was stirred for 12 additional hours. The reaction mixture was diluted with ethyl acetate (50 mL) and the solution dried over sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by flash chromatography, eluting with MeOH:HCCl3 (10-40%) to give 7-(3-amino-propenyl)-2-(4-fluoro-2-methyl-phenylamino)-1,6-dimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one. 1H NMR (400 MHz, d6-DMSO) δ 11.24 (s, 1H), 10.62 (s, 1H), 8.1-8.0 (m, 2H), 7.77 (d, J=9 Hz, 1H), 7.71 (d, J=9 Hz, 1H), 7.6-7.5 (m, 1H), 6.6-6.45 (m, 2H), 4.18 (s, 3H), 3.75-3.65 (m, 2H), 2.36 (s, 3H), 2.30 (s, 3H); ESMS m/z: found, 392 (M+1)+.

1. customTo a 50 mL round bottom flask equipped with a magnetic stir bar
2. stirringThe resulting red solution was stirred for 20 minutes
3. customThe flask was sealed with
4. customa plastic cap
5. temperatureThe reaction mixture was cooled to room temperature
6. stirringAfter stirring at room temperature for 7 hours
7. stirringthe reaction was stirred for 12 additional hours
8. dry with materialthe solution dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe crude product was purified by flash chromatography
12. washeluting with MeOH

ORDレコード

ord-3b6733cca4e74bbc94c7ba5c5bb8f122

出典データセット

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08067395B2