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

온도

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 기록

ord-b90004f28ef1403abe53965f7223eb27

출처 데이터셋

uspto-grants-2009_12

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07625880B2