反応 #166000

反応方程式

CsF

DMF

3-[(2-chloro-4-iodophenyl)amino]-N-{[(2R) -2,3-dihydroxypropyl]oxy}isonicotinamide

trimethylsilylacetylene

→

desired product

3-(2-Chloro-4-ethynyl-phenylamino)-N-(2,3-dihydroxy-propoxy)-isonicotinamide

溶媒

methanol

反応条件

後処理

1. 1
   その他The solvent was then removed under reduced pressure
2. 2
   workup.ADDITIONthe residue was diluted with EtOAc
3. 3
   洗浄washed with water (2×) and saturated brine (2×)
4. 4
   乾燥The organics were dried over Na2SO4
5. 5
   ろ過filtered
6. 6
   濃縮concentrated under reduced pressure
7. 7
   その他to give a brown solid, which
8. 8
   workup.STIRRINGthe mixture was stirred at ambient temperature
9. 9
   workup.STIRRINGAfter stirring for 16 h
10. 10
    濃縮the solution was concentrated
11. 11
    洗浄the organic phase was washed with water, brine
12. 12
    乾燥dried over Na2SO4
13. 13
    ろ過filtered
14. 14
    濃縮concentrated under reduced pressure

実験手順

0.43 mmol of 3-[(2-chloro-4-iodophenyl)amino]-N-{[(2R) -2,3-dihydroxypropyl]oxy}isonicotinamide (synthesis described above), 0.02 mmol of dichlorobis(triphenylphosphine)palladium(II), and 0.03 mmol of copper (I) iodide were dissolved and DMF and TEA. 0.93 mmol of trimethylsilylacetylene was added to the stirring solution and the resultant orange mixture was vigorously stirred for 18 h at ambient temperature. The solvent was then removed under reduced pressure and the residue was diluted with EtOAc, washed with water (2×) and saturated brine (2×). The organics were dried over Na2SO4, filtered, and then concentrated under reduced pressure to give a brown solid, which was then dissolved in methanol. 3.10 mmol of CsF was added and the mixture was stirred at ambient temperature. After stirring for 16 h, the solution was concentrated, taken up in EtOAc, and then the organic phase was washed with water, brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was subjected to column chromatography (Flashmaster) on silica gel using EtOAc/MeOH (0-100%) to afford the desired product LC/MS [5.29 min; 362 (M+1)]

出典