反応 #617577

反応方程式

biphenyl-3-amine

tert-Butyl 2,8-diazaspiro[4.5]decane-2-carboxylate

2,4-dichloropyrimidine-5-carbonitrile

Hunig's base

→

tert-butyl 8-[2-(biphenyl-3-ylamino)-5-cyanopyrimidin-4-yl]-2,8-diazaspiro[4.5]decane-2-carboxylate

溶媒

ethyl acetate

CH2Cl2

反応条件

後処理

1. 1
   その他The solvent was removed under reduced pressure
2. 2
   workup.ADDITIONthe mixture was diluted with CH3CN (2 mL)
3. 3
   温度The mixture was then heated to 80° C. overnight
4. 4
   温度Upon cooling
5. 5
   洗浄washed with H2O
6. 6
   乾燥brine and the organic extracts were dried (Na2SO4)
7. 7
   ろ過filtered
8. 8
   濃縮concentrated in vacuo
9. 9
   その他The residue was purified by silica gel chromatography (ethyl acetate/hexanes)
10. 10
    その他provided
11. 11
    workup.ADDITIONa mixture of the two possible isomers which
12. 12
    その他was separated by the reverse phase chromatography

実験手順

tert-Butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (69 mg, 0.287 mol) was added to a cooled solution of the 2,4-dichloropyrimidine-5-carbonitrile (50 mg, 0.287 mmol) and Hunig's base (50 uL, 0.287 mmol) in CH2Cl2 (1.5 mL) and the reaction mixture was stirred for 3 hours at 0° C. The solvent was removed under reduced pressure, then the mixture was diluted with CH3CN (2 mL) and the biphenyl-3-amine (97 mg, 0.575 mol) was added. The mixture was then heated to 80° C. overnight. Upon cooling, the reaction mixture was diluted with ethyl acetate, washed with H2O and then brine and the organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (ethyl acetate/hexanes) provided a mixture of the two possible isomers which was separated by the reverse phase chromatography to afford tert-butyl 8-[2-(biphenyl-3-ylamino)-5-cyanopyrimidin-4-yl]-2,8-diazaspiro[4.5]decane-2-carboxylate. MS ESI calcd. for C30H35N6O2 [M+H]+ 511, found 511.

出典