Phenol → 8-(4-Phenoxy-bicyclo[2.2.2]oct-1-yl)-1,3-dipropyl-3,7-dihydro-purine-2,6-dione

HRID 480115노트

반응식

HRID 480115 반응식
[OH:1][C:2]12[CH2:9][CH2:8][C:5]([C:10]3[NH:18][C:17]4[C:16](=[O:19])[N:15]([CH2:20][CH2:21][CH3:22])[C:14](=[O:23])[N:13]([CH2:24][CH2:25][CH3:26])[C:12]=4[N:11]=3)([CH2:6][CH2:7]1)[CH2:4][CH2:3]2.S(OS(C(F)(F)F)(=O)=O)(C(F)(F)F)(=O)=O.[O-]S(C(F)(F)F)(=O)=O.[C:50]1(O)[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1>C(Cl)Cl.O1CCOCC1.N1C=CC=CC=1>[O:1]([C:2]12[CH2:9][CH2:8][C:5]([C:10]3[NH:18][C:17]4[C:16](=[O:19])[N:15]([CH2:20][CH2:21][CH3:22])[C:14](=[O:23])[N:13]([CH2:24][CH2:25][CH3:26])[C:12]=4[N:11]=3)([CH2:6][CH2:7]1)[CH2:4][CH2:3]2)[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1

참가 물질

8

반응물 4

HCID 996PhenolHCID 67749Trifluoromethanesulfonic anhydrideHCID 2758875TrifluoromethanesulfonateHCID 99507768-(4-hydroxybicyclo[2.2.2]octan-1-yl)-1,3-dipropyl-1H-purine-2,6(3H,7H)-dione

생성물 1

HCID 187676228-(4-Phenoxy-bicyclo[2.2.2]oct-1-yl)-1,3-dipropyl-3,7-dihydro-purine-2,6-dione수율 15.1%

시약·촉매·용매 3

HCID 1049Pyridine용매HCID 6344Dichloromethane용매3회HCID 312751,4-Dioxane용매

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온도
0 °C

실험 절차

To a solution of 60 mg of 8-(4-Hydroxy-bicyclo[2.2.2]oct-1-yl)-1,3-dipropyl-3,7-dihydro-purine-2,6-dione (Example 13a) (0.167 mmol) in CH2Cl2 (2 ml) was added 27 μL of pyridine and the reaction mixture cooled to 0° C. To this was added 40 μL of triflic anhydride (0.24 mmol) in CH2Cl2 (1 ml). Maintained at 10° C. overnight. The reaction mixture was diluted with CH2Cl2 (5 ml) and washed with cold 1N HCl, sat'd NaHCO3 and brine. Dried over sodium sulfate and concentrated in vacuo to afford a yellow oil. The crude triflate was dissolved in 1,4-dioxane (3 ml) and 100 mg of phenol (1.08 mmol was added followed by heating at 80° C. overnight. The reaction mixture was concentrated down and the residue taken up in ethyl acetate (10 ml) washed with 1N KOH (5 ml), sat'd NaHCO3 (5 ml), 1N HCl (5 ml) and brine. The organic layer was dried over NaSO4 and concentrated in vacuo to a colorless oil which was purified by column chromatography (SiO2, 1:1 hexanes/EtOAc) to afford 11 mg of title compound as a white solid (MH+=437.29). The following compounds were prepared in an analogous manner after saponification of the methyl ester.

후처리

  1. temperatureMaintained at 10° C. overnight
  2. washwashed with cold 1N HCl
  3. dry with materialDried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customto afford a yellow oil
  6. temperatureby heating at 80° C. overnight
  7. concentrationThe reaction mixture was concentrated down
  8. washwashed with 1N KOH (5 ml), sat'd NaHCO3 (5 ml), 1N HCl (5 ml) and brine
  9. dry with materialThe organic layer was dried over NaSO4
  10. concentrationconcentrated in vacuo to a colorless oil which
  11. customwas purified by column chromatography (SiO2, 1:1 hexanes/EtOAc)

출처 및 근거

ORD 기록
ord-006f90f0050f4ff7b6fd40b6e2a8c2da
출처 데이터셋
uspto-grants-2003_11
특허 번호
US06649600B1

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