(2R)-pentan-2-ol → 2-{[(1R)-1-Methylbutyl]oxy}-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

HRID 1011072ノート

反応式

HRID 1011072 の反応式
CC(C)([O-])C.[Na+].Cl[C:8]1[N:16]=[C:15]2[C:11]([N:12]=[CH:13][N:14]2[CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][O:18]2)=[C:10]([NH2:23])[N:9]=1.[CH3:24][C@@H:25]([OH:29])[CH2:26][CH2:27][CH3:28]>>[CH3:24][C@@H:25]([O:29][C:8]1[N:16]=[C:15]2[C:11]([N:12]=[CH:13][N:14]2[CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][O:18]2)=[C:10]([NH2:23])[N:9]=1)[CH2:26][CH2:27][CH3:28]

参加物

4

反応物 3

HCID 7014876(2R)-pentan-2-olHCID 127778192-Chloro-9-(tetrahydropyran-2-yl)adenineHCID 23676156Sodium t-butoxide

生成物 1

HCID 576997952-{[(1R)-1-Methylbutyl]oxy}-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

反応条件

温度
50 °C

実験手順

Sodium t-butoxide (27.3 g, 284 mmol) was added portionwise to (R)-2-pentanol (140 ml) at room temperature, the mixture was stirred until homogeneous. 2-Chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (18.0 g, 71.0 mmol) was added and the reaction mixture heated at 50° C. for 160 hours. The reaction was cooled to room temperature and partitioned between ethyl acetate (500 ml) and water (500 ml). The organic phase was washed with saturated sodium chloride solution (100 ml), dried (MgSO4), filtered and evaporated. The residue was triturated with ether and the solid material filtered. The precipitate was re-washed with ether and the filtrates combined and evaporated. The crude material (ca. 10 g) was dissolved in DMSO:methanol (1:1) and purified on a reverse phase (C18) column (330 g) using a gradient of 25-65% acetonitrile (+0.1% TFA)-water (+0.1% TFA) over 8 column volumes, the fractions were immediately neutralised with saturated aqueous sodium carbonate solution. Appropriate fractions were combined and partitioned between dichloromethane and saturated aqueous sodium hydrogen carbonate. The organic phase was dried (MgSO4), filtered and evaporated to give the title compound as a pale cream foam (5.05 g).

後処理

  1. temperatureThe reaction was cooled to room temperature
  2. custompartitioned between ethyl acetate (500 ml) and water (500 ml)
  3. washThe organic phase was washed with saturated sodium chloride solution (100 ml)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was triturated with ether
  8. filtrationthe solid material filtered
  9. washThe precipitate was re-washed with ether
  10. customevaporated
  11. dissolutionThe crude material (ca. 10 g) was dissolved in DMSO:methanol (1:1)
  12. custompurified on a reverse phase (C18) column (330 g)
  13. custompartitioned between dichloromethane and saturated aqueous sodium hydrogen carbonate
  14. dry with materialThe organic phase was dried (MgSO4)
  15. filtrationfiltered
  16. customevaporated

出典と根拠

ORDレコード
ord-cc0fdfcb945a480c84e7b3412fc17cdd
出典データセット
uspto-grants-2011_07
特許番号
US07977344B2

反応ノート

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