Sodium hydride → 6-{[(1S,3S)-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopentyl]oxy}-8-(1-naphthyl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

HRID 447603ノート

反応式

HRID 447603 の反応式
[Si:1]([O:8][CH2:9][C@H:10]1[CH2:14][CH2:13][C@H:12]([OH:15])[CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].Cl[C:19]1[N:27]=[CH:26][N:25]=[C:24]2[C:20]=1[N:21]=[C:22]([C:34]1[C:43]3[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=3)[CH:37]=[CH:36][CH:35]=1)[N:23]2[CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][O:29]1>CN(C=O)C>[Si:1]([O:8][CH2:9][C@H:10]1[CH2:14][CH2:13][C@H:12]([O:15][C:19]2[N:27]=[CH:26][N:25]=[C:24]3[C:20]=2[N:21]=[C:22]([C:34]2[C:43]4[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=4)[CH:37]=[CH:36][CH:35]=2)[N:23]3[CH:28]2[CH2:33][CH2:32][CH2:31][CH2:30][O:29]2)[CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 66797963(1S,3S)-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopentanolHCID 866187096-chloro-8-(1-naphthyl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

生成物 1

HCID 667978956-{[(1S,3S)-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopentyl]oxy}-8-(1-naphthyl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purine収率 70%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

To a solution of (1S,3S)-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-cyclopentanol (111.0 mg, 0.0004817 mol) (azeotroped with toluene) in DMF (3.6 mL) at 0° C. under an atmosphere of nitrogen was added sodium hydride (24.1 mg, 0.000602 mol). The mixture was stirred for 15 min. To this cold solution was added a solution of 6-chloro-8-(1-naphthyl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (163 mg, 0.000401 mol) in DMF (1.8 mL). The flask was rinsed with DMF (1.0 mL)) and this was added to the reaction as well. The resulting mixture was stirred for 20 h. The reaction mixture was quenched with water and the mixture was extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered and collected in vacuo. The residue was purified by flash chromatography (10 to 40% EtOAc/hexanes) to obtain 156.9 mg (70%) of the title compound as a white solid.

後処理

  1. washThe flask was rinsed with DMF (1.0 mL)) and
  2. additionthis was added to the reaction as well
  3. stirringThe resulting mixture was stirred for 20 h
  4. customThe reaction mixture was quenched with water
  5. extractionthe mixture was extracted with EtOAc (3×)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. customcollected in vacuo
  9. customThe residue was purified by flash chromatography (10 to 40% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-50e8ca2a47e34264aaf7c4029bd2868f
出典データセット
uspto-grants-2013_07
特許番号
US08481550B2

反応ノート

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