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 1747596노트

반응식

HRID 1747596 반응식
[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]

참가 물질

5

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-bfbd084221a54d8fb6313c140f93c29e
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09150525B2

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