1,2-Dimethoxyethane → 2-(Cyclobutyloxy)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

HRID 527811ノート

反応式

HRID 527811 の反応式
CC(C)([O-])C.[Na+].[CH:7]1([OH:11])[CH2:10][CH2:9][CH2:8]1.F[C:13]1[N:21]=[C:20]2[C:16]([N:17]=[CH:18][N:19]2[CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)=[C:15]([NH2:28])[N:14]=1.COCCOC>ClCCl>[CH:7]1([O:11][C:13]2[N:21]=[C:20]3[C:16]([N:17]=[CH:18][N:19]3[CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][O:23]3)=[C:15]([NH2:28])[N:14]=2)[CH2:10][CH2:9][CH2:8]1

参加物

6

反応物 4

HCID 80711,2-DimethoxyethaneHCID 76218CyclobutanolHCID 23676156Sodium t-butoxideHCID 592525662-Fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

生成物 1

HCID 592526272-(Cyclobutyloxy)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
50 °C

実験手順

Sodium t-butoxide (3.31 g, 34.2 mmol) was added portionwise to cyclobutanol (10 ml) at room temperature. The mixture became very thick and was heated to 50° C. 2-Fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (2 g, 8.43 mmol) was added followed by 1,2-dimethoxyethane (3 ml) and the mixture stirred at 50° C. for 90 mins. and then cooled and partitioned between ethyl acetate (50 ml) and water (50 ml). A precipitate that failed to dissolve in either phase was removed by filtration. The organic phase was separated, washed with saturated brine, dried over anhydrous magnesium sulphate, filtered and evaporated to give a cream foam. This material was dissolved in dichloromethane and purified on an aminopropyl (NH2) cartridge (110 g) using a 0-100% ethyl acetate in cyclohexane gradient followed by a 0-20% methanol (+1% triethylamine) gradient over 40 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as an off-white solid (0.655 g).

後処理

  1. temperatureand then cooled
  2. custompartitioned between ethyl acetate (50 ml) and water (50 ml)
  3. dissolutionto dissolve in either phase
  4. customwas removed by filtration
  5. customThe organic phase was separated
  6. washwashed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulphate
  8. filtrationfiltered
  9. customevaporated
  10. customto give a cream foam
  11. custompurified on an aminopropyl (NH2) cartridge (110 g)
  12. waitfollowed by a 0-20% methanol (+1% triethylamine) gradient over 40 mins
  13. customevaporated in vacuo

出典と根拠

ORDレコード
ord-068379d7a6284a46baec3a33b235b521
出典データセット
uspto-grants-2016_05
特許番号
US09346806B2

反応ノート

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