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

HRID 527811노트

반응식

HRID 527811 반응식
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

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
50 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-068379d7a6284a46baec3a33b235b521
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346806B2

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