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1,3-Dibromopropane → 9-[3-(1-Azetidinyl)propyl]-2-(butyloxy)-8-(methyloxy)-9H-purin-6-amine

HRID 562717
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HRID 562717 반응식
F[C:2](F)(F)[C:3](O)=O.[CH2:8]([O:12][C:13]1[NH:14][C:15]([NH2:24])=[C:16]2[C:20]([N:21]=1)=[N:19][C:18]([O:22][CH3:23])=[N:17]2)[CH2:9][CH2:10][CH3:11].C(=O)([O-])[O-].[K+].[K+].BrCCCBr.N1CCC1.[CH2:40]([N:42]([CH2:45][CH3:46])[CH2:43]C)C>CN(C=O)C>[N:42]1([CH2:40][CH2:2][CH2:3][N:19]2[C:18]([O:22][CH3:23])=[N:17][C:16]3[C:20]2=[N:21][C:13]([O:12][CH2:8][CH2:9][CH2:10][CH3:11])=[N:14][C:15]=3[NH2:24])[CH2:43][CH2:46][CH2:45]1
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참가 물질

7

반응물 5

HCID 80011,3-DibromopropaneHCID 8471TriethylamineHCID 10422AzetidineHCID 11430Potassium CarbonateHCID 178450357HCID 178450357, 화합물

생성물 1

HCID 592526009-[3-(1-Azetidinyl)propyl]-2-(butyloxy)-8-(methyloxy)-9H-purin-6-amine수율 13.6%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

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온도
50 °C

실험 절차

2-(Butyloxy)-8-(methyloxy)-1H-purin-6-amine trifluoroacetate (100 mg, 0.285 mmol) was dissolved in DMF (1 ml) and potassium carbonate (98 mg, 0.712 mmol) was added. The reaction mixture was stirred at 50° C. under nitrogen for 1 hour and then cooled to room temperature. 1,3-Dibromopropane (0.029 ml, 0.285 mmol) was added and after stirring for a further 40 mins. azetidine (0.038 ml, 0.569 mmol) and triethylamine (0.079 ml, 0.569 mmol) in DMF (1 ml) were added. The reaction mixture was then stirred for a further 18 hours. The solvent was removed and the residue was partitioned between dichloromethane (2 ml) and water (2 ml). The layers were separated using a hydrophobic frit and the aqueous phase was re-extracted with DCM (2 ml). The combined organic extracts were concentrated and the residue was dissolved in 1:1 MeOH:DMSO (1 ml) and purified by MDAP (Method A). The product containing fractions were evaporated under a stream of nitrogen to give the title compound as a white solid (13 mg).

후처리

  1. temperaturecooled to room temperature
  2. stirringafter stirring for a further 40 mins
  3. stirringThe reaction mixture was then stirred for a further 18 hours
  4. customThe solvent was removed
  5. customthe residue was partitioned between dichloromethane (2 ml) and water (2 ml)
  6. customThe layers were separated
  7. extractionthe aqueous phase was re-extracted with DCM (2 ml)
  8. concentrationThe combined organic extracts were concentrated
  9. dissolutionthe residue was dissolved in 1:1 MeOH
  10. customDMSO (1 ml) and purified by MDAP (Method A)
  11. additionThe product containing fractions
  12. customwere evaporated under a stream of nitrogen

출처 및 근거

ORD 기록
ord-65e3cf9639404365b0a98a37027bcc32
출처 데이터셋
uspto-grants-2011_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08067426B2

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