Azepane → 6-Amino-2-(butylamino)-9-[5-(hexahydro-1h-azepin-1-yl)pentyl]-7,9-dihydro-8h-purin-8-one

HRID 562783노트

반응식

HRID 562783 반응식
FC(F)(F)C(O)=O.C(NC1NC2C(N=C(OC)N=2)=C(N)N=1)CCC.C(=O)([O-])[O-].[K+].[K+].BrCCCCCCl.N1CCCCCC1.C(N(CC)CC)C.[CH2:52]([NH:56][C:57]1[N:65]=[C:64]2[C:60]([N:61]=[C:62]([O:78]C)[N:63]2[CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][N:71]2[CH2:77][CH2:76][CH2:75][CH2:74][CH2:73][CH2:72]2)=[C:59]([NH2:80])[N:58]=1)[CH2:53][CH2:54][CH3:55]>CN(C=O)C>[NH2:80][C:59]1[N:58]=[C:57]([NH:56][CH2:52][CH2:53][CH2:54][CH3:55])[N:65]=[C:64]2[C:60]=1[NH:61][C:62](=[O:78])[N:63]2[CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][N:71]1[CH2:72][CH2:73][CH2:74][CH2:75][CH2:76][CH2:77]1

참가 물질

8

반응물 6

HCID 8119AzepaneHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 960701-Bromo-5-chloropentaneHCID 66726833n2-Butyl-9-[5-(hexahydro-1h-azepin-1-yl)pentyl]-8-(methyloxy)-9h-purine-2,6-diamineHCID 178448877HCID 178448877, 화합물

생성물 1

HCID 592526046-Amino-2-(butylamino)-9-[5-(hexahydro-1h-azepin-1-yl)pentyl]-7,9-dihydro-8h-purin-8-one

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
60 °C

실험 절차

N2-Butyl-8-(methyloxy)-3H-purine-2,6-diamine trifluoroacetate (192 mg, 0.547 mmol) and potassium carbonate (189 mg, 1.368 mmol) were suspended in DMF (3 ml) and heated to 60° C. for 1 hour. The reaction mixture was cooled to room temperature and 1-bromo-5-chloropentane (0.072 ml, 0.547 mmol) was added and the reaction stirred for a further 18 hours. Hexahydro-1H-azepine (54.2 mg, 0.547 mmol) and triethylamine (0.076 ml, 0.547 mmol) were added and the reaction mixture heated to 70° C. for 24 hours. LCMS showed a major peak with MH+404 consistent with the formation of N2-butyl-9-[5-(hexahydro-1H-azepin-1-yl)pentyl]-8-(methyloxy)-9H-purine-2,6-diamine. The solvent was removed in vacuo and the residue partitioned between DCM (2 ml) and water (2 ml). The aqueous was extracted again with DCM (2 ml) and the combined organic extracts were concentrated and the residue was dissolved in 1:1 MeOH:DMSO (2 ml) and purified by MDAP (Method C). Evaporation of the product containing fractions gave a residual TFA salt which LCMS indicated had undergone hydrolysis of the 8-methoxy group, presumably on concentration in the presence of TFA. This crude material was dissolved once more in 1:1 MeOH:DMSO (2 ml) and re-purified by MDAP (Method A). Product-containing fractions were evaporated under a stream of nitrogen to give the title compound as a white solid (39 mg).

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. temperaturethe reaction mixture heated to 70° C. for 24 hours
  3. customThe solvent was removed in vacuo
  4. customthe residue partitioned between DCM (2 ml) and water (2 ml)
  5. extractionThe aqueous was extracted again with DCM (2 ml)
  6. concentrationthe combined organic extracts were concentrated
  7. dissolutionthe residue was dissolved in 1:1 MeOH
  8. customDMSO (2 ml) and purified by MDAP (Method C)
  9. customEvaporation of the product
  10. additioncontaining fractions

출처 및 근거

ORD 기록
ord-8a8b044e92aa44cb85c83ad9cee9b40c
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08067426B2

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