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

HRID 1616323
ノート
印刷プレビュー

反応式

HRID 1616323 の反応式
FC(F)(F)C(O)=O.C(NC1NC2C(N=C(OC)N=2)=C(N)N=1)CCC.C(=O)([O-])[O-].[K+].[K+].N1CCCCCC1.C(N(CC)CC)C.[CH2:45]([NH:49][C:50]1[N:58]=[C:57]2[C:53]([N:54]=[C:55]([O:71]C)[N:56]2[CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][N:64]2[CH2:70][CH2:69][CH2:68][CH2:67][CH2:66][CH2:65]2)=[C:52]([NH2:73])[N:51]=1)[CH2:46][CH2:47][CH3:48]>CN(C=O)C>[NH2:73][C:52]1[N:51]=[C:50]([NH:49][CH2:45][CH2:46][CH2:47][CH3:48])[N:58]=[C:57]2[C:53]=1[NH:54][C:55](=[O:71])[N:56]2[CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][N:64]1[CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

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 and1-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).

後処理

  1. additionwas added
  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

出典と根拠

ORDレコード
ord-92505dc8c1e24cd285356aa4e62229d8
出典データセット
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08765772B2

反応ノート

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