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Potassium Carbonate → Phenylmethyl 3-{[6-amino-2-(butyloxy)-8-(methyloxy)-9H-purin-9-yl]methyl}-1-piperidinecarboxylate

HRID 2038165
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HRID 2038165 반응식
FC(F)(F)C(O)=O.[CH2:8]([O:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[C:18]([O:22][CH3:23])[NH:19]2)=[C:15]([NH2:24])[N:14]=1)[CH2:9][CH2:10][CH3:11].C(=O)([O-])[O-].[K+].[K+].Br[CH2:32][CH:33]1[CH2:38][CH2:37][CH2:36][N:35]([C:39]([O:41][CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)=[O:40])[CH2:34]1>CN(C=O)C.O.CS(C)=O>[NH2:24][C:15]1[N:14]=[C:13]([O:12][CH2:8][CH2:9][CH2:10][CH3:11])[N:21]=[C:20]2[C:16]=1[N:17]=[C:18]([O:22][CH3:23])[N:19]2[CH2:32][CH:33]1[CH2:38][CH2:37][CH2:36][N:35]([C:39]([O:41][CH2:42][C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)=[O:40])[CH2:34]1
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참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 23000675Benzyl 3-(bromomethyl)piperidine-1-carboxylateHCID 178450370HCID 178450370, 화합물2회

생성물 1

HCID 58306120Phenylmethyl 3-{[6-amino-2-(butyloxy)-8-(methyloxy)-9H-purin-9-yl]methyl}-1-piperidinecarboxylate

시약·촉매·용매 3

HCID 679Dimethyl Sulfoxide용매
HCID 962
Water
용매
HCID 6228Dimethylformamide용매

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온도
60 °C

실험 절차

To a solution of 2-(butyloxy)-8-(methyloxy)-9H-purin-6-amine trifluoroacetate salt (for example, as prepared for Intermediate 6) (2.56 g, 7.29 mmol) in DMF (60 ml) was added potassium carbonate (4.03 g, 29.1 mmol) and the mixture was left to stir at 60° C. for one hour under an atmosphere of nitrogen. The reaction mixture was then cooled to room temperature and to this was added phenylmethyl 3-(bromomethyl)-1-piperidinecarboxylate (commercially available, for example, from AniChem, or for a prep see International Patent Application Publication Number WO1999/45006) (2.275 g, 7.29 mmol). The reaction was bought back up to 50° C. and left to stir overnight. The reaction mixture was diluted with water (˜40 mL) and partitioned with a solvent mix of 1:1 ethyl acetate:DCM (40 mL). The organic layer was separated using hydrophobic frit, and was concentrated in vacuo to give pale yellow thick oil. The crude material was dissolved in 1:1 DMSO:MeOH (5 mL) and half of this solution was initially purified on reverse phase chromatography using a high pH system on a 330 g C18 silica column. The gradient used was the following:

후처리

  1. waitthe mixture was left
  2. temperatureThe reaction mixture was then cooled to room temperature
  3. customwas bought back up to 50° C.
  4. waitleft
  5. stirringto stir overnight
  6. custompartitioned with a solvent
  7. additionmix of 1:1 ethyl acetate
  8. customThe organic layer was separated
  9. concentrationwas concentrated in vacuo
  10. customto give pale yellow thick oil
  11. customMeOH (5 mL) and half of this solution was initially purified on reverse phase chromatography

출처 및 근거

ORD 기록
ord-ab210c16f3154898aaad91f7a05cd06a
출처 데이터셋
uspto-grants-2013_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08575340B2

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