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

HRID 2038165
ノート
印刷プレビュー

反応式

HRID 2038165 の反応式
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
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 3

HCID 11430Potassium CarbonateHCID 23000675Benzyl 3-(bromomethyl)piperidine-1-carboxylateHCID 178450370HCID 178450370、化合物2 回

生成物 1

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

試薬・触媒・溶媒 3

HCID 679Dimethyl Sulfoxide溶媒
HCID 962
Water
溶媒
HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

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:

後処理

  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

出典と根拠

ORDレコード
ord-ab210c16f3154898aaad91f7a05cd06a
出典データセット
uspto-grants-2013_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08575340B2

反応ノート

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