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2-Amino-5-chloropyridine → (2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-chloropyridin-2-yl)-2-(1-(2,3-dichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanamide

HRID 1098048
ノート
印刷プレビュー

反応式

HRID 1098048 の反応式
C[Al](C)C.[Cl:5][C:6]1[CH:7]=[CH:8][C:9]([NH2:12])=[N:10][CH:11]=1.[Si:13]([O:30][CH2:31][CH2:32][O:33][CH2:34][C@H:35]([O:40][C:41]1[N:46]=[CH:45][N:44]=[C:43]2[N:47]([C:50]3[CH:55]=[CH:54][CH:53]=[C:52]([Cl:56])[C:51]=3[Cl:57])[N:48]=[CH:49][C:42]=12)[C:36](OC)=[O:37])([C:26]([CH3:29])([CH3:28])[CH3:27])([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C1(C)C=CC=CC=1>[Si:13]([O:30][CH2:31][CH2:32][O:33][CH2:34][C@H:35]([O:40][C:41]1[N:46]=[CH:45][N:44]=[C:43]2[N:47]([C:50]3[CH:55]=[CH:54][CH:53]=[C:52]([Cl:56])[C:51]=3[Cl:57])[N:48]=[CH:49][C:42]=12)[C:36]([NH:12][C:9]1[CH:8]=[CH:7][C:6]([Cl:5])=[CH:11][N:10]=1)=[O:37])([C:26]([CH3:27])([CH3:28])[CH3:29])([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 661742-Amino-5-chloropyridineHCID 16682925TrimethylaluminumHCID 59279524(2S)-Methyl 3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(1-(2,3-dichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanoate

生成物 1

HCID 57504550(2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-chloropyridin-2-yl)-2-(1-(2,3-dichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanamide収率 95%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒2 回

実験手順

Trimethylaluminium (2M in toluene) (0.638 mL, 1.28 mmol) was added to 5-chloropyridin-2-amine (164 mg, 1.28 mmol) in toluene (2 mL) under nitrogen. The resulting solution was stirred at room temperature for 15 minutes. (2S)-Methyl 3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(1-(2,3-dichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanoate (Intermediate AR1) (425 mg, 0.64 mmol) in toluene (8 mL) was added sealed into a 20 mL microwave tube. The reaction was heated to 120° C. for 4 hours in the microwave reactor and cooled to RT. The reaction mixture was allowed to cool and concentrated in vacuo. The residue was neutralised with citric acid (1M, aq) and then diluted with water (30 mL) and extracted with EtOAc (2×50 mL). The combined organics were dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in isohexane to afford (2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-chloropyridin-2-yl)-2-(1-(2,3-dichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanamide (460 mg, 95%). m/z (ES+) (M+H)+=763; HPLC tR=3.94 min.

後処理

  1. customsealed into a 20 mL microwave tube
  2. temperatureThe reaction was heated to 120° C. for 4 hours in the microwave reactor
  3. temperaturecooled to RT
  4. temperatureto cool
  5. concentrationconcentrated in vacuo
  6. additiondiluted with water (30 mL)
  7. extractionextracted with EtOAc (2×50 mL)
  8. dry with materialThe combined organics were dried (MgSO4)
  9. customevaporated
  10. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in isohexane

出典と根拠

ORDレコード
ord-138b419f30664b6ea0320e1369cce961
出典データセット
uspto-grants-2012_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08143263B2

反応ノート

読み込み中…

このページの内容参加物実験手順後処理出典と根拠反応ノート