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

HRID 1098169ノート

反応式

HRID 1098169 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[C:55]([Cl:56])=[CH:54][CH:53]=[CH:52][N:51]=3)[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[C:55]([Cl:56])=[CH:54][CH:53]=[CH:52][N:51]=3)[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

5

反応物 3

HCID 661742-Amino-5-chloropyridineHCID 16682925TrimethylaluminumHCID 59279503(2S)-methyl 3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanoate

生成物 1

HCID 57504517(2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-chloropyridin-2-yl)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanamide

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒2 回

反応条件

温度
0 °C

実験手順

Trimethylaluminium (2M in hexane) (0.455 mL, 0.91 mmol) was added to 5-chloropyridin-2-amine (112 mg, 0.87 mmol) in toluene (10 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 20 minutes. (2S)-methyl 3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanoate (Intermediate AB2) (500 mg, 0.79 mmol) in toluene (2 mL) was added and the reaction was heated to reflux for 24 hours. The reaction mixture was concentrated in vacuo and neutralised with citric acid (1M, aq) and then diluted with water (10 ml) and DCM (10 mL). The mixture was poured onto a phase separator and the organic layer collected and evaporated. The crude material was used without purification.

後処理

  1. temperaturethe reaction was heated
  2. temperatureto reflux for 24 hours
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. additiondiluted with water (10 ml) and DCM (10 mL)
  5. additionThe mixture was poured onto a phase separator
  6. customthe organic layer collected
  7. customevaporated
  8. customThe crude material was used without purification

出典と根拠

ORDレコード
ord-4d6e092f43eb46c3a464f541a691e104
出典データセット
uspto-grants-2012_03
特許番号
US08143263B2

反応ノート

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