Water → 4-[4-(4-Ethoxy-2-fluoro-phenoxy)pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid isopropyl ester

HRID 1931627ノート

反応式

HRID 1931627 の反応式
Cl[C:2]([O:4][CH:5]([CH3:7])[CH3:6])=[O:3].FC(F)(F)C(O)=O.[CH2:15]([O:17][C:18]1[CH:39]=[CH:38][C:21]([O:22][C:23]2[N:28]=[CH:27][N:26]=[C:25]3[N:29]([CH:32]4[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]4)[N:30]=[CH:31][C:24]=23)=[C:20]([F:40])[CH:19]=1)[CH3:16].C(N(C(C)C)CC)(C)C.O>ClCCl>[CH:5]([O:4][C:2]([N:35]1[CH2:36][CH2:37][CH:32]([N:29]2[C:25]3=[N:26][CH:27]=[N:28][C:23]([O:22][C:21]4[CH:38]=[CH:39][C:18]([O:17][CH2:15][CH3:16])=[CH:19][C:20]=4[F:40])=[C:24]3[CH:31]=[N:30]2)[CH2:33][CH2:34]1)=[O:3])([CH3:7])[CH3:6]

参加物

6

反応物 4

HCID 962WaterHCID 7917Isopropyl chloroformateHCID 81531DiisopropylethylamineHCID 669153124-(4-ethoxy-2-fluoro-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt2 回

生成物 1

HCID 445141074-[4-(4-Ethoxy-2-fluoro-phenoxy)pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid isopropyl ester収率 80%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

Isopropyl chloroformate (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA; 1 M in toluene; 0.079 ml, 0.079 mol) was added to a mixture of 4-(4-ethoxy-2-fluoro-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt (Intermediate 29; 28 mg, 0.078 mmol), and diisopropylethylamine (30 mg, 0.235 mmol) in dichloromethane (2 mL). The reaction mixture was stirred at room temperature overnight. Water was added to quench the reaction and the aqueous layer was extracted three times with dichloromethane. The combined organic layers were dried (sodium sulfate), filtered, evaporated and purified by flash chromatography on silica gel, eluting with 4% methanol/dichloromethane to give 4-[4-(4-ethoxy-2-fluoro-phenoxy)pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid isopropyl ester (27 mg, 80%) as a white solid. Mass spectrum MH+=444.

後処理

  1. customto quench
  2. customthe reaction
  3. extractionthe aqueous layer was extracted three times with dichloromethane
  4. dry with materialThe combined organic layers were dried (sodium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. custompurified by flash chromatography on silica gel
  8. washeluting with 4% methanol/dichloromethane

出典と根拠

ORDレコード
ord-ccc304c697684e2285c124d684373d75
出典データセット
uspto-grants-2012_05
特許番号
US08188098B2

反応ノート

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