Triethylamine → (2S,4S)-tert-butyl 4-(4-amino-3-((3,5-dimethoxyphenyl)ethynyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2-((tert-butyldiphenylsilyloxy)methyl)pyrrolidine-1-carboxylate

HRID 516153ノート

反応式

HRID 516153 の反応式
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:12]3[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C@H:14]([CH2:24][O:25][Si:26]([C:39]([CH3:42])([CH3:41])[CH3:40])([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH2:13]3)[N:9]=[C:10](I)[C:3]=12.[C:43]([C:45]1[CH:50]=[C:49]([O:51][CH3:52])[CH:48]=[C:47]([O:53][CH3:54])[CH:46]=1)#[CH:44].C(N(CC)CC)C.C(OCC)(=O)C>C1COCC1.[Cu]I.O>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:12]3[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C@H:14]([CH2:24][O:25][Si:26]([C:39]([CH3:42])([CH3:41])[CH3:40])([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH2:13]3)[N:9]=[C:10]([C:44]#[C:43][C:45]3[CH:46]=[C:47]([O:53][CH3:54])[CH:48]=[C:49]([O:51][CH3:52])[CH:50]=3)[C:3]=12

参加物

8

反応物 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 46613211-Ethynyl-3,5-dimethoxybenzeneHCID 89870923(2S,4S)-tert-butyl 4-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2-((tert-butyldiphenylsilyloxy)methyl)pyrrolidine-1-carboxylate

生成物 1

HCID 89870990(2S,4S)-tert-butyl 4-(4-amino-3-((3,5-dimethoxyphenyl)ethynyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2-((tert-butyldiphenylsilyloxy)methyl)pyrrolidine-1-carboxylate

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
85 °C

実験手順

PdCl2(dppf)CH2Cl2 (13 mg) was added to a mixture of (2S,4S)-tert-butyl 4-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2-((tert-butyldiphenylsilyloxy)methyl)pyrrolidine-1-carboxylate (113 mg) obtained in Step 3 above, 1-ethynyl-3,5-dimethoxybenzene (52 mg), copper (I) iodide (6 mg), and triethylamine (0.4 ml) in THF (4 ml). After nitrogen purging, the mixture was stirred at 85° C. for 3 hours. Ethyl acetate and water were added to the reaction mixture to separate the organic layer. After washing with a saturated sodium chloride solution, the organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was purified by basic silica gel column chromatography (developing solvent: hexane/ethyl acetate) to obtain the title compound as a colorless, amorphous substance (100 mg). Physical properties: m/z [M+H]+ 733.3

後処理

  1. customto separate the organic layer
  2. washAfter washing with a saturated sodium chloride solution
  3. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  4. distillationthe solvent was distilled off under reduced pressure
  5. customThe resulting residue was purified by basic silica gel column chromatography (developing solvent: hexane/ethyl acetate)

出典と根拠

ORDレコード
ord-29e096ef38f942828839aec030ec0c98
出典データセット
uspto-grants-2015_08
特許番号
US09108973B2

反応ノート

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