2-bromo-N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide → N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(6-fluoro-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

HRID 246782ノート

反応式

HRID 246782 の反応式
Br[C:2]1[N:7]=[C:6]2[C:8]([C:30]([NH:32][C:33]([CH3:44])([CH3:43])[CH2:34][O:35][Si:36]([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37])=[O:31])=[CH:9][N:10]([C:11]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:5]2=[N:4][CH:3]=1.[F:45][C:46]1[CH:54]=[C:53]2[C:49]([C:50]([Sn](CCCC)(CCCC)CCCC)=[N:51][NH:52]2)=[CH:48][CH:47]=1>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[Si:36]([O:35][CH2:34][C:33]([NH:32][C:30]([C:8]1[C:6]2=[N:7][C:2]([C:50]3[C:49]4[C:53](=[CH:54][C:46]([F:45])=[CH:47][CH:48]=4)[NH:52][N:51]=3)=[CH:3][N:4]=[C:5]2[N:10]([C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:9]=1)=[O:31])([CH3:43])[CH3:44])([C:39]([CH3:41])([CH3:40])[CH3:42])([CH3:38])[CH3:37]

参加物

6

反応物 2

HCID 866780042-bromo-N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamideHCID 1784482326-fluoro-3-(tributylstannyl)-1H-indazole

生成物 1

HCID 71279668N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(6-fluoro-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide収率 20.5%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418397HCID 178418397、化合物触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
85 °C

実験手順

2-Bromo-N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (287 mg, 0.674 mmol) and 6-fluoro-3-(tributylstannyl)-1H-indazole (450 mg, 0.674 mmol) were dissolved in DMF (8 mL) under nitrogen. Pd(PPh3)4 (39 mg, 0.034 mmol) and CuI (26 mg, 0.136 mmol) were added and the mixture was sonicated for 5 min while bubbling nitrogen through it. The reaction mixture was then stirred at 85° C. for 4 h. The mixture was cooled, concentrated in vacuo and then purified by chromatography (silica, petroleum ether:EtOAC 5:1 v/v) to give N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(6-fluoro-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (100 mg, 20%) as a white solid. 1H NMR (300 MHz, CD3C1): δ 8.55 (s, 1H), 8.35 (s, 1H), 8.13 (s, 1H), 8.32 (s, 1H), 7.49-7.47 (m, 3H), 7.29-7.01 (m, 15H), 3.87 (s, 2H), 1.55 (s, 6H), 0.78 (s, 9H), 0.02 (s, 6H). LC-MS: 725.3 [M+H]+.

後処理

  1. customthe mixture was sonicated for 5 min
  2. customwhile bubbling nitrogen through it
  3. temperatureThe mixture was cooled
  4. concentrationconcentrated in vacuo
  5. custompurified by chromatography (silica, petroleum ether:EtOAC 5:1 v/v)

出典と根拠

ORDレコード
ord-3f881b9c9a474acb8e01160381479a3a
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

読み込み中…