1-Methyl-4-(tributylstannyl)-1H-imidazole → 2-(1-methyl-1H-imidazol-4-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide

HRID 1898539ノート

反応式

HRID 1898539 の反応式
[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([C@H:11]([NH:16][C:17]([C:19]2[C:27]3[N:26]=[C:25](Br)[CH:24]=[N:23][C:22]=3[N:21]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[CH:20]=2)=[O:18])[C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)#[N:2].[CH3:37][N:38]1[CH:42]=[C:41]([Sn](CCCC)(CCCC)CCCC)[N:40]=[CH:39]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>[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([C@H:11]([NH:16][C:17]([C:19]2[C:27]3[C:22](=[N:23][CH:24]=[C:25]([C:41]4[N:40]=[CH:39][N:38]([CH3:37])[CH:42]=4)[N:26]=3)[N:21]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[CH:20]=2)=[O:18])[C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)#[N:2]

参加物

6

反応物 2

HCID 219011411-Methyl-4-(tributylstannyl)-1H-imidazoleHCID 584385322-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide

生成物 1

HCID 673864602-(1-methyl-1H-imidazol-4-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide収率 95%

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
80 °C

実験手順

In a pressure tube 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide (125 mg, 0.22 mmol) and 1-methyl-4-tributylstannanyl-1H-imidazole (97 mg, 0.26 mmol) were dissolved in DMF (2 mL). Pd(PPh3)4 (12.5 mg, 0.01 mmol) and CuI (8 mg, 0.04 mmol) were added. The tube was sealed and heated at 80° C. for 1.5 h. The reaction mixture was cooled to room temperature, quenched with H2O and extracted with EtOAc. The organic extracts were washed with saturated aqueous LiCl and brine, dried over MgSO4, and concentrated. The residue was purified by SiO2 chromatography (0-10% MeOH/EtOAc) to afford 121 mg (95%) of 2-(1-methyl-1H-imidazol-4-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide as a light brown gum.

後処理

  1. customThe tube was sealed
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customquenched with H2O
  4. extractionextracted with EtOAc
  5. washThe organic extracts were washed with saturated aqueous LiCl and brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified by SiO2 chromatography (0-10% MeOH/EtOAc)

出典と根拠

ORDレコード
ord-5491ab969cd4410582a6214be8a4d37f
出典データセット
uspto-grants-2013_08
特許番号
US08518945B2

反応ノート

読み込み中…