2-Bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]amide → 2-(6-tert-butyl-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide

HRID 246028ノート

反応式

HRID 246028 の反応式
[C:1]([C:5]1[CH:13]=[C:12]2[C:8]([C:9]([Sn](CCCC)(CCCC)CCCC)=[N:10][N:11]2[CH3:14])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[C:28]([CH:30]1[CH2:33][N:32]([C:34](=[O:58])[C@H:35]([NH:37][C:38]([C:40]2[C:48]3[C:43](=[N:44][CH:45]=[C:46](Br)[N:47]=3)[N:42]([CH2:50][O:51][CH2:52][CH2:53][Si:54]([CH3:57])([CH3:56])[CH3:55])[CH:41]=2)=[O:39])[CH3:36])[CH2:31]1)#[N:29]>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:28]([CH:30]1[CH2:31][N:32]([C:34](=[O:58])[C@H:35]([NH:37][C:38]([C:40]2[C:48]3[C:43](=[N:44][CH:45]=[C:46]([C:9]4[C:8]5[C:12](=[CH:13][C:5]([C:1]([CH3:2])([CH3:3])[CH3:4])=[CH:6][CH:7]=5)[N:11]([CH3:14])[N:10]=4)[N:47]=3)[N:42]([CH2:50][O:51][CH2:52][CH2:53][Si:54]([CH3:57])([CH3:56])[CH3:55])[CH:41]=2)=[O:39])[CH3:36])[CH2:33]1)#[N:29]

参加物

6

反応物 2

HCID 584386122-Bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]amideHCID 712801066-tert-butyl-1-methyl-3-tributylstannanyl-1H-indazole

生成物 1

HCID 712889062-(6-tert-butyl-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide収率 85%

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

To a solution of 6-tert-butyl-1-methyl-3-tributylstannyl-1H-indazole (crude from Step 5, 217 mg, 0.45 mmol) and 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide (125 mg, 0.25 mmol) in DMF (1.5 mL) were added Pd(PPh3)4 (14 mg, 0.012 mmol) and copper(I) iodide (9 mg, 0.05 mmol). The yellow reaction mixture was purged with argon then heated at 80° C. for 1.5 h then cooled to room temperature, quenched with sat NH4Cl and extracted with EtOAc (2×). The combined organics were washed with sat LiCl and brine then dried over MgSO4 and concentrated. The crude residue was purified by silica gel chromatography with 50% to 100% EtOAc/heptane to isolate 129 mg (85%) of 2-(6-tert-butyl-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide as a white solid.

後処理

  1. customThe yellow reaction mixture was purged with argon
  2. temperaturethen cooled to room temperature
  3. customquenched with sat NH4Cl
  4. extractionextracted with EtOAc (2×)
  5. washThe combined organics were washed with sat LiCl and brine
  6. dry with materialthen dried over MgSO4
  7. concentrationconcentrated
  8. customThe crude residue was purified by silica gel chromatography with 50% to 100% EtOAc/heptane

出典と根拠

ORDレコード
ord-18c7db87151e41bd900ecdc9360d8162
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…