4-(tert-Butyl)-2-(tributylstannyl)pyridine → 2-(4-tert-butyl-pyridin-2-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide

HRID 1898584ノート

反応式

HRID 1898584 の反応式
[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9](=[O:35])[C@H:10]([NH:14][C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23](Br)[N:24]=3)[N:19]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[CH:18]=2)=[O:16])[CH:11]2[CH2:13][CH2:12]2)[CH2:5][CH2:4]1)#[N:2].[C:36]([C:40]1[CH:45]=[CH:44][N:43]=[C:42]([Sn](CCCC)(CCCC)CCCC)[CH:41]=1)([CH3:39])([CH3:38])[CH3:37]>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](=[O:35])[C@H:10]([NH:14][C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([C:42]4[CH:41]=[C:40]([C:36]([CH3:39])([CH3:38])[CH3:37])[CH:45]=[CH:44][N:43]=4)[N:24]=3)[N:19]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[CH:18]=2)=[O:16])[CH:11]2[CH2:13][CH2:12]2)[CH2:5][CH2:4]1)#[N:2]

参加物

6

反応物 2

HCID 575166314-(tert-Butyl)-2-(tributylstannyl)pyridineHCID 866578732-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide

生成物 1

HCID 673859122-(4-tert-butyl-pyridin-2-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide収率 65%

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
90 °C

実験手順

In a round-bottomed flask 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide (95 mg, 0.17 mmol) and 4-tert-butyl-2-(tributylstannyl)pyridine (141 mg, 0.20 mmol) were dissolved in DMF (1.6 mL). The reaction mixture was evacuated and backfilled with Argon. Tetrakis(triphenylphosphine)palladium(0) (10 mg, 0.009 mmol) and copper (I) iodide (7 mg, 0.037 mmol) were added. The reaction mixture was stirred at 90° C. overnight. The reaction mixture was cooled to room temperature, quenched with 5 mL water and extracted with 50 mL diethyl ether (2×). The combined organic layers were washed twice with 5 mL water and once with 5 mL brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over 24 g SiO2 with MeOH/CH2Cl2/0.5% NH4OH (gradient: 0-2% MeOH). All fractions containing product were combined and concentrated to provide 68 mg (59%) of 2-(4-tert-butyl-pyridin-2-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide.

後処理

  1. customThe reaction mixture was evacuated
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customquenched with 5 mL water
  4. extractionextracted with 50 mL diethyl ether (2×)
  5. washThe combined organic layers were washed twice with 5 mL water and once with 5 mL brine
  6. dry with materialthen dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was chromatographed over 24 g SiO2 with MeOH/CH2Cl2/0.5% NH4OH (gradient: 0-2% MeOH)
  10. additionAll fractions containing product
  11. concentrationconcentrated

出典と根拠

ORDレコード
ord-403f95bcd4e54adc9c7c30f6a442f0a2
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…