Potassium Carbonate → 2-(1-ethyl-1H-pyrazol-4-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2,2-dimethyl-1-(pyrrolidine-1-carbonyl)-propyl]-amide

HRID 1898498ノート

反応式

HRID 1898498 の反応式
[CH3:1][C:2]([CH3:33])([CH3:32])[C@@H:3]([NH:11][C:12]([C:14]1[C:22]2[C:17](=[N:18][CH:19]=[C:20](Br)[N:21]=2)[N:16]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[CH:15]=1)=[O:13])[C:4]([N:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1)=[O:5].[CH2:34]([N:36]1[CH:40]=[C:39](B2OC(C)(C)C(C)(C)O2)[CH:38]=[N:37]1)[CH3:35].C([O-])([O-])=O.[K+].[K+]>COCCOC.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>[CH3:1][C:2]([CH3:33])([CH3:32])[C@@H:3]([NH:11][C:12]([C:14]1[C:22]2[C:17](=[N:18][CH:19]=[C:20]([C:39]3[CH:38]=[N:37][N:36]([CH2:34][CH3:35])[CH:40]=3)[N:21]=2)[N:16]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[CH:15]=1)=[O:13])[C:4]([N:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1)=[O:5]

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 113790451-Ethyl-1H-pyrazole-4-boronic acid, pinacol esterHCID 866578692-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2,2-dimethyl-1-(pyrrolidine-1-carbonyl)-propyl]-amide

生成物 1

HCID 673867412-(1-ethyl-1H-pyrazol-4-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2,2-dimethyl-1-(pyrrolidine-1-carbonyl)-propyl]-amide収率 75.2%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
90 °C

実験手順

In a pressure tube 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2,2-dimethyl-1-(pyrrolidine-1-carbonyl)-propyl]-amide (162 mg, 0.30 mmol) and 1-ethyl-1H-pyrazole-4-boronic acid pinacol ester (80 mg, 0.36 mmol) were dissolved in DME (3.0 mL). Aqueous K2CO3 (2.0 M, 0.45 mL, 0.90 mmol) and Pd(PPh3)4 (17 mg, 0.015 mmol) were added and the mixture degassed with a gentle stream of N2 for 15 min. The vial was then sealed and heated at 90° C. for 6 h. The reaction mixture was cooled to room temperature, quenched with H2O and extracted with EtOAc. The organic extracts were washed with brine, dried over MgSO4, and concentrated. The residue was purified by SiO2 chromatography (20-100% EtOAc/hexane) to afford 125 mg (75%) of 2-(1-ethyl-1H-pyrazol-4-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2,2-dimethyl-1-(pyrrolidine-1-carbonyl)-propyl]-amide as a light brown foam.

後処理

  1. customthe mixture degassed with a gentle stream of N2 for 15 min
  2. customThe vial was then sealed
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customquenched with H2O
  5. extractionextracted with EtOAc
  6. washThe organic extracts were washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe residue was purified by SiO2 chromatography (20-100% EtOAc/hexane)

出典と根拠

ORDレコード
ord-d9ce0828306d459ba5f6bbcf822cc3d8
出典データセット
uspto-grants-2013_08
特許番号
US08518945B2

反応ノート

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