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 1898498Notes

Reaction equation

HRID 1898498 reaction equation
[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]

Participants

6

Reactant 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

Product 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]-amideYield 75.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-d9ce0828306d459ba5f6bbcf822cc3d8
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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