Potassium Carbonate → HCID 67386580, compound

HRID 1898574Notes

Reaction equation

HRID 1898574 reaction equation
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:31])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19](Br)[N:20]=3)[N:15]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[CH:14]=2)=[O:12])[CH3:9])[CH2:4]1)#[N:2].[CH3:32][O:33][C:34]1[CH:35]=[C:36](B(O)O)[CH:37]=[C:38]([O:42][CH3:43])[C:39]=1[O:40][CH3:41].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>[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:31])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:36]4[CH:37]=[C:38]([O:42][CH3:43])[C:39]([O:40][CH3:41])=[C:34]([O:33][CH3:32])[CH:35]=4)[N:20]=3)[N:15]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[CH:14]=2)=[O:12])[CH3:9])[CH2:4]1)#[N:2]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27343903,4,5-Trimethoxybenzeneboronic acidHCID 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]amide

Product 1

HCID 67386580HCID 67386580, compoundYield 100%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

In a round-bottomed flask 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) and 3,4,5-trimethoxyphenylboronic acid (78 mg, 0.37 mmol) were dissolved in DME (2.0 mL). Aqueous K2CO3 (2.0 M, 0.37 mL, 0.74 mmol) and Pd(PPh3)4 (14 mg, 0.012 mmol) were added and the mixture degassed with a gentle stream of N2 for 15 min. The reaction mixture was heated at 90° C. for 1.5 h then 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 (50-100% EtOAc/heptane) to afford 146 mg (>100%) of 2-(3,4,5-trimethoxy-phenyl)-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 viscous colorless oil.

Workup

  1. customthe mixture degassed with a gentle stream of N2 for 15 min
  2. temperaturethen cooled to room temperature
  3. customquenched with H2O
  4. extractionextracted with EtOAc
  5. washThe organic extracts were washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified by SiO2 chromatography (50-100% EtOAc/heptane)

Sources & evidence

ORD record
ord-94d704f2eb2e4a36b1a8f5cbf3852572
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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