Sodium Carbonate → Methyl (S)-2-[3-(2-benzyloxy-1-methylethyl)-2-(3,5-dimethylphenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-2-methylpropanoate

HRID 1872916Notes

Reaction equation

HRID 1872916 reaction equation
[CH2:1]([O:8][CH2:9][C@H:10]([C:12]1[C:20]2[C:15](=[N:16][CH:17]=[C:18]([C:21]([CH3:27])([CH3:26])[C:22]([O:24][CH3:25])=[O:23])[CH:19]=2)[NH:14][C:13]=1I)[CH3:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[C:30]1[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][C:31]=1B(O)O.[C:40]([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CO.C(OCC)(=O)C>[CH2:1]([O:8][CH2:9][C@H:10]([C:12]1[C:20]2[C:15](=[N:16][CH:17]=[C:18]([C:21]([CH3:27])([CH3:26])[C:22]([O:24][CH3:25])=[O:23])[CH:19]=2)[NH:14][C:13]=1[C:35]1[CH:30]=[C:31]([CH3:40])[CH:32]=[C:33]([CH3:36])[CH:34]=1)[CH3:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2734347(2,5-Dimethylphenyl)boronic acidHCID 15887217Methyl (S)-2-[3-(2-benzyloxy-1-methylethyl)-2-iodo-1H-pyrrolo[2,3-b]pyridin-5-yl]-2-methylpropanoate

Product 1

HCID 15887218Methyl (S)-2-[3-(2-benzyloxy-1-methylethyl)-2-(3,5-dimethylphenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-2-methylpropanoateYield 100%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21867641Toluene methanolSolvent

Conditions

Temperature
80 °C

Procedure

A vigorously stirred suspension of methyl (S)-2-[3-(2-benzyloxy-1-methylethyl)-2-iodo-1H-pyrrolo[2,3-b]pyridin-5-yl]-2-methylpropanoate (4.00 g, 8.12 mmol), 2,5-dimethylphenylboronic acid (1.83 g, 12.2 mmol) and Pd(dppf)Cl2 ·CH2Cl2 (0.33 g, 0.406 mmol) in toluene/MeOH (5:2; 140 mL) was degassed via three vacuum/nitrogen ingress cycles and the resulting mixture was heated to approximately 80° C. 1M Na2CO3 (20.3 mL, 20.3 mmol) was added dropwise via syringe and the resulting mixture maintained at reflux overnight. After cooling to ambient temperature, the reaction mixture was diluted with ethyl acetate and filtered through celite® washing copiously with ethyl acetate. The filtrate was poured into water and extracted with ethyl acetate (×3). The combined organic extract was washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (25% ethyl acetate/hexanes as eluent) to afford the title compound as a colourless foam (3.82 g).

Workup

  1. customwas degassed via three vacuum/nitrogen ingress cycles
  2. temperaturethe resulting mixture maintained
  3. temperatureat reflux overnight
  4. temperatureAfter cooling to ambient temperature
  5. filtrationfiltered through celite®
  6. washwashing copiously with ethyl acetate
  7. additionThe filtrate was poured into water
  8. extractionextracted with ethyl acetate (×3)
  9. extractionThe combined organic extract
  10. washwas washed with brine
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by flash chromatography on silica gel (25% ethyl acetate/hexanes as eluent)

Sources & evidence

ORD record
ord-d7ee2727c9d64eb986b39f744415a26b
Source dataset
uspto-grants-2000_08
Patent number
US06110931

Reaction notes

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