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

HRID 1976697Notes

Reaction equation

HRID 1976697 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([CH3:14])([CH3:13])[C:9]([O:11][CH3:12])=[O:10])=[CH:4][C:3]=1I.[CH2:16]([O:23][CH2:24][C@@H:25]([CH3:35])[C:26]#[C:27][Si:28]([CH2:33][CH3:34])([CH2:31][CH3:32])[CH2:29][CH3:30])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.CN(C)C=O>[CH2:16]([O:23][CH2:24][C@H:25]([C:26]1[C:3]2[C:2](=[N:7][CH:6]=[C:5]([C:8]([CH3:14])([CH3:13])[C:9]([O:11][CH3:12])=[O:10])[CH:4]=2)[NH:1][C:27]=1[Si:28]([CH2:33][CH3:34])([CH2:29][CH3:30])[CH2:31][CH3:32])[CH3:35])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 11323707(S)-(4-benzyloxy-3-methylbut-1-ynyl)triethylsilaneHCID 15887215Methyl 2-(6-amino-5-iodopyridin-3-yl)-2-methylpropanoate

Product 1

HCID 15887216methyl (S)-2-[3-(2-benzyloxy-1-methylethyl)-2-triethylsilyl-1H-pyrrolo[2,3-b]pyridin-5-yl]-2-methylpropanoateYield 88.3%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A vigorously stirred suspension of methyl 2-(6-amino-5-iodopyridin-3-yl)-2-methylpropanoate (4.61 g, 14.4 mmol), (S)-(4-benzyloxy-3-methylbut-1-ynyl)triethylsilane (4.98 g, 17.3 mmol), Pd(dppf)Cl2·CH2Cl2 (0.59 g, 0.72 mmol) LiCl (0.61 g, 14.4 mmol), Na2CO3 (3.82 g, 36.0 mmol) and N,N-dimethylformamide (60 mL) was degassed via three vacuum/nitrogen ingress cycles and the resulting mixture was heated at approximately 90° C. overnight. After cooling to ambient temperature, the reaction mixture was diluted with ethyl acetate and filtered through celites washing copiously with ethyl acetate. The filtrate was poured into water and extracted with ethyl acetate (x3). The combined organic extract was washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (gradient elution; 20-25% ethyl acetate/hexanes as eluent) to give the title compound as a viscous oil (6.11 g).

Workup

  1. customwas degassed via three vacuum/nitrogen ingress cycles
  2. temperatureAfter cooling to ambient temperature
  3. additionthe reaction mixture was diluted with ethyl acetate
  4. filtrationfiltered through celites
  5. washwashing copiously with ethyl acetate
  6. additionThe filtrate was poured into water
  7. extractionextracted with ethyl acetate (x3)
  8. extractionThe combined organic extract
  9. washwas washed with brine
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by flash chromatography on silica gel (gradient elution; 20-25% ethyl acetate/hexanes as eluent)

Sources & evidence

ORD record
ord-e29b8654a1e94df6acf6d1750539a258
Source dataset
uspto-grants-2001_05
Patent number
US06228867B1

Reaction notes

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