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

HRID 609867Notes

Reaction equation

HRID 609867 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(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>C(OCC)(=O)C.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].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

8

Reactant 4

HCID 6344DichloromethaneHCID 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 95%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

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 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 (gradient elution; 20-25% ethyl acetate/hexanes as eluent) to give the title compound as a viscous pale yellow oil (6.11 g, 95%).

Workup

  1. temperatureAfter cooling to ambient temperature
  2. filtrationfiltered through celite®
  3. washwashing copiously with ethyl acetate
  4. additionThe filtrate was poured into water
  5. extractionextracted with ethyl acetate (×3)
  6. extractionThe combined organic extract
  7. washwas washed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography on silica gel (gradient elution; 20-25% ethyl acetate/hexanes as eluent)

Sources & evidence

ORD record
ord-f572f3aa491143b19d41e0dd584deeac
Source dataset
uspto-grants-1999_12
Patent number
US05998432

Reaction notes

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