HCID 67003585, compound → HCID 67003633, compound

HRID 2362619Notes

Reaction equation

HRID 2362619 reaction equation
[Cl:1][C:2]1[C:3](I)=[C:4]2[CH:10]=[CH:9][N:8]([S:11]([C:14]3[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:5]2=[N:6][CH:7]=1.[CH3:22][O:23][CH2:24][O:25][C:26]1([C:30]2[S:31][C:32]([Sn](CCCC)(CCCC)CCCC)=[CH:33][N:34]=2)[CH2:29][CH2:28][CH2:27]1>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[C:3]([C:32]2[S:31][C:30]([C:26]3([O:25][CH2:24][O:23][CH3:22])[CH2:27][CH2:28][CH2:29]3)=[N:34][CH:33]=2)=[C:4]2[CH:10]=[CH:9][N:8]([S:11]([C:14]3[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 2

HCID 67003585HCID 67003585, compoundHCID 67003872HCID 67003872, compound

Product 1

HCID 67003633HCID 67003633, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of 5-chloro-4-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridine (Example 1D) (7.12 g, 16.46 mmol), bis(triphenylphosphine)palladium dichloride (0.809 g, 1.15 mmol), and 2-(1-(methoxymethoxy)cyclobutyl)-5-(tributylstannyl)thiazole (Example 1C) (10.45 g, 21.39 mmol) in N,N-dimethylformamide (54.9 ml) was heated to 70° C. for 1 hour. The reaction was cooled to room temperature and quenched by the addition of an aqueous potassium fluoride solution (19 g in 100 mL water) and ethyl acetate (200 mL). The mixture was stirred vigorously overnight and was then filtered through diatomaceous earth, eluting with ethyl acetate. The layers were separated, and the organic layer was washed with aqueous saturated bicarbonate solution and water. The organic layer was dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel, eluting with a gradient of 0 to 35% ethyl acetate in hexane, to afford the title compound. MS ESI(+) m/z 504 [M+H]+.

Workup

  1. customquenched by the addition of an aqueous potassium fluoride solution (19 g in 100 mL water) and ethyl acetate (200 mL)
  2. filtrationwas then filtered through diatomaceous earth
  3. washeluting with ethyl acetate
  4. customThe layers were separated
  5. washthe organic layer was washed with aqueous saturated bicarbonate solution and water
  6. dry with materialThe organic layer was dried with anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography on silica gel
  10. washeluting with a gradient of 0 to 35% ethyl acetate in hexane

Sources & evidence

ORD record
ord-e1d470f99e274dda8d7dc160a9ccde46
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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