Water → 5-(5-chloro-2-(1-methyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazole

HRID 2362743Notes

Reaction equation

HRID 2362743 reaction equation
Cl[C:2]1[C:7]([Cl:8])=[CH:6][N:5]=[C:4]2[N:9]([S:18]([C:21]3[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=3)(=[O:20])=[O:19])[C:10]([C:12]3[CH:13]=[N:14][N:15]([CH3:17])[CH:16]=3)=[CH:11][C:3]=12.C([Sn](CCCC)(CCCC)[C:33]1[S:37][CH:36]=[N:35][CH:34]=1)CCC.O>CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[Cl:8][C:7]1[C:2]([C:33]2[S:37][CH:36]=[N:35][CH:34]=2)=[C:3]2[CH:11]=[C:10]([C:12]3[CH:13]=[N:14][N:15]([CH3:17])[CH:16]=3)[N:9]([S:18]([C:21]3[CH:22]=[CH:23][C:24]([CH3:25])=[CH:26][CH:27]=3)(=[O:19])=[O:20])[C:4]2=[N:5][CH:6]=1

Participants

6

Reactant 3

HCID 962WaterHCID 27632575-(Tributylstannyl)-1,3-thiazoleHCID 670029234,5-dichloro-2-(1-methyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 670035295-(5-chloro-2-(1-methyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazole

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of Example 113C (0.148 g, 0.351 mmol) and 5-(tributylstannyl)thiazole (0.184 g, 0.492 mmol), in N,N-dimethylformamide (1.3 mL) was degassed via nitrogen sparge for 5 minutes. The reaction was treated with bis(triphenylphosphine)palladium (II) chloride (0.025 g, 0.35 mmol) and heated at 100° C. for 6 hours. The reaction was cooled to ambient temperature, treated with water (20 mL) and extracted with ethyl acetate (80 mL). The aqueous layer was extracted with additional ethyl acetate (40 mL). The combined organic layers were washed with water (2×25 mL) and brine (25 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by flash chromatography on a silica gel column, eluting with a gradient of from 0% to 50% ethyl acetae in hexanes, to provide the title compound as an off-white solid. MS ESI(+) m/z 470.2 [M+H]+.

Workup

  1. customsparge for 5 minutes
  2. temperatureThe reaction was cooled to ambient temperature
  3. extractionextracted with ethyl acetate (80 mL)
  4. extractionThe aqueous layer was extracted with additional ethyl acetate (40 mL)
  5. washThe combined organic layers were washed with water (2×25 mL) and brine (25 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe concentrate was purified by flash chromatography on a silica gel column
  10. washeluting with a gradient of from 0% to 50% ethyl acetae in hexanes

Sources & evidence

ORD record
ord-509735887a3e4adeae87c12298cbc480
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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