Bicarbonate Ion → HCID 67003746, compound

HRID 2362708Notes

Reaction equation

HRID 2362708 reaction equation
I[C:2]1[N:20]([S:21]([C:24]2[CH:30]=[CH:29][C:27]([CH3:28])=[CH:26][CH:25]=2)(=[O:23])=[O:22])[C:5]2=[N:6][CH:7]=[CH:8][C:9]([C:10]3[S:14][C:13]([C:15]4([OH:19])[CH2:18][CH2:17][CH2:16]4)=[N:12][CH:11]=3)=[C:4]2[CH:3]=1.[F:31][C:32]1[CH:33]=[C:34]2[C:38](=[CH:39][CH:40]=1)[N:37]([CH3:41])[CH:36]=[C:35]2B1OC(C)(C)C(C)(C)O1.C(=O)(O)[O-]>CN(C)C=O.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:31][C:32]1[CH:33]=[C:34]2[C:38](=[CH:39][CH:40]=1)[N:37]([CH3:41])[CH:36]=[C:35]2[C:2]1[N:20]([S:21]([C:24]2[CH:25]=[CH:26][C:27]([CH3:28])=[CH:29][CH:30]=2)(=[O:22])=[O:23])[C:5]2=[N:6][CH:7]=[CH:8][C:9]([C:10]3[S:14][C:13]([C:15]4([OH:19])[CH2:16][CH2:17][CH2:18]4)=[N:12][CH:11]=3)=[C:4]2[CH:3]=1

Participants

6

Reactant 3

HCID 769Bicarbonate IonHCID 67003502HCID 67003502, compoundHCID 670035221350378-37-8

Product 1

HCID 67003746HCID 67003746, compound

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred ambient solution of 1-(5-(2-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)cyclobutanol (Example 107C) (150 mg, 0.272 mmol) and 5-fluoro-1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (Example 107A) (112 mg, 0.408 mmol) in N,N-dimethylformamide (2.04 mL) was added saturated aqueous bicarbonate solution (680 μL) followed by bis(triphenylphosphine) palladium dichloride (13.37 mg, 0.019 mmol). The mixture was heated to 70° C. for 3 hours and was quenched by the addition of water and dichloromethane. The layers were separated, and the aqueous layer was extracted with additional dichloromethane. The combined organics were dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give crude product. The residue was purified by flash chromatography on silica gel, eluting with a gradient of 0 to 100% ethyl acetate in hexane, to give the title compound LCMS APCI(+) m/z 602.99 [M+H]+.

Workup

  1. customwas quenched by the addition of water and dichloromethane
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with additional dichloromethane
  4. dry with materialThe combined organics were dried with anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give crude product
  8. customThe residue was purified by flash chromatography on silica gel
  9. washeluting with a gradient of 0 to 100% ethyl acetate in hexane

Sources & evidence

ORD record
ord-67ab745241f6484bb9696bd2a073d978
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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