Bicarbonate Ion → 1-(5-(5-fluoro-2-(quinolin-6-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)cyclobutanol

HRID 2362699Notes

Reaction equation

HRID 2362699 reaction equation
[F:1][C:2]1[C:3]([C:22]2[S:26][C:25]([C:27]3([OH:31])[CH2:30][CH2:29][CH2:28]3)=[N:24][CH:23]=2)=[C:4]2[CH:10]=[C:9](I)[N:8]([S:12]([C:15]3[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:5]2=[N:6][CH:7]=1.[N:32]1[C:41]2[C:36](=[CH:37][C:38](B(O)O)=[CH:39][CH:40]=2)[CH:35]=[CH:34][CH:33]=1.C(=O)(O)[O-]>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>[F:1][C:2]1[C:3]([C:22]2[S:26][C:25]([C:27]3([OH:31])[CH2:30][CH2:29][CH2:28]3)=[N:24][CH:23]=2)=[C:4]2[CH:10]=[C:9]([C:38]3[CH:37]=[C:36]4[C:41](=[CH:40][CH:39]=3)[N:32]=[CH:33][CH:34]=[CH:35]4)[N:8]([S:12]([C:15]3[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 769Bicarbonate IonHCID 4192671Quinolin-6-ylboronic Acid (contains varying amounts of Anhydride)HCID 670034821-(5-(5-fluoro-2-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)cyclobutanol

Product 1

HCID 670035361-(5-(5-fluoro-2-(quinolin-6-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)cyclobutanol

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred ambient solution of 1-(5-(5-fluoro-2-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)cyclobutanol (Example 59A) (200 mg, 0.351 mmol) and quinoline-6-boronic acid (91 mg, 0.527 mmol) in N,N-dimethylformamide (2.63 mL) was added saturated aqueous bicarbonate solution (880 μL) followed by bis(triphenylphosphine)palladium dichloride (17.26 mg, 0.025 mmol). The mixture was heated to 70° C. for 16 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. MS ESI(+) m/z 571.1 [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-96e65509314e4902b0f9195080e5c761
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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