HCID 67382699, compound → HCID 67383175, compound

HRID 335873Notes

Reaction equation

HRID 335873 reaction equation
Br[C:2]1C(F)=C2C(=CC=1)OC1=NC=C(I)C=C1C2=O.[Br:19][C:20]1[CH:21]=[C:22]2[C:32](=[CH:33][C:34]=1[F:35])[O:31][C:25]1=[N:26][CH:27]=[C:28]([I:30])[CH:29]=[C:24]1[C:23]2=O.C[Mg]Cl.BrC1C(F)=C2C(=CC=1)OC1=NC=C(I)C=C1C2=C>O1CCOCC1>[Br:19][C:20]1[CH:21]=[C:22]2[C:32](=[CH:33][C:34]=1[F:35])[O:31][C:25]1=[N:26][CH:27]=[C:28]([I:30])[CH:29]=[C:24]1[C:23]2=[CH2:2]

Participants

6

Reactant 4

HCID 67382699HCID 67382699, compoundHCID 67383001HCID 67383001, compoundHCID 67383179HCID 67383179, compoundHCID 178418332HCID 178418332, compound

Product 1

HCID 67383175HCID 67383175, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A suspension of 7-bromo-6-fluoro-3-iodo-5H-chromeno[2,3-b]pyridin-5-one and 7-bromo-8-fluoro-3-iodo-5H-chromeno[2,3-b]pyridin-5-one (1:4 mixture) (76 g, 182 mmol) in 1 L dioxane was placed under argon and was heated with a heat gun until it became a homogenous solution. The solution was allowed to cool to room temperature and stir 72 hours. The reaction mixture was then cooled to −10° C. and was treated with methylmagnesium chloride (106 mL, 319 mmol) dropwise with stirring over 30 min. After stirring for an additional 60 min, the reaction mixture was quenched with MeOH (25 mL). Water (250 mL) was added, followed by concentrated NH4Cl solution (250 mL). The reaction mixture was concentrated in vacuo to remove most of the organics. The remaining aqueous solution was extracted with EtOAc (3×500 mL). The organics were washed with brine, dried over MgSO4 and concentrated. The crude residue was taken up in ˜300 mL CH2Cl2 and was again concentrated. This process was repeated 3×. The crude black solid was triturated with MeOH and was again dried to provide a 1:10 mixture of 7-bromo-6-fluoro-3-iodo-5-methylene-5H-chromeno[2,3-b]pyridine and 7-bromo-8-fluoro-3-iodo-5-methylene-5H-chromeno[2,3-b]pyridine (59.200 g, 142 mmol, 78% yield). This material was used without purification.

Workup

  1. temperaturewas heated with a heat gun until it
  2. temperatureThe reaction mixture was then cooled to −10° C.
  3. stirringwith stirring over 30 min
  4. stirringAfter stirring for an additional 60 min
  5. customthe reaction mixture was quenched with MeOH (25 mL)
  6. additionWater (250 mL) was added
  7. concentrationThe reaction mixture was concentrated in vacuo
  8. customto remove most of the organics
  9. extractionThe remaining aqueous solution was extracted with EtOAc (3×500 mL)
  10. washThe organics were washed with brine
  11. dry with materialdried over MgSO4
  12. concentrationconcentrated
  13. concentrationwas again concentrated
  14. customThe crude black solid was triturated with MeOH
  15. customwas again dried
  16. customto provide

Sources & evidence

ORD record
ord-5efed3858236445ea9d09782d5932095
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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