Potassium Carbonate → (S)-3-bromo-7-(2-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

HRID 1970306Notes

Reaction equation

HRID 1970306 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C@:15]3([CH2:19][O:18][C:17]([NH2:20])=[N:16]3)[C:14]3[C:9](=[CH:10][CH:11]=[C:12](I)[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1.[F:22][C:23]1[C:28](B(O)O)=[CH:27][CH:26]=[CH:25][N:24]=1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:1][C:2]1[CH:3]=[C:4]2[C@:15]3([CH2:19][O:18][C:17]([NH2:20])=[N:16]3)[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:28]4[C:23]([F:22])=[N:24][CH:25]=[CH:26][CH:27]=4)[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27832702-Fluoropyridine-3-boronic acidHCID 58466209(S)-3-bromo-7-iodo-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

Product 1

HCID 67239951(S)-3-bromo-7-(2-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

A vial was charged with (S)-3-bromo-7-iodo-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (302.9 mg, 0.661 mmol), 2-fluoro-3-pyridineboronic acid (102 mg, 0.727 mmol), potassium carbonate (457 mg, 3.31 mmol), and tetrakis(triphenylphosphine)palladium(0) (38.2 mg, 0.033 mmol). The vial was flushed with Ar (g), then dioxane (3306 μL) and water (1.7 mL) were added in sequence. The vial was sealed and placed in a 75° C. oil bath for 2 hours. The mixture was diluted with EtOAc (15 mL) and brine (15 mL). The layers were separated, and the aq. layer was extracted with EtOAc (2×15 mL). The combined organic extracts were dried over sodium sulfate, filtered, and evaporated. The residue was purified by chromatography on a 40-g Redi-Sep column, eluting with 0-60% of a 90:10:1 mix of DCM/MeOH/NH4OH in DCM to give (S)-3-bromo-7-(2-fluoropyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine as an off-white solid.

Workup

  1. customThe vial was flushed with Ar (g)
  2. additiondioxane (3306 μL) and water (1.7 mL) were added in sequence
  3. customThe vial was sealed
  4. customplaced in a 75° C.
  5. customfor 2 hours
  6. additionThe mixture was diluted with EtOAc (15 mL) and brine (15 mL)
  7. customThe layers were separated
  8. extractionthe aq. layer was extracted with EtOAc (2×15 mL)
  9. dry with materialThe combined organic extracts were dried over sodium sulfate
  10. filtrationfiltered
  11. customevaporated
  12. customThe residue was purified by chromatography on a 40-g Redi-Sep column
  13. washeluting with 0-60% of a 90:10:1
  14. additionmix of DCM/MeOH/NH4OH in DCM

Sources & evidence

ORD record
ord-067b3ee889204a55acbd97328ac45c6e
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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