Potassium Carbonate → (5S)-3-bromo-7-(3-pyridinyl)spiro[chromeno[2,3-b]pyridine-5,4'-[1,3]oxazol]-2'-amine

HRID 335848Notes

Reaction equation

HRID 335848 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.[N:22]1[CH:27]=[CH:26][CH:25]=[C:24](B(O)O)[CH:23]=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:24]4[CH:23]=[N:22][CH:27]=[CH:26][CH:25]=4)[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27343783-Pyridinylboronic acidHCID 58466209(S)-3-bromo-7-iodo-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

Product 1

HCID 67241561(5S)-3-bromo-7-(3-pyridinyl)spiro[chromeno[2,3-b]pyridine-5,4'-[1,3]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 (906 mg, 1.978 mmol), pyridin-3-ylboronic acid (267 mg, 2.176 mmol), potassium carbonate (1367 mg, 9.89 mmol), and tetrakis(triphenylphosphine)palladium(0) (114 mg, 0.099 mmol). The vial was flushed with argon and dioxane (9.89 mL) and water (5.1 mL) were added in sequence. The vial was sealed and placed in an 80° C. oil bath for 4 h. The mixture was cooled to rt, diluted with EtOAc (45 mL), and brine (45 mL). The layers were separated, and the aq. layer was extracted with EtOAc (2×35 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on a 40-g Redi-Sep column, eluting with 0-60% of a 90:10:1 mix of CH2Cl2/MeOH/NH4OH in CH2Cl2 to give (S)-3-bromo-7-(pyridin-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 argon and dioxane (9.89 mL) and water (5.1 mL)
  2. additionwere added in sequence
  3. customThe vial was sealed
  4. customplaced in an 80° C.
  5. customfor 4 h
  6. additiondiluted with EtOAc (45 mL), and brine (45 mL)
  7. customThe layers were separated
  8. extractionthe aq. layer was extracted with EtOAc (2×35 mL)
  9. dry with materialThe combined organic extracts were dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  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 CH2Cl2/MeOH/NH4OH in CH2Cl2

Sources & evidence

ORD record
ord-26ad3d1482b5415d9d9199c38d155b75
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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