Potassium Carbonate → HCID 86658462, compound

HRID 335805Notes

Reaction equation

HRID 335805 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[C:9]2[C@@:20]3([CH2:24][O:23][C:22]([NH2:25])=[N:21]3)[C:19]3[C:14](=[N:15][CH:16]=[C:17](C#CC4(C)COC4)[CH:18]=3)[O:13][C:10]2=[CH:11][CH:12]=1)(=O)=O.FC1C(B(O)O)=CC=CN=1.C(=O)([O-])[O-].[K+].[K+]>CO.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>[O:23]1[CH2:24][C:20]2([C:19]3[C:14](=[N:15][CH:16]=[CH:17][CH:18]=3)[O:13][C:10]3[C:9]2=[CH:8][CH:7]=[CH:12][CH:11]=3)[N:21]=[C:22]1[NH2:25]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27832702-Fluoropyridine-3-boronic acidHCID 86640736HCID 86640736, compound

Product 1

HCID 86658462HCID 86658462, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolvent

Procedure

A vial was charged with (S)-2′-amino-3-((3-methyloxetan-3-yl)ethynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazole]-7-yl trifluoromethanesulfonate (50.0 mg, 0.101 mmol), 2-fluoropyridin-3-ylboronic acid (21.33 mg, 0.151 mmol), potassium carbonate (69.7 mg, 0.505 mmol), and Pd(PPh3)4 (11.66 mg, 10.09 μmol). The vial was flushed with Ar (g), then dioxane (505 μL) and water (0.25 mL) were added in sequence. The vial was sealed and placed in a 70° C. oil for 1 hour. The mixture was diluted with EtOAc and washed with brine. The organic layer was dried over sodium sulfate, filtered, and evaporated. The residue was chromatographed on a 12-g Redi-Sep column with 0-60% of a 90:10:1 mix of DCM/MeOH/NH4OH in DCM to give a pink solid. The solid was dissolved in MeOH and loaded onto a 500-mg SCX-2 column. The column was first eluted with methanol, then with 2N ammonia in methanol to remove the product. The filtrate was evaporated to give (S)-7-(2-fluoropyridin-3-yl)-3-(3-methyloxetan-3-yl)ethynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine as pale yellow solid. Found MS: MH+=443.0.

Workup

  1. customThe vial was flushed with Ar (g)
  2. additiondioxane (505 μL) and water (0.25 mL) were added in sequence
  3. customThe vial was sealed
  4. customplaced in a 70° C.
  5. customfor 1 hour
  6. additionThe mixture was diluted with EtOAc
  7. washwashed with brine
  8. dry with materialThe organic layer was dried over sodium sulfate
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was chromatographed on a 12-g Redi-Sep column with 0-60% of a 90:10:1
  12. additionmix of DCM/MeOH/NH4OH in DCM
  13. customto give a pink solid
  14. washThe column was first eluted with methanol
  15. customwith 2N ammonia in methanol to remove the product
  16. customThe filtrate was evaporated

Sources & evidence

ORD record
ord-9d696c12b892446594683f972b45bd18
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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