Potassium Phosphate, Tribasic → HCID 53390812, compound

HRID 455702Notes

Reaction equation

HRID 455702 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:15]3([N:20]=[C:19]([NH2:21])[CH2:18][O:17][CH2:16]3)[C:14]3[CH:13]=[C:12]([O:22][CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[N:11]=[C:10]([F:28])[C:9]=3[O:8][C:5]2=[CH:6][CH:7]=1.[F:29][C:30]1[C:35](B(O)O)=[CH:34][CH:33]=[CH:32][N:31]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>>[F:28][C:10]1[C:9]2[O:8][C:5]3[C:4]([C:15]4([N:20]=[C:19]([NH2:21])[CH2:18][O:17][CH2:16]4)[C:14]=2[CH:13]=[C:12]([O:22][CH2:23][C:24]([CH3:26])([CH3:27])[CH3:25])[N:11]=1)=[CH:3][C:2]([C:35]1[C:30]([F:29])=[N:31][CH:32]=[CH:33][CH:34]=1)=[CH:7][CH:6]=3

Participants

4

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27832702-Fluoropyridine-3-boronic acidHCID 67438228HCID 67438228, compound

Product 1

HCID 53390812HCID 53390812, compoundYield 89.3%

Procedure

A sealable vial was charged with 7-bromo-1-fluoro-3-(neopentyloxy)-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine (200 mg, 0.444 mmol), 2-fluoropyridin-3-ylboronic acid (125 mg, 0.888 mmol), bis[di-tert-butyl(4-dimethylaminophenyl)phosphine]dichloropalladium(II) (31.4 mg, 0.044 mmol) and potassium phosphate (283 mg, 1.332 mmol). The vial was evacuated and backfilled with nitrogen (procedure was repeated twice). Dioxane (3 mL) and water (1 mL) were added and the reaction mixture was purged for 1 min with nitrogen. The vial was placed in a preheated oilbath (100° C.) for start 1.5 h. The reaction mixture was cooled to rt and water and EtOAc were added to the reaction mixture. The organic phase was separated and dried over MgSO4. The solvent was removed under reduced pressure and the residue was purified by column chromatography (1-10% MeOH in DCM) to obtain 1-fluoro-7-(2-fluoropyridin-3-yl)-3-(neopentyloxy)-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine as a beige solid (185 mg).

Workup

  1. customThe vial was evacuated
  2. additionDioxane (3 mL) and water (1 mL) were added
  3. customthe reaction mixture was purged for 1 min with nitrogen
  4. customwas placed in a preheated oilbath (100° C.) for start 1.5 h
  5. additionwater and EtOAc were added to the reaction mixture
  6. customThe organic phase was separated
  7. dry with materialdried over MgSO4
  8. customThe solvent was removed under reduced pressure
  9. customthe residue was purified by column chromatography (1-10% MeOH in DCM)

Sources & evidence

ORD record
ord-cf1cee16db2e4a4ca0afd31051481218
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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