Potassium Carbonate → 6'-(1H-indazol-4-yl)dispiro[1,3-oxazole-4,4'-chromene-3',3''-oxetan]-2-amine

HRID 594902Notes

Reaction equation

HRID 594902 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:31](=[CH:32][CH:33]=1)[O:30][CH2:29][C:25]1([CH2:28][O:27][CH2:26]1)[C:5]12[CH2:9][O:8][C:7]([N:10](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)=[N:6]1.O1CCOCC1.[NH:40]1[C:48]2[C:43](=[C:44](B(O)O)[CH:45]=[CH:46][CH:47]=2)[CH:42]=[N:41]1.C([O-])([O-])=O.[K+].[K+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[NH:40]1[C:48]2[C:43](=[C:44]([C:2]3[CH:3]=[C:4]4[C:31](=[CH:32][CH:33]=3)[O:30][CH2:29][C:25]3([CH2:28][O:27][CH2:26]3)[C:5]34[CH2:9][O:8][C:7]([NH2:10])=[N:6]3)[CH:45]=[CH:46][CH:47]=2)[CH:42]=[N:41]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 441183101H-Indazole-4-boronic acidHCID 86724239Di-tert-butyl (6'-bromodispiro[1,3-oxazole-4,4'-chromene-3',3''-oxetan]-2-yl)imidodicarbonate

Product 1

HCID 867243066'-(1H-indazol-4-yl)dispiro[1,3-oxazole-4,4'-chromene-3',3''-oxetan]-2-amineYield 68.6%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

Under argon atmosphere, to a mixture of di-tert-butyl (6′-bromodispiro[1,3-oxazole-4,4′-chromene-3′,3″-oxetan]-2-yl)imidodicarbonate (300 mg, 0.571 mmol), dioxane (3.0 mL) and water (1.5 mL) were added 1H-indazol-4-ylboronic acid (185 mg, 1.14 mmol), K2CO3 (237 mg, 1.71 mmol) and bis(triphenylphosphine)palladium(II) dichloride (40 mg, 0.057 mmol), and the mixture was stirred for 3 hours at 100° C. The reaction mixture was cooled down to ambient temperature, partitioned between H2O and 10% MeOH in CHCl3. The organic layer was dried over Na2SO4 and filtered, and the filtrate was concentrated at reduced pressure. The residue was dissolved with dioxane (3.0 mL), and silica gel (neutral; 900 mg) was added to the mixture. After stirring for 2.5 hours at 110° C., the reaction mixture was cooled down to ambient temperature, and concentrated at reduced pressure. Purification of the residue with column chromatography on silica gel (CHCl3-EtOH, a linear gradient of EtOH from 0 to 20%) afforded 6′-(1H-indazol-4-yl)dispiro[1,3-oxazole-4,4′-chromene-3′,3″-oxetan]-2-amine (142 mg).

Workup

  1. temperatureThe reaction mixture was cooled down to ambient temperature
  2. custompartitioned between H2O and 10% MeOH in CHCl3
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated at reduced pressure
  6. dissolutionThe residue was dissolved with dioxane (3.0 mL), and silica gel (neutral; 900 mg)
  7. additionwas added to the mixture
  8. stirringAfter stirring for 2.5 hours at 110° C.
  9. temperaturethe reaction mixture was cooled down to ambient temperature
  10. concentrationconcentrated at reduced pressure
  11. customPurification of the residue with column chromatography on silica gel (CHCl3-EtOH

Sources & evidence

ORD record
ord-b4b0554efa94429c80fd0a14bd0c6121
Source dataset
uspto-grants-2016_01
Patent number
US09242973B2

Reaction notes

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