Cesium carbonate → 6'-(3-Chloropyridin-2-yl)aminodispiro[1,3-oxazole-4,4'-chromene-3',3''-oxetane]-2-amine

HRID 594897

Reaction equation

HRID 594897 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.[Cl:34][C:35]1[C:36]([NH2:41])=[N:37][CH:38]=[CH:39][CH:40]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1(/C=C/C(=O)/C=C/C2C=CC=CC=2)C=CC=CC=1.[Pd]>[Cl:34][C:35]1[C:36]([NH:41][C:2]2[CH:3]=[C:4]3[C:31](=[CH:32][CH:33]=2)[O:30][CH2:29][C:25]2([CH2:28][O:27][CH2:26]2)[C:5]23[CH2:9][O:8][C:7]([NH2:10])=[N:6]2)=[N:37][CH:38]=[CH:39][CH:40]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6932672-Amino-3-chloropyridineHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 86724239Di-tert-butyl (6'-bromodispiro[1,3-oxazole-4,4'-chromene-3',3''-oxetan]-2-yl)imidodicarbonate

Product 1

HCID 867242986'-(3-Chloropyridin-2-yl)aminodispiro[1,3-oxazole-4,4'-chromene-3',3''-oxetane]-2-amineYield 26.3%

Reagents, catalysts & solvents 2

HCID 15673654(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

The mixture of di-tert-butyl (6′-bromodispiro[1,3-oxazole-4,4′-chromene-3′,3″-oxetan]-2-yl)imidodicarbonate (150 mg, 0.286 mmol), 3-chloropyridin-2-amine (184 mg, 1.43 mmol), (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one-palladium (3:2) (52 mg, 0.057 mmol), di-tert-butyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (97 mg, 0.23 mmol), and Cs2CO3(279 mg, 0.857 mmol) in 1,4-dioxane (7.5 ml) was stirred for 48 hours at 100° C. The reaction mixture was cooled down to ambient temperature, and partitioned with CHCl3 and water. The organic layer was dried over Na2SO4, and filtered. The residue was dissolved in toluene, and was added silica gel (neutral), and stirred at 130° C. for 3 hours. The mixture was concentrated under reduced pressure, and purified by silica gel column chromatography (CHCl3/MeOH=100:0-85:15) to give an amorphous, which was washed with CHCl3/hexane to give 6′-(3-chloropyridin-2-yl)aminodispiro[1,3-oxazole-4,4′-chromene-3′,3″-oxetane]-2-amine (28 mg).

Workup

  1. temperatureThe reaction mixture was cooled down to ambient temperature
  2. custompartitioned with CHCl3 and water
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. dissolutionThe residue was dissolved in toluene
  6. additionwas added silica gel (neutral)
  7. stirringstirred at 130° C. for 3 hours
  8. concentrationThe mixture was concentrated under reduced pressure
  9. custompurified by silica gel column chromatography (CHCl3/MeOH=100:0-85:15)
  10. customto give an amorphous, which
  11. washwas washed with CHCl3/hexane

Sources & evidence

ORD record
ord-74e4cc55ff924317b0f8348615ee7db3
Source dataset
uspto-grants-2016_01
Patent number
US09242973B2

Linked notes

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