1,4-Dioxane → HCID 86709321, compound

HRID 529408Notes

Reaction equation

HRID 529408 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:15]3([CH2:21][CH2:20][O:19][CH2:18][C:17]([NH2:22])=[N:16]3)[C:14]3[CH:13]=[C:12]([Cl:23])[N:11]=[CH:10][C:9]=3[O:8][C:5]2=[CH:6][CH:7]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:32][C:33]1[C:38](B(O)O)=[CH:37][CH:36]=[CH:35][N:34]=1.O1CCOCC1>C(C1C(C(C)(C)C)=C([Pd]Cl)C=CC=1N(C)C)(C)(C)C.O>[Cl:23][C:12]1[N:11]=[CH:10][C:9]2[O:8][C:5]3[C:4]([C:15]4([CH2:21][CH2:20][O:19][CH2:18][C:17]([NH2:22])=[N:16]4)[C:14]=2[CH:13]=1)=[CH:3][C:2]([C:38]1[C:33]([F:32])=[N:34][CH:35]=[CH:36][CH:37]=1)=[CH:7][CH:6]=3

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 27832702-Fluoropyridine-3-boronic acidHCID 86709320HCID 86709320, compound

Product 1

HCID 86709321HCID 86709321, compound

Reagents, catalysts & solvents 2

HCID 178482903HCID 178482903, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

To a vial was added (E)-7-bromo-3-chloro-6′,7′-dihydro-2′H-spiro[chromeno[2,3-c]pyridine-5,5′-[1,4]oxazepin]-3′-amine (80 mg, 0.203 mmol), potassium phosphate (129 mg, 0.608 mmol), 2-fluoropyridin-3-ylboronic acid (30.0 mg, 0.213 mmol), 1,1-bis[(di-t-butyl-p-dimethylaminophenyl]palladium(ii) chloride (7.18 mg, 10.14 μmol), dioxane (1014 μL), water (338 μL). The resulting mixture was purged with N2 gas and heated at 90° C. in microwave reactor for 25 mins. It was diluted with water and extracted into EtOAc. The organic extract was washed with saturated NaCl aqueous solution, dried over MgSO4, filtered and concentrated to give the crude material as a orange solid. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a gold Redi-Sep pre-packed silica gel column (12 g), eluting with a gradient of 50% to 80% DCM/MeOH/NH4OH (90/10/1) in 40% EtOAc in Heptane, to provide (E)-3-chloro-7-(2-fluoropyridin-3-yl)-6′,7′-dihydro-2′H-spiro[chromeno[2,3-c]pyridine-5,5′-[1,4]oxazepin]-3′-amine as off-white solid.

Workup

  1. customThe resulting mixture was purged with N2 gas
  2. additionIt was diluted with water
  3. extractionextracted into EtOAc
  4. extractionThe organic extract
  5. washwas washed with saturated NaCl aqueous solution
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give the crude material as a orange solid
  10. customThe crude material was absorbed onto a plug of silica gel
  11. custompurified by chromatography through a gold Redi-Sep pre-packed silica gel column (12 g)
  12. washeluting with a gradient of 50% to 80% DCM/MeOH/NH4OH (90/10/1) in 40% EtOAc in Heptane

Sources & evidence

ORD record
ord-6c9e099af5124310872d3e4e7cf4d1c8
Source dataset
uspto-grants-2016_05
Patent number
US09346827B2

Reaction notes

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