1,4-Dioxane → HCID 86658502, compound

HRID 335982Notes

Reaction equation

HRID 335982 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:15]3([CH:19]([CH2:20][O:21][CH3:22])[S:18][C:17]([NH2:23])=[N:16]3)[C:14]3[CH:13]=[C:12]([Cl:24])[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:33][C:34]1[C:39](B(O)O)=[CH:38][CH:37]=[CH:36][N:35]=1.O1CCOCC1>O.C(C1C(C(C)(C)C)=C([Pd]Cl)C=CC=1N(C)C)(C)(C)C>[Cl:24][C:12]1[N:11]=[CH:10][C:9]2[O:8][C:5]3[C:4]([C:15]4([CH:19]([CH2:20][O:21][CH3:22])[S:18][C:17]([NH2:23])=[N:16]4)[C:14]=2[CH:13]=1)=[CH:3][C:2]([C:39]1[C:34]([F:33])=[N:35][CH:36]=[CH:37][CH:38]=1)=[CH:7][CH:6]=3

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 27832702-Fluoropyridine-3-boronic acidHCID 86658503HCID 86658503, compound

Product 1

HCID 86658502HCID 86658502, compoundYield 66.8%

Reagents, catalysts & solvents 2

HCID 178482903HCID 178482903, compoundCatalystHCID 962WaterSolvent2×

Conditions

Temperature
100 °C

Procedure

To a microwave vessel was added 7-bromo-3-chloro-5′-(methoxymethyl)-5′H-spiro[chromeno[2,3-c]pyridine-5,4′-thiazol]-2′-amine (1.50 g, 3.52 mmol, prepared as described in Method CC27), potassium phosphate (2.24 g, 10.55 mmol), (2-fluoropyridin-3-yl)boronic acid (1.14 g, 8.09 mmol), 1,1-bis[(di-t-butyl-p-dimethylaminophenyl]palladium(ii) chloride (0.25 g, 0.35 mmol), dioxane (13.2 mL), and water (4.4 mL). The resulting mixture was then heated at 100° C. in a microwave for 10 min. The reaction mixture was diluted with water and extracted with EtOAc. The organic extract was washed with brine, dried over MgSO4, filtered and concentrated in vacuo to give the crude material as an 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 (80 g), eluting with a gradient of 30% to 45% to 60% DCM/MeOH/NH4OH (90/10/1) in 40% EtOAc in Heptane, to provide 3-chloro-7-(2-fluoropyridin-3-yl)-5′-(methoxymethyl)-5′H-spiro[chromeno[2,3-c]pyridine-5,4′-thiazol]-2′-amine (1.04 g, 2.35 mmol, 66.8% yield) as off-white solid.

Workup

  1. extractionextracted with EtOAc
  2. extractionThe organic extract
  3. washwas washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give the crude material as an orange solid
  8. customThe crude material was absorbed onto a plug of silica gel
  9. custompurified by chromatography through a gold Redi-Sep pre-packed silica gel column (80 g)
  10. washeluting with a gradient of 30% to 45% to 60% DCM/MeOH/NH4OH (90/10/1) in 40% EtOAc in Heptane

Sources & evidence

ORD record
ord-04c98665e24548f1a16539ae538ed676
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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