1,4-Dioxane → HCID 67383456, compound

HRID 335983Notes

Reaction equation

HRID 335983 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]2[O:8][C:9]3[C:14]([C:15]4([CH:19]([CH2:20][O:21][CH3:22])[S:18][C:17]([NH2:23])=[N:16]4)[C:4]=2[CH:3]=1)=[CH:13][C:12]([C:24]1[C:25]([F:30])=[N:26][CH:27]=[CH:28][CH:29]=1)=[CH:11][CH:10]=3.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:39][C:40]1[CH:45]=[C:44](B(O)O)[CH:43]=[CH:42][N:41]=1.O1CCOCC1>CCOC(C)=O.O.C(C1C(C(C)(C)C)=C([Pd]Cl)C=CC=1N(C)C)(C)(C)C.C(Cl)Cl>[F:30][C:25]1[C:24]([C:12]2[CH:13]=[C:14]3[C@@:15]4([C@@H:19]([CH2:20][O:21][CH3:22])[S:18][C:17]([NH2:23])=[N:16]4)[C:4]4[CH:3]=[C:2]([C:44]5[CH:43]=[CH:42][N:41]=[C:40]([F:39])[CH:45]=5)[N:7]=[CH:6][C:5]=4[O:8][C:9]3=[CH:10][CH:11]=2)=[CH:29][CH:28]=[CH:27][N:26]=1

Participants

9

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 27833962-Fluoropyridine-4-boronic acidHCID 86658502HCID 86658502, compound

Product 1

HCID 67383456HCID 67383456, compoundYield 64.6%

Reagents, catalysts & solvents 4

HCID 178482903HCID 178482903, compoundCatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
135 °C

Procedure

To a vial was added 3-chloro-7-(2-fluoropyridin-3-yl)-5′-(methoxymethyl)-5′H-spiro[chromeno[2,3-c]pyridine-5,4′-thiazol]-2′-amine (715 mg, 1.61 mmol), potassium phosphate (1.20 g, 5.65 mmol), (2-fluoropyridin-4-yl)boronic acid (910 mg, 6.46 mmol), and then dioxane (8.1 mL) and water (2.7 mL) were added. The mixture was purged with N2 and finally 1,1-bis[(di-t-butyl-p-dimethylaminophenyl]palladium(II) chloride (114 mg, 0.16 mmol) was added. The resulting mixture was then heated 135° C. in a microwave for 15 min. The reaction mixture were diluted with EtOAc and water. The organic extract was washed with brine, dried over MgSO4, filtered and concentrated in vacuo to give the crude material as a orange solid. Small amount of DCM was added and light brown precipitate formed. After filtration through Buchner funnel gave (4′S,5′S)-7-(2-fluoropyridin-3-yl)-3-(2-fluoropyridin-4-yl)-5′-(methoxymethyl)-5′H-spiro[chromeno[2,3-c]pyridine-5,4′-thiazol]-2′-amine (523 mg, 1.04 mmol, 64% yield) as light brown solid.

Workup

  1. customThe mixture was purged with N2
  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 a orange solid
  8. customlight brown precipitate formed
  9. filtrationAfter filtration through Buchner funnel

Sources & evidence

ORD record
ord-58228a125ce9418dacbce2dcb46ab9f1
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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