Cesium carbonate → HCID 86704416, compound

HRID 1748223Notes

Reaction equation

HRID 1748223 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1.[CH:16]12[NH:23][CH:20]([CH2:21][CH2:22]1)[CH2:19][CH:18]([O:24][CH2:25][C:26]1[C:27]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[O:40][C:41]([F:44])([F:43])[F:42])=[N:28][O:29][C:30]=1[CH:31]1[CH2:33][CH2:32]1)[CH2:17]2.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[CH:31]1([C:30]2[O:29][N:28]=[C:27]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[O:40][C:41]([F:42])([F:43])[F:44])[C:26]=2[CH2:25][O:24][CH:18]2[CH2:17][CH:16]3[N:23]([C:2]4[CH:7]=[CH:6][N:5]5[C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:9][N:10]=[C:4]5[CH:3]=4)[CH:20]([CH2:21][CH2:22]3)[CH2:19]2)[CH2:32][CH2:33]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 67260906Ethyl 7-bromoimidazo[1,2-a]pyridine-3-carboxylateHCID 67983256HCID 67983256, compound

Product 1

HCID 86704416HCID 86704416, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A sealable vessel was charged with ethyl 7-bromoimidazo[1,2-a]pyridine-3-carboxylate (67 mg, 0.25 mmol), 4-((8-azabicyclo[3.2.1]octan-3-yloxy)methyl)-5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazole (I-1H) cesium carbonate (122 mg, 0.38 mmol), 1,4-dioxane (2 mL). The mixture was degassed (argon bubble, 10 min) and then tris(dibenzylideneacetone)dipalladium(0) (11 mg, 0.012 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (14 mg, 0.025 mmol) were added. The reaction flask was evacuated and backfilled with Ar three successive times, and then heated to 120° C. for 12 hours. The reaction mixture was cooled to RT, diluted with ethyl acetate (8 mL) and filtered through a CELITE® pad, the filtrate was washed with water (7 mL), dried over magnesium sulfate, concentrated, and chromatographed on silica using linear gradient, 0-100%, EtOAc in Hexanes) to give the desired product as a waxy solid.

Workup

  1. customThe mixture was degassed
  2. custom(argon bubble, 10 min)
  3. customThe reaction flask was evacuated
  4. temperatureThe reaction mixture was cooled to RT
  5. additiondiluted with ethyl acetate (8 mL)
  6. filtrationfiltered through a CELITE® pad
  7. washthe filtrate was washed with water (7 mL)
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated
  10. customchromatographed on silica using linear gradient, 0-100%, EtOAc in Hexanes)

Sources & evidence

ORD record
ord-2fdc9b0b3ab0485db865304d8a101b2d
Source dataset
uspto-grants-2015_10
Patent number
US09150568B2

Reaction notes

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