Cesium carbonate → tert-butyl N-[4-[[2-(cyclopropanecarbonylamino)-4-pyridyl]oxy]-2-fluoro-phenyl]carbamate

HRID 2200116Notes

Reaction equation

HRID 2200116 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[C:11]([F:23])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.[CH:24]1([C:27]([NH2:29])=[O:28])[CH2:26][CH2:25]1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.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]>[CH:24]1([C:27]([NH:29][C:2]2[CH:7]=[C:6]([O:8][C:9]3[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[C:11]([F:23])[CH:10]=3)[CH:5]=[CH:4][N:3]=2)=[O:28])[CH2:26][CH2:25]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 80376CyclopropanecarboxamideHCID 634876Binap, (A+-)-HCID 118223438HCID 118223438, compound

Product 1

HCID 90019939tert-butyl N-[4-[[2-(cyclopropanecarbonylamino)-4-pyridyl]oxy]-2-fluoro-phenyl]carbamateYield 213.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 312751,4-DioxaneSolvent

Procedure

Dissolve tert-butyl N-[4-[(2-chloro-4-pyridyl)oxy]-2-fluoro-phenyl]carbamate (13 g, 14.7 mmol), cyclopropanecarboxamide (8.1 g, 36.7 mmol) in 1,4-dioxane (240 mL). Then add tris(dibenzylideneacetone)dipalladium(0) [Pd2(dba)3, 1.75 g, 0.73 mmol), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (BINAP, 2.38 g, 1.47 mmol) and Cs2CO3 (24.8 g, 29.4 mmol) under N2. Stir the reaction at 100° C. for 12 hrs. Cool to room temperature, filter, and concentrate the filtrate to give the crude product. Purification by chromatography (silica gel, DCM:EtOAc-1:5) affords the title compound (12.14 g, 83.2%). MS: (M+1): 388.

Workup

  1. customthe reaction at 100° C. for 12 hrs
  2. filtrationfilter
  3. concentrationconcentrate the filtrate
  4. customto give the crude product
  5. customPurification by chromatography (silica gel, DCM:EtOAc-1:5)

Sources & evidence

ORD record
ord-d429e7d2c4dc4b52b7dd67ea5e5a7f4f
Source dataset
uspto-grants-2016_06
Patent number
US09359338B2

Reaction notes

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