Cesium carbonate → N-[4-(3-fluoro-4-nitro-anilino)-2-pyridyl]cyclopropanecarboxamide

HRID 2200108Notes

Reaction equation

HRID 2200108 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]([C:10]2[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[C:12]([F:19])[CH:11]=2)C)[CH:5]=[CH:4][N:3]=1.[CH:20]1([C:23]([NH2:25])=[O:24])[CH2:22][CH2:21]1.C([O-])([O-])=O.[Cs+].[Cs+].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>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].CCOC(C)=O>[F:19][C:12]1[CH:11]=[C:10]([CH:15]=[CH:14][C:13]=1[N+:16]([O-:18])=[O:17])[NH:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:25][C:23]([CH:20]2[CH2:22][CH2:21]2)=[O:24])[CH:7]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 80376CyclopropanecarboxamideHCID 634876Binap, (A+-)-HCID 900204772-chloro-N-(3-fluoro-4-nitro-phenyl)-N-methyl-pyridin-4-amine

Product 1

HCID 90020584N-[4-(3-fluoro-4-nitro-anilino)-2-pyridyl]cyclopropanecarboxamideYield 74.4%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Add 2-chloro-N-(3-fluoro-4-nitro-phenyl)-N-methyl-pyridin-4-amine (190 mg, 0.68 mmol), cyclopropanecarboxamide (85 mg, 2.03 mmol), Cs2CO3 (440 mg, 1.35 mmol), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (BINAP, 43 mg, 0.05 mmol) and tris(dibenzylideneacetone)dipalladium [Pd2(dba)3, 42 mg, 0.07 mmol] in 1,4-dioxane (6 mL) under N2. Heat the reaction at 125° C. for 16 hrs. TLC (EtOAc:PE=2:1) shows the reaction is complete. Cool to room temperature, filter, and concentrate the filtrate under reduced pressure to give the crude product. Purification by chromatography (silica gel, EtOAc:PE=2:1) affords the target compound (160 mg, 71.7%). MS: (M+1): 331.

Workup

  1. temperatureHeat
  2. customthe reaction at 125° C. for 16 hrs
  3. filtrationfilter
  4. concentrationconcentrate the filtrate under reduced pressure
  5. customto give the crude product
  6. customPurification by chromatography (silica gel, EtOAc:PE=2:1)

Sources & evidence

ORD record
ord-d629941ff8bf4df5b9f6f0419ee2d4f3
Source dataset
uspto-grants-2016_06
Patent number
US09359338B2

Reaction notes

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