Cesium carbonate → HCID 90027059, compound

HRID 2200106Notes

Reaction equation

HRID 2200106 reaction equation
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:10]=2[F:18])[CH:5]=[CH:4][N:3]=1.[CH:19]1([C:22]([NH2:24])=[O:23])[CH2:21][CH2:20]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>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].O.O1CCOCC1>[F:18][C:10]1[CH:11]=[C:12]([N+:15]([O-:17])=[O:16])[CH:13]=[CH:14][C:9]=1[NH:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:24][C:22]([CH:19]2[CH2:21][CH2:20]2)=[O:23])[CH:7]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 80376CyclopropanecarboxamideHCID 634876Binap, (A+-)-HCID 90020217HCID 90020217, compound

Product 1

HCID 90027059HCID 90027059, compoundYield 54.2%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Mix 2-chloro-N-(2-fluoro-4-nitro-phenyl)pyridin-4-amine (280 mg, 1.05 mmol), cyclopropanecarboxamide (267 mg, 3.15 mmol), Cs2CO3 (863 mg, 2.63 mmol), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (BINAP, 65 mg, 1.05 mmol), tris(dibenzylideneacetone)dipalladium [Pd2(dba)3, 48 mg, 0.053 mmol] and 1,4-dioxane (6 mL) in a 50 mL round bottom flask, heat at 100° C. under N2 for 16 hrs. Cool the reaction to 25° C., add water (40 mL), extract with EtOAc (10 mL×2). Combine the organic layers; wash with brine (15 mL), dry over anhydrous Na2SO4. Concentrate under reduced pressure to give the crude product. Purification by chromatography (silica gel, PE:EtOAc=7:3) affords the target compound (180 mg, 54%). MS: (M+1): 317.1.

Workup

  1. temperatureCool
  2. customthe reaction to 25° C.
  3. extractionextract with EtOAc (10 mL×2)
  4. washwash with brine (15 mL)
  5. dry with materialdry over anhydrous Na2SO4
  6. concentrationConcentrate under reduced pressure
  7. customto give the crude product
  8. customPurification by chromatography (silica gel, PE:EtOAc=7:3)

Sources & evidence

ORD record
ord-1b91e333e5e54071b75fb50f2115c014
Source dataset
uspto-grants-2016_06
Patent number
US09359338B2

Reaction notes

Loading…