Acetamide → HCID 89814421, compound

HRID 715102Notes

Reaction equation

HRID 715102 reaction equation
Cl[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:14]3[CH:15]=[CH:16][C:17]([F:21])=[C:18]([CH:20]=3)[NH2:19])[C:8]([CH2:12][CH3:13])=[N:9]2)=[CH:4][N:3]=1.[C:22]([NH2:25])(=[O:24])[CH3:23].[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(P(C(C)(C)C)C1N(C2C(C3C=CC=CC=3)=NN(C3C=CC=CC=3)C=2C2C=CC=CC=2)N=CC=1)(C)C>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]>[NH2:19][C:18]1[CH:20]=[C:14]([C:7]2[C:8]([CH2:12][CH3:13])=[N:9][C:10]3[C:5]([CH:6]=2)=[CH:4][N:3]=[C:2]([NH:25][C:22](=[O:24])[CH3:23])[CH:11]=3)[CH:15]=[CH:16][C:17]=1[F:21]

Participants

7

Reactant 4

HCID 178AcetamideHCID 62657Potassium Phosphate, TribasicHCID 11547931BippyPhosHCID 89815698HCID 89815698, compound

Product 1

HCID 89814421HCID 89814421, compoundYield 37%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

Sparge a solution of 5-(7-chloro-2-ethyl-1,6-naphthyridin-3-yl)-2-fluoroaniline (0.63 g, 2.088 mmol) in dioxane (20 mL) with argon, add acetamide (0.987 g, 16.70 mmol), K3PO4 (1.773 g, 8.35 mmol), Pd2(dba)3 (0.096 g, 0.104 mmol) and BippyPhos (0.106 g, 0.209 mmol) and heat at 80° C. for 16 h. Cool to RT, remove the solids via filtration through diatomaceous earth, rinse well with EtOAc and H2O, and separate the layers of the filtrate. Extract the aqueous layer with EtOAc (1×), wash the combined organics with brine, dry over Na2SO4, concentrate to dryness and purify via silica gel chromatography (EtOAc/Hex) to afford the title compound (250 mg, 37%) as an off-white solid. MS(ESI) m/z: 325.1 (M+H+).

Workup

  1. temperatureCool to RT
  2. customremove the solids
  3. filtrationvia filtration through diatomaceous earth
  4. washrinse well with EtOAc and H2O
  5. customseparate the layers of the filtrate
  6. extractionExtract the aqueous layer with EtOAc (1×)
  7. washwash the combined organics with brine
  8. dry with materialdry over Na2SO4
  9. concentrationconcentrate to dryness
  10. custompurify via silica gel chromatography (EtOAc/Hex)

Sources & evidence

ORD record
ord-720d673567de450e966d1eb22566db36
Source dataset
uspto-grants-2015_11
Patent number
US09187474B2

Reaction notes

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