4-Chloro-2-nitroaniline → HCID 89924002, compound

HRID 1500898Notes

Reaction equation

HRID 1500898 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[C:4]([N+:9]([O-:11])=[O:10])[CH:3]=1.Br[C:13]1[CH:14]=[CH:15][C:16]([F:19])=[N:17][CH:18]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.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]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:13]2[CH:18]=[N:17][C:16]([F:19])=[CH:15][CH:14]=2)=[C:4]([N+:9]([O-:11])=[O:10])[CH:3]=1

Participants

7

Reactant 4

HCID 69794-Chloro-2-nitroanilineHCID 10796Cesium carbonateHCID 27831685-Bromo-2-fluoropyridineHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl

Product 1

HCID 89924002HCID 89924002, compoundYield 59.8%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

To the solution of 4-chloro-2-nitro-phenylamine (862 mg, 5.0 mmol), 5-bromo-2-fluoro-pyridine (924 mg, 5.25 mmol) in dioxane (15 mL) was added 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (289 mg, 0.5 mmol), Pd2(dba)3 (457.5 mg, 0.5 mmol), followed by cesium carbonate (3.26 g, 10.0 mmol). After degassed and refilled with nitrogen for three times, the reaction mixture in vessel was stirred at 110° C. for overnight till all starting material has been consumed. The reaction mixture was quenched with ice water, the solid was filtered and collected, washed with water, and dried over oven to yield the nitro product about 800 mg as crude solid (yield: 60%). To the solution of (4-chloro-2-nitro-phenyl)-(6-fluoro-pyridin-3-yl)-amine (800 mg, 3.0 mmol) in methanol (10 mL) was added Raney Ni (slurry in water, 100 mg), followed by hydrazine (2 mL), the reaction mixture was stirred at RT for 30 min, till all starting material has gone. The mixture was filtered and the filtrate was combined. After evaporated under reduced pressure, about 600 mg of the residue was obtained as crude product (yield: 90%). The cyclization step is as the same as previous description in Example 2-1. MS obsd. (ESI+) [(M+H)+], 296.

Workup

  1. customAfter degassed
  2. additionrefilled with nitrogen for three times
  3. customhas been consumed
  4. customThe reaction mixture was quenched with ice water
  5. filtrationthe solid was filtered
  6. customcollected
  7. washwashed with water
  8. customdried over oven

Sources & evidence

ORD record
ord-2caa9d3f7f6e4ad9b45ae9f0c90ae8b7
Source dataset
uspto-grants-2015_12
Patent number
US09206191B2

Reaction notes

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