Cesium carbonate → 2-Fluro-4-(3-methyl-pyrazol-1-yl)phenylamine

HRID 2217573Notes

Reaction equation

HRID 2217573 reaction equation
[F:1][C:2]1[CH:8]=[C:7](I)[CH:6]=[CH:5][C:3]=1[NH2:4].[CH3:10][C:11]1[CH:15]=[CH:14][NH:13][N:12]=1.C([O-])([O-])=O.[Cs+].[Cs+].N[C@@H]1CCCC[C@H]1N>[Cu]I>[F:1][C:2]1[CH:8]=[C:7]([N:13]2[CH:14]=[CH:15][C:11]([CH3:10])=[N:12]2)[CH:6]=[CH:5][C:3]=1[NH2:4]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 438061,2-Diaminocyclohexane, trans-HCID 1856942-Fluoro-4-iodoanilineHCID 178428694HCID 178428694, compound

Product 1

HCID 221815262-Fluro-4-(3-methyl-pyrazol-1-yl)phenylamineYield 38.1%

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Procedure

2-Fluoro-4-iodoaniline (3.0 g, 12.6 mmol), 3-methylpyrazole (1.22 mL, 15.18 mmol), Cs2CO3 (8.66 g, 26.58 mmol) and CuI (0.072 g, 0.379 mmol) were placed in a flask under nitrogen. The flask was evacuated under vacuum and refilled with nitrogen (5 times). 1,4-Dioxane (15 mL) was added followed by trans-1,2-diaminocyclohexane (152 μL, 1.266 mmol). The reaction mixture was heated under reflux for 36 h. Mixture cooled and filtered. Solvents removed. Residue purified by silica gel flash chromatography eluting with a gradient of EtOAc in hexanes (0 to 30%). This purification afforded 1 as a pale brown solid (0.917 g, 38%). MS: APCI (AP+): 192.0 (M)+.

Workup

  1. customThe flask was evacuated under vacuum
  2. additionrefilled with nitrogen (5 times)
  3. addition1,4-Dioxane (15 mL) was added
  4. temperatureThe reaction mixture was heated
  5. temperatureunder reflux for 36 h
  6. temperatureMixture cooled
  7. filtrationfiltered
  8. customSolvents removed
  9. customResidue purified by silica gel flash chromatography
  10. washeluting with a gradient of EtOAc in hexanes (0 to 30%)
  11. customThis purification

Sources & evidence

ORD record
ord-eafcf545c65f42aeb3217de407a33e78
Source dataset
uspto-grants-2008_08
Patent number
US07407974B2

Reaction notes

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