4-Chloro-2-fluoro-1-iodobenzene → 4-(4-chloro-2-fluorophenyl)-5-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-4-amine

HRID 406582Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:13]([CH3:14])[N:12]=[C:11]([CH3:15])[C:10]=1[NH2:16].[Cl:17][C:18]1[CH:23]=[CH:22][C:21](I)=[C:20]([F:25])[CH:19]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([C:10]2([NH2:16])[CH:9]([C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[Cl:1])[N:13]([CH3:14])[N:12]=[C:11]2[CH3:15])=[C:20]([F:25])[CH:19]=1

Participants

Conditions

Temperature: 180 °C

Procedure

A mixture of 5-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-4-amine (i.e. the product of Step F) (7.07 g, 23.8 mmol), 4-chloro-2-fluoroiodobenzene (256 μL, 2.0 mmol), sodium tert-butoxide (0.192 g, 2.0 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (0.117 g, 0.16 mmol) in toluene (5 mL) was heated at 180° C. in a Biotage Initiator™ microwave apparatus for 1 h. The resulting material was purified by flash chromatography on a silica gel (40 g), Varian Bond Elute SI® column (30% ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a dark purple/brown oil (164 mg).

Workup

customThe resulting material was purified by flash chromatography on a silica gel (40 g), Varian Bond
washElute SI® column (30% ethyl acetate in hexanes as eluant)

Sources & evidence

ORD record: ord-4f4b4fe34906469e98d3f9a0ed9ec652
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754115B2

Reaction notes

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