Cesium carbonate → 5-(2,6-Dichloropyrimidin-4-yl)-3-(trifluoromethyl)pyridin-2-amine

HRID 1778172Notes

Reaction equation

HRID 1778172 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[CH:5]=[C:4](Cl)[N:3]=1.CC1(C)C(C)(C)OB([C:18]2[CH:19]=[C:20]([C:25]([F:28])([F:27])[F:26])[C:21]([NH2:24])=[N:22][CH:23]=2)O1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C.O.[Pd](Cl)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:1][C:2]1[N:3]=[C:4]([C:18]2[CH:19]=[C:20]([C:25]([F:28])([F:27])[F:26])[C:21]([NH2:24])=[N:22][CH:23]=2)[CH:5]=[C:6]([Cl:8])[N:7]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 773782,4,6-TrichloropyrimidineHCID 468641035-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)pyridin-2-amine

Product 1

HCID 1176780915-(2,6-Dichloropyrimidin-4-yl)-3-(trifluoromethyl)pyridin-2-amineYield 59.3%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

To a microwave vial charged with 2,4,6-trichloropyrimidine (300 mg, 1.64 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)pyridin-2-amine (518 mg, 1.80 mmol) and cesium carbonate (1.07 g, 3.27 mmol) in acetonitrile/water (4:1, 30 mL) was added 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride (60 mg, 0.05 mmol) under nitrogen. The mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated in vacuo, and resulting residue was purified by flash column chromatography (15% ethyl acetate in petroleum ether to 50% ethyl acetate in petroleum ether) to provide 5-(2,6-dichloropyrimidin-4-yl)-3-(trifluoromethyl)pyridin-2-amine (300 mg, 59.3% yield). LCMS (ESI): [MH]+=308.7.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customresulting residue
  3. customwas purified by flash column chromatography (15% ethyl acetate in petroleum ether to 50% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-164ab84daca64bfd8381e823dc25c02b
Source dataset
uspto-grants-2016_02
Patent number
US09266862B2

Reaction notes

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