1,4-Dioxane → 1-(2-(2-tert-Butylphenoxy)-5-cyanopyridin-3-yl)-3-(4-tert-butylphenyl)urea

HRID 132606

Reaction equation

HRID 132606 reaction equation
[NH2:1][C:2]1[C:3]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[C:17]([CH3:20])([CH3:19])[CH3:18])=[N:4][CH:5]=[C:6]([CH:9]=1)[C:7]#[N:8].[Cu][C:22]#[N:23].[O:24]1[CH2:29]COCC1>[C-]#N.C([N+](CC)(CC)CC)C.CCOCC.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].C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:17]([C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[O:10][C:3]1[C:2]([NH:1][C:29]([NH:23][C:22]2[CH:14]=[CH:13][C:12]([C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:11][CH:16]=2)=[O:24])=[CH:9][C:6]([C:7]#[N:8])=[CH:5][N:4]=1)([CH3:20])([CH3:19])[CH3:18]

Participants

8

Reactant 3

HCID 312751,4-DioxaneHCID 685300435-Amino-6-(2-tert-butylphenoxy)nicotinonitrileHCID 178418546HCID 178418546, compound

Product 1

HCID 115540381-(2-(2-tert-Butylphenoxy)-5-cyanopyridin-3-yl)-3-(4-tert-butylphenyl)urea

Reagents, catalysts & solvents 4

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 3014735Tetraethylammonium cyanideCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 3283Diethyl EtherSolvent

Conditions

Temperature
105 °C

Procedure

5-Amino-6-(2-tert-butylphenoxy)nicotinonitrile: A mixture of 63c (676 mg, 2.1 mmol), copper (1) cyanide (755 mg, 8.4 mmol), tris(dibenzilideneacetone)dipalladium(0) (77 mg, 0.08 mmol), bis(diphenylphosphino)ferrocene (187 mg, 0.34 mmol) and tetraethylammonium cyanide (330 mg, 2.1 mmol) in dioxane (11 mL) was heated at 105° C. overnight. The mixture was cooled to rt, diluted with ether (50 mL), filtered through Celite® and silica (3 g) and concentrated to give a brown solid (883 mg). The solid was purified by SiO2 chromatography (40 g) to afford 63d (472 mg. 84% yield) as a yellow solid; HPLC purity 95%, 3.37 min (Method A); [M+H]+=268.15; 1H NMR (CDCl3) δ ppm: 1.35 (s, 9 H) 4.26 (s, 2 H) 6.95 (d, J=7.70 Hz, 1 H) 7.15 (s, 1 H) 7.20 (t, J=7.70 Hz, 1 H) 7.25 (t, J=7.42 Hz, 1 H) 7.47 (d, J=7.70 Hz, 1 H) 7.82 (s, 1 H); 13C NMR (CDCl3) δ ppm: 154.22, 151.27, 141.40, 139.75, 131.98, 127.57, 127.03, 125.53, 123.53, 121.69, 117.38, 104.08, 34.60, 30.47.

Workup

  1. temperatureThe mixture was cooled to rt
  2. filtrationfiltered through Celite® and silica (3 g)
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-901db812d251499d9e832bd475385333
Source dataset
uspto-grants-2008_06
Patent number
US07388021B2

Linked notes

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