Potassium Phosphate, Tribasic → 3-Amino-4-(methylamino)-6-(4-(pyridin-4-ylmethoxy)-3-(trifluoromethyl)phenyl)picolinonitrile

HRID 517969Notes

Reaction equation

HRID 517969 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:22]=[CH:21][C:12]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)=[C:11]([C:23]([F:26])([F:25])[F:24])[CH:10]=2)O1.[NH2:28][C:29]1[C:30]([C:38]#[N:39])=[N:31][C:32](Cl)=[CH:33][C:34]=1[NH:35][CH3:36].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.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]>[NH2:28][C:29]1[C:30]([C:38]#[N:39])=[N:31][C:32]([C:9]2[CH:22]=[CH:21][C:12]([O:13][CH2:14][C:15]3[CH:16]=[CH:17][N:18]=[CH:19][CH:20]=3)=[C:11]([C:23]([F:24])([F:25])[F:26])[CH:10]=2)=[CH:33][C:34]=1[NH:35][CH3:36]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 576575713-Amino-6-chloro-4-methylamino-pyridine-2-carbonitrileHCID 672942684-((4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)phenoxy)methyl)pyridine

Product 1

HCID 672940653-Amino-4-(methylamino)-6-(4-(pyridin-4-ylmethoxy)-3-(trifluoromethyl)phenyl)picolinonitrileYield 29.4%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)phenoxy)methyl)pyridine (1.39 g), 3-amino-6-chloro-4-(methylamino)-picolinonitrile (0.669 g), tris(dibenzylideneacetone)dipalladium (0) (173 mg), tricyclohexylphosphine (127 mg) and potassium phosphate (1.621 g) in 1,4-dioxane (15 ml) and water (7.5 ml) was stirred at 100° C. for 2 h. The reaction mixture was cooled, filtered to remove insoluble precipitate. The precipitate was dried in vacuum oven to give 430 mg light brown solid as 3-amino-4-(methylamino)-6-(4-(pyridin-4-ylmethoxy)-3-(trifluoromethyl)phenyl)picolinonitrile (29%). Filtrate was partitioned between water and ethyl acetate, washed with water, dried over sodium sulfate, filtered and concentrated. Purified by Biotage SNAP cartridge KP-Sil column (25 g, heptane:ethyl acetate=1:0, 1:1, 1:3 to 0:1 then ethyl acetate:methanol=25:1, 20:1 then dichloromethane:methanol=20:1) to give 568 mg of the title compound as a light brown solid (39%).

Workup

  1. temperatureThe reaction mixture was cooled
  2. filtrationfiltered
  3. customto remove insoluble precipitate
  4. customThe precipitate was dried in vacuum oven

Sources & evidence

ORD record
ord-5809c3b2e0fb4056a2e049cd52193bae
Source dataset
uspto-grants-2015_08
Patent number
US09115126B2

Reaction notes

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