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

HRID 517966ノート

反応式

HRID 517966 の反応式
CC1(C)C(C)(C)OB([C:9]2[CH:22]=[CH:21][C:12]([O:13][CH2:14][C:15]3[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=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]=[N:17][CH: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]

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 576575713-Amino-6-chloro-4-methylamino-pyridine-2-carbonitrileHCID 672942533-((4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)phenoxy)methyl)pyridine

生成物 1

HCID 672941523-Amino-4-(methylamino)-6-(4-(pyridin-3-ylmethoxy)-3-(trifluoromethyl)phenyl)picolinonitrile収率 53.3%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A suspension of 3-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)phenoxy)methyl)pyridine (2.38 g), 3-amino-6-chloro-4-(methylamino)-picolinonitrile (1.15 g), tris(dibenzylideneacetone)dipalladium (0) (296 mg), tricyclohexylphosphine (218 mg) and potassium phosphate (2.78 g) in 1,4-dioxane (20 ml) and water (10 ml) was stirred at 100° C. for 2 h. The reaction mixture was cooled and partitioned between water and ethyl acetate, washed with water, brine, dried over sodium sulfate, filtered and concentrated. Purified by Biotage SNAP cartridge KP-Sil column (50 g, heptane:ethyl acetate=1:0, 1:1 to 0:1 then dichloromethane:methanol=1:0, 20:1) to give 1.335 g brown solid as 3-amino-4-(methylamino)-6-(4-(pyridin-3-ylmethoxy)-3-(trifluoromethyl)phenyl)picolinonitrile (53%).

後処理

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned between water and ethyl acetate
  3. washwashed with water, brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurified by Biotage SNAP cartridge KP-Sil column (50 g, heptane

出典と根拠

ORDレコード
ord-9d9d70eba79148b887e8a85c1fc4b6b9
出典データセット
uspto-grants-2015_08
特許番号
US09115126B2

反応ノート

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