1,4-Dioxane → Tert-butyl 4-(2-(4-(5-amino-6-cyano-4-(methylamino)pyridin-2-yl)-2-(trifluoromethyl)phenoxy)ethyl)-piperidine-1-carboxylate

HRID 517938ノート

反応式

HRID 517938 の反応式
CC1(C)C(C)(C)OB([C:9]2[CH:30]=[CH:29][C:12]([O:13][CH2:14][CH2:15][CH:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]3)=[C:11]([C:31]([F:34])([F:33])[F:32])[CH:10]=2)O1.[NH2:36][C:37]1[C:38]([C:46]#[N:47])=[N:39][C:40](Cl)=[CH:41][C:42]=1[NH:43][CH3:44].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.O1CCOCC1>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].O>[NH2:36][C:37]1[C:42]([NH:43][CH3:44])=[CH:41][C:40]([C:9]2[CH:30]=[CH:29][C:12]([O:13][CH2:14][CH2:15][CH:16]3[CH2:17][CH2:18][N:19]([C:22]([O:24][C:25]([CH3:26])([CH3:28])[CH3:27])=[O:23])[CH2:20][CH2:21]3)=[C:11]([C:31]([F:32])([F:33])[F:34])[CH:10]=2)=[N:39][C:38]=1[C:46]#[N:47]

参加物

7

反応物 4

HCID 312751,4-DioxaneHCID 75806TricyclohexylphosphineHCID 576575713-Amino-6-chloro-4-methylamino-pyridine-2-carbonitrileHCID 67294312Tert-butyl 4-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)phenoxy)ethyl)piperidine-1-carboxylate

生成物 1

HCID 67294138Tert-butyl 4-(2-(4-(5-amino-6-cyano-4-(methylamino)pyridin-2-yl)-2-(trifluoromethyl)phenoxy)ethyl)-piperidine-1-carboxylate収率 70.3%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒

反応条件

温度
100 °C

実験手順

The mixture of tert-butyl 4-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)phenoxy)ethyl)piperidine-1-carboxylate (2.41 g), 3-amino-6-chloro-4-(methylamino)picolinonitrile (0.8 g), tris(dibenzylideneacetone)dipalladium (201 mg), tricyclohexylphosphine (147 mg) in a mixed solvent of dioxane (30 ml) and water (15 ml) was heated under nitrogen at 100° C. for 3 hours. After cooling to room temperature, the mixture extracted with ethyl acetate (200 ml), organic layer dried over sodium sulphate, solvent removed under reduced pressure, residue was columned on silica gel using 20:1 DCM:MeOH as eluant to give tert-butyl 4-(2-(4-(5-amino-6-cyano-4-(methylamino)pyridin-2-yl)-2-(trifluoromethyl)phenoxy)ethyl)-piperidine-1-carboxylate (1.6 g) as a brown solid.

後処理

  1. temperatureAfter cooling to room temperature
  2. extractionthe mixture extracted with ethyl acetate (200 ml), organic layer
  3. dry with materialdried over sodium sulphate, solvent
  4. customremoved under reduced pressure, residue

出典と根拠

ORDレコード
ord-b2273a447aa34b58bf72e9206af504bb
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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