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 517938노트

반응식

HRID 517938 반응식
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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매

반응 조건

온도
100 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-b2273a447aa34b58bf72e9206af504bb
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09115126B2

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