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 517938Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 517938
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]

Komponenten

7

Edukt 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

Produkt 1

HCID 67294138Tert-butyl 4-(2-(4-(5-amino-6-cyano-4-(methylamino)pyridin-2-yl)-2-(trifluoromethyl)phenoxy)ethyl)-piperidine-1-carboxylateAusbeute 70,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-b2273a447aa34b58bf72e9206af504bb
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09115126B2

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