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

HRID 517966Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 517966
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]

Komponenten

8

Edukt 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

Produkt 1

HCID 672941523-Amino-4-(methylamino)-6-(4-(pyridin-3-ylmethoxy)-3-(trifluoromethyl)phenyl)picolinonitrileAusbeute 53,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

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%).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-9d9d70eba79148b887e8a85c1fc4b6b9
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09115126B2

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