Potassium Phosphate, Tribasic → 6-(2-([1,2,4]Triazolo[4,3-a]pyridin-3-yl)-6-methylphenyl)-3-morpholinoquinolin-2-amine

HRID 1028975

Reaktionsgleichung

Reaktionsgleichung von HRID 1028975
Br[C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1[N:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]2=[N:11][N:10]=1.[O:18]1[CH2:23][CH2:22][N:21]([C:24]2[C:25]([NH2:43])=[N:26][C:27]3[C:32]([CH:33]=2)=[CH:31][C:30](B2OC(C)(C)C(C)(C)O2)=[CH:29][CH:28]=3)[CH2:20][CH2:19]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(CCC)=CC(CCC)=CC=2CCC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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]>[N:11]1[N:10]=[C:9]([C:3]2[CH:4]=[CH:5][CH:6]=[C:7]([CH3:8])[C:2]=2[C:30]2[CH:31]=[C:32]3[C:27](=[CH:28][CH:29]=2)[N:26]=[C:25]([NH2:43])[C:24]([N:21]2[CH2:20][CH2:19][O:18][CH2:23][CH2:22]2)=[CH:33]3)[N:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=12

Komponenten

6

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 21081571Dicyclohexyl(2',4',6'-tripropyl-[1,1'-biphenyl]-2-yl)phosphineHCID 673249633-(2-Bromo-3-methylphenyl)-[1,2,4]triazolo[4,3-a]pyridineHCID 673479953-Morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine

Produkt 1

HCID 533289966-(2-([1,2,4]Triazolo[4,3-a]pyridin-3-yl)-6-methylphenyl)-3-morpholinoquinolin-2-amine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysator

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

A mixture of 3-(2-bromo-3-methylphenyl)-[1,2,4]triazolo[4,3-a]pyridine (0.32 g, 1.111 mmol), 3-morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine (0.17 g, 0.479 mmol, prepared as in Example 2, Step 1-2), 2-(dicyclohexylphosphino)-2′,4′,6′,-tri-1-propyl-1,1′-biphenyl (0.046 g, 0.096 mmol), potassium phosphate, anhydrous (0.198 mL, 2.393 mmol), and Pd2(dba)3 (0.044 g, 0.048 mmol) was purged with N2 followed by the addition of degassed dioxane (2 mL) and water (1.0 mL). The resulting mixture was heated in microwave at 140° C. for 12 min. The reaction was filtered, concentrated, and the resulting crude material was chromatographed on silica gel using gradient 2:1 hexanes/EtOAc and 0-5% 2M NH3 in MeOH/DCM to afford a light yellow solid. It was repurified by HPLC to afford 6-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-6-methylphenyl)-3-morpholinoquinolin-2-amine as a white solid. MS (ESI, pos. ion) m/z: 437 (M+1).

Aufarbeitung

  1. customwas purged with N2
  2. additionfollowed by the addition of degassed dioxane (2 mL) and water (1.0 mL)
  3. filtrationThe reaction was filtered
  4. concentrationconcentrated
  5. customthe resulting crude material was chromatographed on silica gel using gradient 2:1 hexanes/EtOAc and 0-5% 2M NH3 in MeOH/DCM
  6. customto afford a light yellow solid
  7. customIt was repurified by HPLC

Quellen und Nachweise

ORD-Eintrag
ord-e305a56c6df94473ad2eec06d29f82b6
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08735384B2

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