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

HRID 1028975Notes

Reaction equation

HRID 1028975 reaction equation
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

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
140 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-e305a56c6df94473ad2eec06d29f82b6
Source dataset
uspto-grants-2014_05
Patent number
US08735384B2

Reaction notes

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