Potassium Phosphate, Tribasic → 2-(2-(4-methoxybenzylamino)-3-(tetrahydro-2H-pyran-4-yl) quinolin-6-yl)-3-methylbenzonitrile

HRID 1029015Notes

Reaction equation

HRID 1029015 reaction equation
Br[C:2]1[C:9]([CH3:10])=[CH:8][CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[CH3:11][O:12][C:13]1[CH:45]=[CH:44][C:16]([CH2:17][NH:18][C:19]2[C:28]([CH:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[CH:27][C:26]3[C:21](=[CH:22][CH:23]=[C:24](B4OC(C)(C)C(C)(C)O4)[CH:25]=3)[N:20]=2)=[CH:15][CH:14]=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]>[CH3:11][O:12][C:13]1[CH:14]=[CH:15][C:16]([CH2:17][NH:18][C:19]2[C:28]([CH:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[CH:27][C:26]3[C:21](=[CH:22][CH:23]=[C:24]([C:2]4[C:9]([CH3:10])=[CH:8][CH:7]=[CH:6][C:3]=4[C:4]#[N:5])[CH:25]=3)[N:20]=2)=[CH:44][CH:45]=1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 154691152-Bromo-3-methylbenzonitrileHCID 21081571Dicyclohexyl(2',4',6'-tripropyl-[1,1'-biphenyl]-2-yl)phosphineHCID 71253356N-(4-methoxybenzyl)-3-(tetrahydro-2H-pyran-4-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine

Product 1

HCID 673256072-(2-(4-methoxybenzylamino)-3-(tetrahydro-2H-pyran-4-yl) quinolin-6-yl)-3-methylbenzonitrile

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
140 °C

Procedure

A mixture of 2-bromo-3-methylbenzonitrile (0.744 g, 3.79 mmol), N-(4-methoxybenzyl)-3-(tetrahydro-2H-pyran-4-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine (0.60 g, 1.265 mmol), 2-(dicyclohexylphosphino)-2′,4′,6′,-tri-1-propyl-1,1′-biphenyl (0.121 g, 0.253 mmol), potassium phosphate, anhydrous (0.524 mL, 6.32 mmol), and Pd2(dba)3 (0.116 g, 0.126 mmol) was purged with N2 followed by the addition of degassed dioxane (2 mL) and degassed water (1.0 mL). The resulting mixture was heated in microwave at 140° C. for 12 min. The reaction went to completion and it was filtered, concentrated, and chromatographed on silica gel using gradient 2:1 hexanes/EtOAc to afford a yellow solid as (2-(2-(4-methoxybenzylamino)-3-(tetrahydro-2H-pyran-4-yl) quinolin-6-yl)-3-methylbenzonitrile.

Workup

  1. customwas purged with N2
  2. additionfollowed by the addition of degassed dioxane (2 mL)
  3. customdegassed water (1.0 mL)
  4. filtrationwas filtered
  5. concentrationconcentrated
  6. customchromatographed on silica gel using gradient 2:1 hexanes/EtOAc

Sources & evidence

ORD record
ord-39d46e396bbf4533a4f470ac98ea578f
Source dataset
uspto-grants-2014_05
Patent number
US08735384B2

Reaction notes

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