Sodium Carbonate → 6-methyl-N1-(2-methyl-5-(trifluoromethyl)phenyl)-N5-(3-(pyrimidin-4-yl)pyridin-2-yl)isoquinoline-1,5-diamine

HRID 1668953Notes

Reaction equation

HRID 1668953 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:8]([NH2:12])=[N:7][CH:6]=[CH:5][C:4]=2[C:3]=1[NH:13][C:14]1[C:19]([C:20]2[CH:25]=[CH:24][N:23]=[CH:22][N:21]=2)=[CH:18][CH:17]=[CH:16][N:15]=1.Br[C:27]1[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:30]=[CH:29][C:28]=1[CH3:37].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.CCOC(C)=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]>[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:8]([NH:12][C:29]3[CH:30]=[C:31]([C:33]([F:34])([F:36])[F:35])[CH:32]=[CH:27][C:28]=3[CH3:37])=[N:7][CH:6]=[CH:5][C:4]=2[C:3]=1[NH:13][C:14]1[C:19]([C:20]2[CH:25]=[CH:24][N:23]=[CH:22][N:21]=2)=[CH:18][CH:17]=[CH:16][N:15]=1

Participants

9

Reactant 5

HCID 10340Sodium CarbonateHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27793762-Bromo-1-methyl-4-(trifluoromethyl)benzeneHCID 589422576-methyl-N5-(3-(pyrimidin-4-yl)pyridin-2-yl)isoquinoline-1,5-diamine

Product 1

HCID 673386246-methyl-N1-(2-methyl-5-(trifluoromethyl)phenyl)-N5-(3-(pyrimidin-4-yl)pyridin-2-yl)isoquinoline-1,5-diamine

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

To 6-methyl-N5-(3-(pyrimidin-4-yl)pyridin-2-yl)isoquinoline-1,5-diamine (0.040 g, 0.12 mmol), charged to a 5 mL microwave reaction vessel, 2-bromo-1-methyl-4-(trifluoromethyl)benzene (0.044 g, 0.18 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (0.016 g, 0.027 mmol), cesium carbonate (0.056 g, 0.17 mmol), and tris(dibenzylideneacetone)dipalladium (o) (0.011 g, 0.012 mmol) were added. The reagents were then suspended in dioxane (2.0 mL). The reaction mixture was stirred at 140° C. for 1 hrs. The reaction mixture was cooled and diluted with excess EtOAc, and partioned with aqueous sodium carbonate. The aqueous layer was back extracted 2× EtOAc. The combined organics were washed with brine, dried with magnesium sulfate and concentrated under vacuum. The resulting residue was loaded on to silica and purified by column Chromatography. (ISCO 40.0 g, 0.5-5% MeOH in DCM, 30 min.) to give 6-methyl-N1-(2-methyl-5-(trifluoromethyl)phenyl)-N5-(3-(pyrimidin-4-yl)pyridin-2-yl)isoquinoline-1,5-diamine as a solid after treatment with diethyl ether. MS (M+H)+ 487.

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionThe aqueous layer was back extracted 2× EtOAc
  3. washThe combined organics were washed with brine
  4. dry with materialdried with magnesium sulfate
  5. concentrationconcentrated under vacuum
  6. custompurified by column Chromatography

Sources & evidence

ORD record
ord-e21bcbe71d7e4ef4b37f0b90b19de52a
Source dataset
uspto-grants-2011_08
Patent number
US07989461B2

Reaction notes

Loading…