Diisopropylamine → 5-[3-(3,4-Dihydro-1H-isoquinolin-2-yl)-prop-1-ynyl]-4-(2,2-dimethyl-propylamino)-pyrimidine-2-carbonitrile

HRID 1163013Notes

Reaction equation

HRID 1163013 reaction equation
[CH2:1]([N:4]1[CH2:13][CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5]1)[C:2]#[CH:3].Br[C:15]1[C:16]([NH:23][CH2:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[N:17][C:18]([C:21]#[N:22])=[N:19][CH:20]=1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(NC(C)C)(C)C>O1CCOCC1.[Pd](Cl)Cl.C(#N)C1C=CC=CC=1.C(#N)C1C=CC=CC=1.[Cu]I>[CH2:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH2:12][CH2:13][N:4]1[CH2:1][C:2]#[C:3][C:15]1[C:16]([NH:23][CH2:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[N:17][C:18]([C:21]#[N:22])=[N:19][CH:20]=1

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 143412942-(Prop-2-yn-1-yl)-1,2,3,4-tetrahydroisoquinolineHCID 179681615-Bromo-4-(2,2-dimethylpropylamino)pyrimidine-2-carbonitrile

Product 1

HCID 102478975-[3-(3,4-Dihydro-1H-isoquinolin-2-yl)-prop-1-ynyl]-4-(2,2-dimethyl-propylamino)-pyrimidine-2-carbonitrileYield 46.5%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 498840Bis(benzonitrile)palladium chlorideCatalystHCID 312751,4-DioxaneSolvent

Procedure

2-Prop-2-ynyl-1,2,3,4-tetrahydro-isoquinoline (0.72 mmol), 5-bromo-4-(2,2-dimethyl-propylamino)-pyrimidine-2-carbonitrile (0.86 mmol), Bis(benzonitrile)-palladium(II) chloride (0.02 mmol), copper (I) iodide (0.015 mmol), tri-tert-butylphosphine (0.04 mmol) and diisopropyl amine (0.86 mmol) in dioxane (4 ml) is stirred at room temperature for 2.5 h. After filtration, the reaction mixture is treated with saturated ammonium chloride. The mixture is extracted with AcOEt. The organic layer is washed with brine, dried over magnesium sulfate and evaporated down. The crude product is applied to a column of silica gel, which is eluted with following solvents: n-hexane:AcOEt=1:1 (v/v) and n-hexane:AcOEt=1:5 (v/v). The solvent of the latter effluent is removed by evaporation and dried in vacuo afford the title compound. yield 46.5%, Rf=0.31 (n-hexane:AcOEt=1:1).

Workup

  1. filtrationAfter filtration
  2. additionthe reaction mixture is treated with saturated ammonium chloride
  3. extractionThe mixture is extracted with AcOEt
  4. washThe organic layer is washed with brine
  5. dry with materialdried over magnesium sulfate
  6. customevaporated down
  7. washis eluted with following solvents
  8. customThe solvent of the latter effluent is removed by evaporation
  9. customdried in vacuo

Sources & evidence

ORD record
ord-f63c4afcdfba46c780e0c1191f428b1e
Source dataset
uspto-grants-2010_10
Patent number
US07820818B2

Reaction notes

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