Triethylamine → 4-(2,2-Dimethyl-propylamino)-5-{3-[4-(4-methyl-piperazin-1-yl)-phenyl]-prop-1-ynyl}-pyrimidine-2-carbonitrile

HRID 1984236Notes

Reaction equation

HRID 1984236 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][C:15]#[CH:16])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.Br[C:18]1[C:19]([NH:26][CH2:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[N:20][C:21]([C:24]#[N:25])=[N:22][CH:23]=1.C(N(CC)CC)C.[Cl-].[NH4+]>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH3:29][C:28]([CH3:31])([CH3:30])[CH2:27][NH:26][C:19]1[C:18]([C:16]#[C:15][CH2:14][C:11]2[CH:12]=[CH:13][C:8]([N:5]3[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]3)=[CH:9][CH:10]=2)=[CH:23][N:22]=[C:21]([C:24]#[N:25])[N:20]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 179681615-Bromo-4-(2,2-dimethylpropylamino)pyrimidine-2-carbonitrileHCID 577141261-Methyl4-(4-prop-2-ynyl-phenyl)-piperazine

Product 1

HCID 444502714-(2,2-Dimethyl-propylamino)-5-{3-[4-(4-methyl-piperazin-1-yl)-phenyl]-prop-1-ynyl}-pyrimidine-2-carbonitrileYield 25%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 1-methyl-4-(4-prop-2-ynyl-phenyl)-piperazine (0.75 mmol) and 5-bromo-4-(2,2-dimethyl-propylamino)-pyrimidine-2-carbonitrile (0.5 mmol) in THF (7 ml), triethylamine (1.5 mmol), dichlorobis(triphenylphosphine)palladium (II) (0.025 mmol) and copper (I) iodide (0.05 mmol) are added. The reaction mixture is heated at 60° C. ca. for 3 h. Saturated aqueous solution of ammonium chloride is added to the reaction mixture and then aqueous layer is extracted with two 50 ml portions of AcOEt. The combined extracts are washed with brine, dried over sodium sulfate and concentrated under vacuum to give crude product which is purified by reverse phase HPLC. Yield: 25%. Rf=0.5 (MeOH:CH2Cl2=5:95)

Workup

  1. extractionaqueous layer is extracted with two 50 ml portions of AcOEt
  2. washThe combined extracts are washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customto give crude product which
  6. customis purified by reverse phase HPLC

Sources & evidence

ORD record
ord-6f7e1074d73f41fa895178e9b5ac46a8
Source dataset
uspto-grants-2009_06
Patent number
US07544688B2

Reaction notes

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