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

HRID 1163014Notes

Reaction equation

HRID 1163014 reaction equation
[CH2:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=2)[CH2:6][CH2:5]1)[C:2]#[CH:3].Br[C:17]1[C:18]([NH:25][CH2:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[N:19][C:20]([C:23]#[N:24])=[N:21][CH:22]=1.C(N(CC)CC)C>CN(C=O)C.O.[Cu]I.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>[CH3:28][C:27]([CH3:30])([CH3:29])[CH2:26][NH:25][C:18]1[C:17]([C:3]#[C:2][CH2:1][N:4]2[CH2:9][CH2:8][N:7]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=3)[CH2:6][CH2:5]2)=[CH:22][N:21]=[C:20]([C:23]#[N:24])[N:19]=1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 106319131-(2-Propynyl)-4-(2-pyridinyl)-piperazineHCID 179681615-Bromo-4-(2,2-dimethylpropylamino)pyrimidine-2-carbonitrile

Product 1

HCID 117410624-(2,2-Dimethyl-propylamino)-5-[3-(4-pyridin-2-yl-piperazin-1-yl)-prop-1-ynyl]-pyrimidine-2-carbonitrileYield 97%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

1-(2-Propynyl)-4-(2-pyridinyl)-piperazine (prepared from 1-(2-pyridinyl)-piperazine and propargyl bromide) (1.5 mmol) is dissolved in DMF at room temperature under nitrogen atmosphere. To the solution, 5-bromo-4-(2,2-dimethyl-propylamino)-pyrimidine-2-carbonitrile (1 mmol), triethylamine (3 mmol), copper(I) iodide (0.1 mmol), and dichlorobis(triphenylphosphine)palladium(II) (0.05 mmol) are added successively. The mixture is heated at 80° C. under nitrogen atmosphere for 3 h. After cooling at room temperature, the mixture is diluted with H2O and extracted with AcOEt. The organic layer is dried over magnesium sulfate and evaporated in vacuo. The residue is purified by silica gel column chromatography (n-hexane:AcOEt=1:5) to give 4-(2,2-dimethyl-propylamino)-5-[3-(4-pyridin-2-yl-piperazin-1-yl)-prop-1-ynyl]-pyrimidine-2-carbonitrile. Yield 97%. Rf=0.30 (n-hexane:AcOEt 1:5). 1H NMR (400 MHz, CDCl3) δ 0.95 (s, 9H), 2.75-2.73 (m, 4H), 3.36 (d, 2H), 3.63-3.60 (m, 4H), 3.69 (s, 2H), 5.78 (brs, 1H), 6.63-6.67 (m, 2H), 7.47-7.52 (m, 1H), 8.19-8.21 (m, 2H).

Workup

  1. temperatureAfter cooling at room temperature
  2. extractionextracted with AcOEt
  3. dry with materialThe organic layer is dried over magnesium sulfate
  4. customevaporated in vacuo
  5. customThe residue is purified by silica gel column chromatography (n-hexane:AcOEt=1:5)

Sources & evidence

ORD record
ord-96fffc12757b4a53b5e1b8c874d8bb45
Source dataset
uspto-grants-2010_10
Patent number
US07820818B2

Reaction notes

Loading…