Triethylamine → (S)-(2,4-dichlorobenzyl)-[1-(5-trimethylsilanylethynylpyrimidin-2-yl)-pyrrolidin-3-yl]-amine

HRID 252138Notes

Reaction equation

HRID 252138 reaction equation
[Cl:1][C:2]1[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:3]=1[CH2:4][NH:5][C@H:6]1[CH2:10][CH2:9][N:8]([C:11]2[N:16]=[CH:15][C:14](Br)=[CH:13][N:12]=2)[CH2:7]1.[CH3:23][Si:24]([C:27]#[CH:28])([CH3:26])[CH3:25].C(N(CC)CC)C>O.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>[Cl:1][C:2]1[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:3]=1[CH2:4][NH:5][C@H:6]1[CH2:10][CH2:9][N:8]([C:11]2[N:16]=[CH:15][C:14]([C:28]#[C:27][Si:24]([CH3:26])([CH3:25])[CH3:23])=[CH:13][N:12]=2)[CH2:7]1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 11503055(3S)-1-(5-bromopyrimidin-2-yl)-N-[(2,4-dichlorophenyl)methyl]pyrrolidin-3-amine

Product 1

HCID 66854856(S)-(2,4-dichlorobenzyl)-[1-(5-trimethylsilanylethynylpyrimidin-2-yl)-pyrrolidin-3-yl]-amineYield 80%

Reagents, catalysts & solvents 3

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

Procedure

In a sealed vessel, heat a mixture of (S)-(2,4-dichlorobenzyl)-[1-(5-bromopyrimidin-2-yl)-pyrrolidin-3-yl]-amine (404 mg, 1.01 mmol), (trimethylsilyl)acetylene (250 μL, 1.76 mmol), dichlorobis(triphenylphosphine)palladium (II) (71.4 mg, 0.10 mmol), copper(I) iodide (20.7 mg, 0.11 mmol) and triethylamine (3 mL) at 100° C. for 4 hours. Cool to room temperature and dilute with water (30 mL). Filter through a pad of Celite®, washing with ethyl acetate. Extract the aqueous with additional ethyl acetate (3×50 mL) and wash the combined organics with saturated aqueous sodium chloride (50 mL). Concentrate and dissolve the residue in dichloromethane, filter, and concentrate to give a residue. Chromatograph the residue on silica gel to give (S)-(2,4-dichlorobenzyl)-[1-(5-trimethylsilanylethynylpyrimidin-2-yl)-pyrrolidin-3-yl]-amine as a yellow oil (337 mg, 80%).

Workup

  1. temperatureIn a sealed vessel, heat
  2. filtrationFilter through a pad of Celite®
  3. washwashing with ethyl acetate
  4. extractionExtract the aqueous with additional ethyl acetate (3×50 mL)
  5. washwash the combined organics with saturated aqueous sodium chloride (50 mL)
  6. concentrationConcentrate
  7. dissolutiondissolve the residue in dichloromethane
  8. filtrationfilter
  9. concentrationconcentrate
  10. customto give a residue

Sources & evidence

ORD record
ord-a53fbd786f6b4f458302799a1c8771f6
Source dataset
uspto-grants-2011_01
Patent number
US07868014B2

Reaction notes

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