Triethylamine → HCID 67104672, compound

HRID 273246Notes

Reaction equation

HRID 273246 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5](I)=[C:6]([NH2:8])[CH:7]=1.[CH2:10]([N:14]1[CH2:18][CH2:17][CH2:16][C@H:15]1[CH3:19])[CH2:11][C:12]#[CH:13].C(N(CC)CC)C>C(#N)C.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>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:13]#[C:12][CH2:11][CH2:10][N:14]2[CH2:18][CH2:17][CH2:16][C@H:15]2[CH3:19])=[C:6]([NH2:8])[CH:7]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 11367023(R)-1-(But-3-yn-1-yl)-2-methylpyrrolidineHCID 138036675-Bromo-2-iodoaniline

Product 1

HCID 67104672HCID 67104672, compoundYield 30%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

A solution of Example 168B (0.2 g, 0.67 mmol), 1-but-3-ynyl-(2R)-2-methyl-pyrrolidine (7.4 mL as a 0.1 M solution in acetonitrile, 0.74 mmol), and triethylamine (10 mL, 72.0 mmol) was degassed with nitrogen for 10 minutes while stirring at r.t. Next, Pd(PPh3)2Cl2 (0.010 g, 0.013 mmol) and CuI (0.003 g, 0.013 mmol) were added and the resulting mixture was degassed for an additional 10 minutes, sealed, and stirred at r.t. for 18 hours. Contents were then concentrated under reduced pressure and the residue was dissolved in 100 mL dichloromethane, washed twice with each: 50 mL sat. NaHCO3, 50 mL water, and 50 mL brine, dried with Na2SO4, and concentrated under reduced pressure. The crude material was purified by column chromatography (100% dichloromethane to 95:5 dichloromethane/methanol) to afford the product in 30% yield as a light yellow oil. 1H NMR (CD3OD, 300 MHz) δ 7.03 (d, J=9 Hz, 1H), 6.88 (d, J=3 Hz, 1H), 6.68 (dd, J=3, 9 Hz, 1H), 3.41-3.20 (m, 2H), 2.79-2.52 (m, 5H), 2.12-2.04 (m, 1H), 1.92-1.82 (m, 2H), 1.56-1.47 (m, 1H), 1.25 (d, J=6 Hz, 3H). MS (ESI) [M+H]+ at 308.

Workup

  1. customthe resulting mixture was degassed for an additional 10 minutes
  2. customsealed
  3. stirringstirred at r.t. for 18 hours
  4. concentrationContents were then concentrated under reduced pressure
  5. dissolutionthe residue was dissolved in 100 mL dichloromethane
  6. washwashed twice with each: 50 mL sat. NaHCO3, 50 mL water, and 50 mL brine
  7. dry with materialdried with Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was purified by column chromatography (100% dichloromethane to 95:5 dichloromethane/methanol)
  10. customto afford the product in 30% yield as a light yellow oil

Sources & evidence

ORD record
ord-e11a2efe9cdb47c186219e8c1b4c5f1b
Source dataset
uspto-grants-2008_11
Patent number
US07456196B2

Reaction notes

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