Triethylamine → 5-Bromo-2-[4-((2r)-2-methyl-pyrrolidin-1-yl)-but-1-ynyl]-phenylamine

HRID 860897Notes

Reaction equation

HRID 860897 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 671046725-Bromo-2-[4-((2r)-2-methyl-pyrrolidin-1-yl)-but-1-ynyl]-phenylamineYield 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
  2. custom10 minutes, sealed
  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-185c5d4f872c4ea0b8a94b84552c4eaa
Source dataset
uspto-grants-2006_12
Patent number
US07153889B2

Reaction notes

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