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

HRID 2390420노트

반응식

HRID 2390420 반응식
[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

참가 물질

7

반응물 3

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

생성물 1

HCID 671046725-Bromo-2-[4-((2r)-2-methyl-pyrrolidin-1-yl)-but-1-ynyl]-phenylamine수율 30%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418476HCID 178418476, 화합물촉매HCID 6342Acetonitrile용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-4e3de180c142455a956b456bb3cfe0aa
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08273767B2

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