Diisopropylamine → 4-Bromo-2-[4-(2-(R)-methyl-pyrrolidin-1-yl)-but-1-ynyl]-phenylamine

HRID 900200

Reaction equation

HRID 900200 reaction equation
C#CC(N1CCCC1C)C.[CH2:11]([N:15]1[CH2:19][CH2:18][CH2:17][C@H:16]1[CH3:20])[CH2:12][C:13]#[CH:14].[Br:21][C:22]1[CH:27]=[CH:26][C:25]([NH2:28])=[C:24](I)[CH:23]=1.C(NC(C)C)(C)C>[Cu]I.BrC1C=CC2SC(CCO)=NC=2C=1>[Br:21][C:22]1[CH:27]=[CH:26][C:25]([NH2:28])=[C:24]([C:14]#[C:13][CH2:12][CH2:11][N:15]2[CH2:19][CH2:18][CH2:17][C@H:16]2[CH3:20])[CH:23]=1

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 8239344-Bromo-2-iodoaniline2×HCID 11367023(R)-1-(But-3-yn-1-yl)-2-methylpyrrolidineHCID 219800621-Butyn-3-yl-2-methyl-pyrrolidine

Product 1

HCID 210414944-Bromo-2-[4-(2-(R)-methyl-pyrrolidin-1-yl)-but-1-ynyl]-phenylamineYield 97.3%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 219800605-Bromo-2-benzothiazoleethanolCatalyst

Procedure

To a solution of 1-butyn-3-yl-2-methyl-pyrrolidine in CH3CN (prepared in Example 65A assuming 100% conversion, 89 mmol) was added 4-bromo-2-iodo-phenylamine (12.0 g, 40 mmol) under nitrogen followed by addition of CuI (0.38 g, 2.0 mmol), PdCl2(PPh3) 2 (0.70 mg, 1.0 mmol) and diisopropylamine (33.6 mL, 240 mmol). The resulting solution was stirred at room temperature for 2 hours, at which time analytical HPLC analysis indicated that all 4-bromo-2-iodo-phenylamine was consumed. The solvent CH3CN was removed under vacuo and the residue was extracted with IPAC (500 mL) and 5% NaHCO3 (2×300 mL). The organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure to give the title compound as a thick oil (11.96 g), which was used in the next step without further purification.

Workup

  1. customwas consumed
  2. customThe solvent CH3CN was removed under vacuo
  3. extractionthe residue was extracted with IPAC (500 mL) and 5% NaHCO3 (2×300 mL)
  4. washThe organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-fe5e8f14e298489ba91df93326721103
Source dataset
uspto-grants-2008_04
Patent number
US07358263B2

Linked notes

Loading…