Triethylamine → N-(3-(1-(2-(7-Methoxyquinolin-4-yloxy)ethyl)-6-oxo-1,6-dihydropyridin-3-yl)prop-2-ynyl)-2-(pyrrolidin-1-yl)acetamide

HRID 1878706Notes

Reaction equation

HRID 1878706 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5](=[O:23])[N:6]([CH2:8][CH2:9][O:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=3)[N:14]=[CH:13][CH:12]=2)[CH:7]=1.C(N(CC)CC)C.[CH2:31]([NH:34][C:35](=[O:42])[CH2:36][N:37]1[CH2:41][CH2:40][CH2:39][CH2:38]1)[C:32]#[CH:33]>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>[CH3:22][O:21][C:17]1[CH:16]=[C:15]2[C:20]([C:11]([O:10][CH2:9][CH2:8][N:6]3[C:5](=[O:23])[CH:4]=[CH:3][C:2]([C:33]#[C:32][CH2:31][NH:34][C:35](=[O:42])[CH2:36][N:37]4[CH2:41][CH2:40][CH2:39][CH2:38]4)=[CH:7]3)=[CH:12][CH:13]=[N:14]2)=[CH:19][CH:18]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 248844955-Bromo-1-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridin-2(1H)-oneHCID 77174863N-(prop-2-ynyl)-2-(pyrrolidin-1-yl)acetamide

Product 1

HCID 25018641N-(3-(1-(2-(7-Methoxyquinolin-4-yloxy)ethyl)-6-oxo-1,6-dihydropyridin-3-yl)prop-2-ynyl)-2-(pyrrolidin-1-yl)acetamideYield 24%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalyst

Procedure

To a 50 mL round bottom flask was charged with the 5-bromo-1-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridin-2(1H)-one (0.136 g, 0.4 mmol), trans-dichlorobis(triphenyl-phosphine)palladium (II) (0.005 g, 0.007 mmol), and copper(I) iodide (0.0002 ml, 0.007 mmol) along with a magnetic stirring bar and degassed and back-filled three times with N2. Triethylamine (0.2 ml, 1 mmol) was introduced into the reaction flask using a syringe under the gaseous mixture atmosphere. Then N-(prop-2-ynyl)-2-(pyrrolidin-1-yl)acetamide (0.06 g, 0.4 mmol) was added to the reaction flask. After refluxing for 16 hours, the solvent was evaporated and the residue was shaken with 20 mL of saturated aqueous sodium bicarbonate solution and 50 mL of EtOAc. The organic layer was washed with 20 mL of brine and then dried over anhydrous sodium sulfate. The organic solution was concentrated in vacuo and the residue was purified by a Prep-HPLC to give a yellow solid (0.04 g, 24% yield). MS (ESI pos. ion) m/z (MH+): 461.1. Calc'd Exact Mass for C26H28N4O4: 460.21.

Workup

  1. customdegassed
  2. additionback-filled three times with N2
  3. temperatureAfter refluxing for 16 hours
  4. customthe solvent was evaporated
  5. washThe organic layer was washed with 20 mL of brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationThe organic solution was concentrated in vacuo
  8. customthe residue was purified by a Prep-HPLC

Sources & evidence

ORD record
ord-0e08d5e5e39844f0a1a6a7a67f3d3e97
Source dataset
uspto-grants-2012_11
Patent number
US08314087B2

Reaction notes

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