Propargyl alcohol → 3-(3-((1-(Quinolin-2-YL)azetidin-3-YL)oxy)pyrazin-2-YL)prop-2-YN-1-OL

HRID 454934

Reaction equation

HRID 454934 reaction equation
Cl[C:2]1[C:3]([O:8][CH:9]2[CH2:12][N:11]([C:13]3[CH:22]=[CH:21][C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:14]=3)[CH2:10]2)=[N:4][CH:5]=[CH:6][N:7]=1.C(N(CC)CC)C.[CH2:30]([OH:33])[C:31]#[CH:32]>[Cu]I>[N:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:21]=[CH:22][C:13]=1[N:11]1[CH2:12][CH:9]([O:8][C:3]2[C:2]([C:32]#[C:31][CH2:30][OH:33])=[N:7][CH:6]=[CH:5][N:4]=2)[CH2:10]1

Participants

5

Reactant 3

HCID 7859Propargyl alcoholHCID 8471TriethylamineHCID 585476972-(3-(3-Chloropyrazin-2-yloxy)azetidin-1-yl)quinoline

Product 1

HCID 585476993-(3-((1-(Quinolin-2-YL)azetidin-3-YL)oxy)pyrazin-2-YL)prop-2-YN-1-OLYield 600%

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Conditions

Temperature
110 °C

Procedure

A microwave tube was charged with 2-(3-((3-chloropyrazin-2-yl)oxy)azetidin-1-yl)quinoline (see PREPARATION P2.6; 150 mg, 0.5 mmol), triethylamine (100 mg, 1.0 mmol), CuI (10 mg, 0.05 mmol), Pd (PPh3)2Cl2 (35 mg, 0.05 mmol), prop-2-yn-1-ol (28 mg, 0.05 mmol). After several cycles of vacuum/purge with argon, 2 mL of DMF are added. The reaction mixture is then stirred at 110° C. under microwave for 2 hours. The reaction mixture is poured onto a solution of NaHCO3 and diluted with EtOAc and the layers are separated. The organic extracts were washed with water (10 mL) and brine (10 mL), dried over Na2SO4, and filtered. The filtrate was evaporated in vacuo and the residue was purified by flash column chromatography on silica gel (5% to 30% EtOAc in petroleum ether) to give the title product (99 mg, 0.3 mmol, 61% yield) as white solid. ESI-MS (M+1): 333 calc. for C19H16N4O2 332.

Workup

  1. customAfter several cycles of vacuum/purge with argon, 2 mL of DMF
  2. additionare added
  3. additionThe reaction mixture is poured onto a solution of NaHCO3
  4. additiondiluted with EtOAc
  5. customthe layers are separated
  6. washThe organic extracts were washed with water (10 mL) and brine (10 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customThe filtrate was evaporated in vacuo
  10. customthe residue was purified by flash column chromatography on silica gel (5% to 30% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-bce3d9b9183341fa93009bcbf97a746a
Source dataset
uspto-grants-2013_07
Patent number
US08497265B2

Linked notes

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