Triethylamine → Ethyl 1-(4-fluorophenyl)-4-oxo-6-((2-(trifluoromethyl)pyridin-4-yl)ethynyl)-1,4-dihydroquinoline-3-carboxylate

HRID 1048886Notes

Reaction equation

HRID 1048886 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)[CH:8]=[C:7]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:6]2=[O:25])#[CH:2].Br[C:27]1[CH:32]=[CH:31][N:30]=[C:29]([C:33]([F:36])([F:35])[F:34])[CH:28]=1.C(N(CC)CC)C>[Cu]I.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.CN(C=O)C>[F:19][C:16]1[CH:17]=[CH:18][C:13]([N:9]2[C:10]3[C:5](=[CH:4][C:3]([C:1]#[C:2][C:27]4[CH:32]=[CH:31][N:30]=[C:29]([C:33]([F:36])([F:35])[F:34])[CH:28]=4)=[CH:12][CH:11]=3)[C:6](=[O:25])[C:7]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:8]2)=[CH:14][CH:15]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 234369504-Bromo-2-(trifluoromethyl)pyridineHCID 121447848Ethyl 6-ethynyl-1-(4-fluorophenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate

Product 1

HCID 121447893Ethyl 1-(4-fluorophenyl)-4-oxo-6-((2-(trifluoromethyl)pyridin-4-yl)ethynyl)-1,4-dihydroquinoline-3-carboxylateYield 45.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

Compound R (20 mg, 0.06 mmol), 4-bromo-2-(trifluoromethyl)pyridine (16.2 mg, 0.07 mmol), CuI (1.1 mg, 0.006 mmol), triethylamine (25 μL, 0.18 mmol), PdCl2(PPh3)2 (2.7 mg, 0.003 mmol), and DMF (600 μL) were added to a small microwave vial. The vial was capped and placed in microwave reactor at 150° C. for fifteen minutes. The reaction was filtered over Celite®, washed very well with a 5% MeOH in DCM solution and concentrated to dryness. Purification by reverse phase HPLC afforded 13 mg (45%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 8.84 (d, J=4.96 Hz, 1H), 8.52-8.5 (m, 2H), 8.17 (s, 1H), 7.93 (d, J=5.04 Hz, 1H), 7.87 (dd, J=8.8 Hz, 1H), 7.81-7.77 (m, 2H), 7.55 (t, J=8.64, 8.68 Hz, 2H), 7.07 (d, J=8.8 Hz, 1H), 4.24 (q, J=7.04, 7.08 Hz, 2H), 1.28 (t, J=7.12, 7.08 Hz, 3H); ES-MS [M+1]+: 481.2.

Workup

  1. customThe vial was capped
  2. waitplaced in microwave reactor at 150° C. for fifteen minutes
  3. filtrationThe reaction was filtered over Celite®
  4. washwashed very well with a 5% MeOH in DCM solution
  5. concentrationconcentrated to dryness
  6. customPurification by reverse phase HPLC

Sources & evidence

ORD record
ord-16aaf134b43640af8765a0f7785cd921
Source dataset
uspto-grants-2016_07
Patent number
US09382208B1

Reaction notes

Loading…