Propargyl alcohol → HCID 118566560, compound

HRID 1056675Notes

Reaction equation

HRID 1056675 reaction equation
[F:1][C:2]1([F:24])[CH2:7][CH2:6][CH:5]([CH2:8][NH:9][C:10]([C:12]2[C:13]3[CH:14]=[CH:15][C:16](Cl)=[N:17][C:18]=3[CH:19]=[CH:20][C:21]=2[Cl:22])=[O:11])[CH2:4][CH2:3]1.[CH2:25]([OH:28])[C:26]#[CH:27]>O1CCOCC1.ClCCl.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[F:1][C:2]1([F:24])[CH2:7][CH2:6][CH:5]([CH2:8][NH:9][C:10]([C:12]2[C:13]3[CH:14]=[CH:15][C:16]([C:27]#[C:26][CH2:25][OH:28])=[N:17][C:18]=3[CH:19]=[CH:20][C:21]=2[Cl:22])=[O:11])[CH2:4][CH2:3]1

Participants

7

Reactant 2

HCID 7859Propargyl alcoholHCID 1185559652,6-Dichloro-quinoline-5-carboxylic acid (4,4-difluorocyclohexylmethyl)-amide

Product 1

HCID 118566560HCID 118566560, compoundYield 75.8%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178419050HCID 178419050, compoundCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 2,6-dichloro-quinoline-5-carboxylic acid (4,4-difluoro-cyclohexylmethyl)-amide (500 mg, 1.24 mmol, 1.00 eq) in degassed 1,4-dioxane (2.50 mL, 5.00 V), prop-2-yn-1-ol (0.09 mL, 1.49 mmol, 1.20 eq) Et3N (0.52 mL, 3.71 mmol, 3.00 eq), Bis(triphenylphosphine)palladium (II) dichloride (34.86 mg, 0.05 mmol, 0.04 eq) and copper (I) iodide (4.81 mg, 0.02 mmol, 0.02 eq) were added. The reaction mixture was heated at 90° C. for 1 h. The reaction mixture was diluted with dichloromethane and filtered through celite. The filtrate was concentrated and subjected to column chromatography to afford the title compound (0.38 g, 0.94 mmol, 75.7%) as a off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 8.87 (t, J=5.92 Hz, 1H), 8.09 (d, J=8.61 Hz, 1H), 8.01 (d, J=9.01 Hz, 1H), 7.86 (d, J=9.11 Hz, 1H), 7.68 (d, J=8.72 Hz, 1H), 5.53 (t, J=6.13 Hz, 1H), 4.39 (d, J=6.01 Hz, 2H), 3.27 (t, J=6.32 Hz, 2H), 1.98-2.04 (m, 2H), 1.74-1.86 (m, 5H), 1.24-1.33 (m, 2H). m/z: 393.2 [M+H]+

Workup

  1. filtrationfiltered through celite
  2. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-04fba834ed44412c94c1e87c8eb4d0c7
Source dataset
uspto-grants-2016_07
Patent number
US09399623B2

Reaction notes

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