Triethylamine → methyl 3-[7-[3-(dimethylamino)prop-1-yn-1-yl]-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzoate

HRID 506993Notes

Reaction equation

HRID 506993 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[N:12]1[CH:21]=[CH:20][C:19]2[C:14](=[CH:15][C:16](OS(C(F)(F)F)(=O)=O)=[CH:17][CH:18]=2)[C:13]1=[O:30].C(N(CC)CC)C.[CH3:38][N:39]([CH3:43])[CH2:40][C:41]#[CH:42].[Li+].[Cl-]>C(#N)C.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>[CH3:38][N:39]([CH3:43])[CH2:40][C:41]#[C:42][C:16]1[CH:15]=[C:14]2[C:19]([CH:20]=[CH:21][N:12]([C:3]3[CH:4]=[C:5]([CH:10]=[CH:11][C:2]=3[CH3:1])[C:6]([O:8][CH3:9])=[O:7])[C:13]2=[O:30])=[CH:18][CH:17]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 81643N,N-Dimethylpropargylamine2×HCID 433294Lithium ChlorideHCID 86620854methyl 4-methyl-3-[1-oxo-7-{[(trifluoromethyl)sulfonyl]oxy} isoquinolin-2(1H)-yl]benzoate

Product 1

HCID 67018594methyl 3-[7-[3-(dimethylamino)prop-1-yn-1-yl]-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzoate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 178418476HCID 178418476, compoundCatalyst2×HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
80 °C

Procedure

A mixture of the methyl 4-methyl-3-[1-oxo-7-{[(trifluoromethyl)sulfonyl]oxy} isoquinolin-2(1H)-yl]benzoate (284 mg), PdCl2(PPh3)2 (13 mg), CuI (6 mg) and triethylamine (449 μl) were stirred in acetonitrile (4.2 ml) for 20 minutes. 1-Dimethylamino-2-propyne (69 μl) in acetonitrile (2.8 mL) was added dropwise and the reaction was stirred at 80° C. for 22 hours. LiCl (81 mg) was added and stirring continued at 80° C. for 1.5 hours. PdCl2(PPh3)2 (13 mg), CuI (6 mg) and 1-dimethylamino-2-propyne (69 μl) was added and stirring continued for a further 22 hours. The reaction mixture was concentrated and the residue was dissolved in ethyl acetate, washed with water (×5), brine, dried (magnesium sulfate), and concentrated to an oil. Purification by column chromatography on a silica column eluting using a gradient of ethyl acetate to 10% methanol/ethyl acetate gave methyl 3-[7-[3-(dimethylamino)prop-1-yn-1-yl]-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzoate as a light brown solid (126 mg); NMR Spectrum: (DMSOd6) 2.15 (s, 3H), 2.27 (s, 6H), 3.52 (s, 2H), 3.86 (s, 3H), 6.79 (d, 1H), 7.43 (d, 1H), 7.60 (d, 1H), 7.79 (m, 2H), 7.87 (s, 1H), 7.99 (d, 1H), 8.23 (s, 1H); Mass Spectrum: M+H+ 375.

Workup

  1. stirringstirring
  2. waitcontinued at 80° C. for 1.5 hours
  3. stirringstirring
  4. waitcontinued for a further 22 hours
  5. concentrationThe reaction mixture was concentrated
  6. dissolutionthe residue was dissolved in ethyl acetate
  7. washwashed with water (×5), brine
  8. dry with materialdried (magnesium sulfate)
  9. concentrationconcentrated to an oil
  10. customPurification by column chromatography on a silica column
  11. washeluting

Sources & evidence

ORD record
ord-649911f157c54591a5eb969c0dc17251
Source dataset
uspto-grants-2010_08
Patent number
US07786115B2

Reaction notes

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