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

HRID 506998Notes

Reaction equation

HRID 506998 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.[N:38]1([CH2:44][C:45]#[CH:46])[CH2:43]COC[CH2:39]1>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>[CH3:39][N:38]([CH3:43])[CH2:44][CH2:45][CH2:46][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

7

Reactant 3

HCID 8471TriethylamineHCID 4129414-(2-Propyn-1-yl)morpholineHCID 86620854methyl 4-methyl-3-[1-oxo-7-{[(trifluoromethyl)sulfonyl]oxy} isoquinolin-2(1H)-yl]benzoate

Product 1

HCID 67018581methyl 3-[7-[3-(dimethylamino)propyl]-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzoateYield 86.9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 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 (400 mg), PdCl2(PPh3)2 (16 mg), CuI (9 mg) and triethylamine (632 μl) were stirred in acetonitrile (10 ml) for 10 minutes. 3-(4-morpholinyl)-1-propyne (114 mg) in acetonitrile (4 ml) was then added dropwise and the reaction was heated at 80° C. for 18 hours and then concentrated. The residue was dissolved in ethyl acetate, washed with water (×3), brine, dried (magnesium sulfate) and concentrated to a brown oil. The oil was purified by column chromatography on an ion exchange column (isolute SCX column from International Sorbent Technology Limited, Henoed, Mid-Glamorgan, UK) using initially methanol and then a 99:1 mixture of methanol and aqueous ammonia solution to yield methyl 3-[7-[3-(dimethylamino)propyl]-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzoate as a brown oil (298 mg); NMR Spectrum: (DMSOd6) 2.15 (s, 3H), 2.55 (m, 4H), 3.57 (s, 2H), 3.63 (m, 4H), 3.87 (s, 3H), 6.78 (d, 1H), 7.42 (d, 1H), 7.60 (d, 1H), 7.79 (m, 2H), 7.86 (s, 1H), 7.99 (d, 1H), 8.24 (s, 1H); Mass Spectrum: M+H+ 417.

Workup

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in ethyl acetate
  3. washwashed with water (×3), brine
  4. dry with materialdried (magnesium sulfate)
  5. concentrationconcentrated to a brown oil
  6. customThe oil was purified by column chromatography on an ion exchange column (isolute SCX column from International Sorbent Technology Limited, Henoed, Mid-Glamorgan, UK)
  7. additiona 99:1 mixture of methanol and aqueous ammonia solution

Sources & evidence

ORD record
ord-261d6122cf1f4d6893f2e00ab9170a58
Source dataset
uspto-grants-2010_08
Patent number
US07786115B2

Reaction notes

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