Potassium Iodide → N-ethyl-3-[7-{2-[isopropyl(methyl)amino]ethoxy}-4-methyl-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzamide

HRID 507005Notes

Reaction equation

HRID 507005 reaction equation
Cl[CH2:2][CH2:3][O:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9]([CH3:28])=[CH:10][N:11]([C:16]3[CH:17]=[C:18]([CH:24]=[CH:25][C:26]=3[CH3:27])[C:19]([NH:21][CH2:22][CH3:23])=[O:20])[C:12]2=[O:15])=[CH:7][CH:6]=1.[I-].[K+].[CH3:31][NH:32][CH:33]([CH3:35])[CH3:34]>CC(N(C)C)=O.C(OCC)(=O)C>[CH2:22]([NH:21][C:19](=[O:20])[C:18]1[CH:24]=[CH:25][C:26]([CH3:27])=[C:16]([N:11]2[CH:10]=[C:9]([CH3:28])[C:8]3[C:13](=[CH:14][C:5]([O:4][CH2:3][CH2:2][N:32]([CH:33]([CH3:35])[CH3:34])[CH3:31])=[CH:6][CH:7]=3)[C:12]2=[O:15])[CH:17]=1)[CH3:23]

Participants

6

Reactant 3

HCID 4875Potassium IodideHCID 78485N-MethylisopropylamineHCID 670185833-[7-(2-chloroethoxy)-4-methyl-1-oxoisoquinolin-2(1H)-yl]-N-ethyl-4-methylbenzamide

Product 1

HCID 11690636N-ethyl-3-[7-{2-[isopropyl(methyl)amino]ethoxy}-4-methyl-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzamide

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 3-[7-(2-chloroethoxy)-4-methyl-1-oxoisoquinolin-2(1H)-yl]-N-ethyl-4-methylbenzamide (90 mg), potassium iodide (75 mg), and N-methylisopropylamine (0.14 ml) were stirred in DMA (2 ml) and heated under microwave irradiation conditions (Personal Chemistry Emrys Optimizer with 300 W magnetron) at 150° C. for 1 hour. The reaction mixture was diluted with ethyl acetate and washed with water (×5), brine (×2), dried (magnesium sulfate) and concentrated. Purification by column chromatography on a silica column eluting using initially 10% methanol/ethyl acetate and then a 99:1 mixture of 110% methanol/ethyl acetate and aqueous ammonia solution gave N-ethyl-3-[7-{2-[isopropyl(methyl)amino]ethoxy}-4-methyl-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzamide (68 mg) as a cream solid; NMR Spectrum: (DMSOd6) 0.98 (d, 6H), 1.12 (t, 3H), 2.11 (s, 3H), 2.25 (s, 3H), 2.27 (s, 3H), 2.78 (t, 2H), 2.85 (m, 1H), 3.29 (m, 2H), 4.15 (m, 2H), 7.10 (s, 1H), 7.45-7.51 (m, 2H), 7.70-7.77 (m, 3H), 7.88 (d, 1H), 8.47 (t, 1H); Mass Spectrum: M+H+ 436.

Workup

  1. washwashed with water (×5), brine (×2)
  2. dry with materialdried (magnesium sulfate)
  3. concentrationconcentrated
  4. customPurification by column chromatography on a silica column
  5. washeluting
  6. additiona 99:1 mixture of 110% methanol/ethyl acetate and aqueous ammonia solution

Sources & evidence

ORD record
ord-54498325c60245dcb9783b7a0c1561a9
Source dataset
uspto-grants-2010_08
Patent number
US07786115B2

Reaction notes

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