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

HRID 507010Notes

Reaction equation

HRID 507010 reaction equation
Cl[CH2:2][CH2:3][O:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9]([CH3:30])=[CH:10][N:11]([C:16]3[CH:17]=[C:18]([CH:26]=[CH:27][C:28]=3[CH3:29])[C:19]([NH:21][CH:22]3[CH2:25][CH2:24][CH2:23]3)=[O:20])[C:12]2=[O:15])=[CH:7][CH:6]=1.[I-].[K+].[CH3:33][NH:34][CH:35]([CH3:37])[CH3:36]>CC(N(C)C)=O.C(OCC)(=O)C>[CH:22]1([NH:21][C:19](=[O:20])[C:18]2[CH:26]=[CH:27][C:28]([CH3:29])=[C:16]([N:11]3[CH:10]=[C:9]([CH3:30])[C:8]4[C:13](=[CH:14][C:5]([O:4][CH2:3][CH2:2][N:34]([CH:35]([CH3:37])[CH3:36])[CH3:33])=[CH:6][CH:7]=4)[C:12]3=[O:15])[CH:17]=2)[CH2:23][CH2:24][CH2:25]1

Participants

6

Reactant 3

HCID 4875Potassium IodideHCID 78485N-MethylisopropylamineHCID 67018554HCID 67018554, compound

Product 1

HCID 11712334N-cyclobutyl-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-cyclobutyl-4-methylbenzamide (131 mg), potassium iodide (102 mg), and N-methylisopropylamine (0.19 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 10% methanol/ethyl acetate and aqueous ammonia solution gave N-cyclobutyl-3-[7-{2-[isopropyl(methyl)amino]ethoxy}-4-methyl-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzamide (74 mg) as a cream solid; NMR Spectrum: (DMSOd6) 0.98 (d, 6H), 1.68 (m, 2H), 2.06 (m, 2H), 2.11 (s, 3H), 2.21 (m, 2H), 2.25 (s, 3H), 2.28 (s, 3H), 2.77 (t, 2H), 2.84 (m, 1H), 4.15 (m, 2H), 4.43 (m, 1H), 7.09 (s, 1H), 7.45-7.51 (m, 2H), 7.71-7.74 (m, 2H), 7.80 (s, 1H), 7.89 (d, 1H), 8.60 (d, 1H); Mass Spectrum: M+H+ 462.

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 10% methanol/ethyl acetate and aqueous ammonia solution

Sources & evidence

ORD record
ord-2106bd635f93440bbda9aca35b01b09f
Source dataset
uspto-grants-2010_08
Patent number
US07786115B2

Reaction notes

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