Potassium Iodide → N-cyclopropyl-4-methyl-3-[7-[2-(1,4-oxazepan-4-yl)ethoxy]-1-oxoisoquinolin-2(1H)-yl]benzamide

HRID 506964Notes

Reaction equation

HRID 506964 reaction equation
Cl[CH2:2][CH2:3][O:4][C:5]1[CH:14]=[C:13]2[C:8]([CH:9]=[CH:10][N:11]([C:16]3[CH:17]=[C:18]([CH:25]=[CH:26][C:27]=3[CH3:28])[C:19]([NH:21][CH:22]3[CH2:24][CH2:23]3)=[O:20])[C:12]2=[O:15])=[CH:7][CH:6]=1.[I-].[K+].Cl.[O:32]1[CH2:38][CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.CCN(C(C)C)C(C)C>CC(N(C)C)=O.C(OCC)(=O)C>[CH:22]1([NH:21][C:19](=[O:20])[C:18]2[CH:25]=[CH:26][C:27]([CH3:28])=[C:16]([N:11]3[CH:10]=[CH:9][C:8]4[C:13](=[CH:14][C:5]([O:4][CH2:3][CH2:2][N:35]5[CH2:36][CH2:37][CH2:38][O:32][CH2:33][CH2:34]5)=[CH:6][CH:7]=4)[C:12]3=[O:15])[CH:17]=2)[CH2:24][CH2:23]1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 81531DiisopropylethylamineHCID 230902141,4-Oxazepane hydrochlorideHCID 670185703-[7-(2-Chloroethoxy)-1-oxoisoquinolin-2(1H)-yl]-N-cyclopropyl-4-methylbenzamide

Product 1

HCID 11684049N-cyclopropyl-4-methyl-3-[7-[2-(1,4-oxazepan-4-yl)ethoxy]-1-oxoisoquinolin-2(1H)-yl]benzamideYield 65.3%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
150 °C

Procedure

3-[7-(2-Chloroethoxy)-1-oxoisoquinolin-2(1H)-yl]-N-cyclopropyl-4-methylbenzamide (0.15 g), potassium iodide (0.13 g), 1,4-oxazepane hydrochloride (0.34 g), and N,N′-diisopropylethylamine (0.8 ml) were stirred in DMA (3 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 a gradient of ethyl acetate to 15% methanol/ethyl acetate gave N-cyclopropyl-4-methyl-3-[7-[2-(1,4-oxazepan-4-yl)ethoxy]-1-oxoisoquinolin-2(1H)-yl]benzamide (0.114 g) as a white solid; NMR Spectrum: (DMSOd6) 0.56 (m, 2H), 0.69 (m, 2H), 1.80 (m, 2H), 2.10 (s, 3H), 2.76 (m, 4H), 2.85 (m, 1H), 2.92 (t, 2H), 3.61 (m, 2H), 3.66 (t, 2H), 4.19 (m, 2H), 6.72 (d, 1H), 7.21 (d, 1H), 7.41 (d, 1H), 7.49 (d, 1H), 7.69 (s, 1H), 7.71 (d, 1H), 7.74 (s, 1H), 7.88 (d, 1H), 8.43 (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

Sources & evidence

ORD record
ord-96b45840f56f43558b4ad8e9e4927ea3
Source dataset
uspto-grants-2010_08
Patent number
US07786115B2

Reaction notes

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