Sodium Iodide → N-cyclopropyl-3-[7-[2-(dimethylamino)ethoxy]-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzamide

HRID 506959Notes

Reaction equation

HRID 506959 reaction equation
[CH:1]1([NH:4][C:5](=[O:25])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([N:13]3[CH:22]=[CH:21][C:20]4[C:15](=[CH:16][C:17]([OH:23])=[CH:18][CH:19]=4)[C:14]3=[O:24])[CH:7]=2)[CH2:3][CH2:2]1.Cl.[CH3:27][N:28]([CH3:32])[CH2:29][CH2:30]Cl.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>CC(C)=O>[CH:1]1([NH:4][C:5](=[O:25])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([N:13]3[CH:22]=[CH:21][C:20]4[C:15](=[CH:16][C:17]([O:23][CH2:30][CH2:29][N:28]([CH3:32])[CH3:27])=[CH:18][CH:19]=4)[C:14]3=[O:24])[CH:7]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 11515516N-Cyclopropyl-3-(7-hydroxy-1-oxoisoquinolin-2(1H)-yl)-4-methylbenzamideHCID 11636816N,N-Dimethylaminoethyl chloride hydrochloride

Product 1

HCID 11668591N-cyclopropyl-3-[7-[2-(dimethylamino)ethoxy]-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzamideYield 70.6%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

N-Cyclopropyl-3-(7-hydroxy-1-oxoisoquinolin-2(1H)-yl)-4-methylbenzamide (0.16 g), 2-dimethylaminoethyl chloride hydrochloride (87 mg), potassium carbonate (0.65 g), and sodium iodide (7 mg) were stirred in acetone (8 ml) at 60° C. for 16 hours. The reaction mixture was filtered, the solids washed with acetone, and the filtrate was concentrated. The residue was dissolved in ethyl acetate and washed with 2N NaOH solution, brine, dried (magnesium sulfate) and concentrated. Purification by column chromatography on a silica column eluting with 10% methanol/ethyl acetate+1% aqueous ammonia solution gave N-cyclopropyl-3-[7-[2-(dimethylamino)ethoxy]-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzamide (0.137 g) as a white solid; NMR Spectrum: (DMSOd6) 0.57 (m, 2H), 0.69 (m, 2H), 2.10 (s, 3H), 2.23 (s, 6H), 2.68 (t, 2H), 2.85 (m, 1H), 4.19 (m, 2H), 6.72 (d, 1H), 7.21 (d, 1H), 7.41 (d, 1H), 7.49 (d, 1H), 7.68 (s, 1H), 7.71 (d, 1H), 7.75 (s, 1H), 7.88 (d, 1H), 8.43 (d, 1H): Mass Spectrum: M+H+ 406.

Workup

  1. filtrationThe reaction mixture was filtered
  2. washthe solids washed with acetone
  3. concentrationthe filtrate was concentrated
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washwashed with 2N NaOH solution, brine
  6. dry with materialdried (magnesium sulfate)
  7. concentrationconcentrated
  8. customPurification by column chromatography on a silica column
  9. washeluting with 10% methanol/ethyl acetate+1% aqueous ammonia solution

Sources & evidence

ORD record
ord-8cac3fb5c86f43d4bf0646c16815c05c
Source dataset
uspto-grants-2010_08
Patent number
US07786115B2

Reaction notes

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