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

HRID 506990Notes

Reaction equation

HRID 506990 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:22]=[CH:23][C:24]=3[CH3:25])[C:19]([OH:21])=[O:20])[C:12]2=[O:15])=[CH:7][CH:6]=1.C[CH2:27][N:28](C(C)C)[CH:29]([CH3:31])[CH3:30].[I-].[K+].CNC(C)C.[N-]=C=O>CC(N(C)C)=O.C(Cl)Cl>[CH:29]([N:28]([CH3:27])[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:22]=[CH:23][C:24]=3[CH3:25])[C:19]([OH:21])=[O:20])[C:12]2=[O:15])=[CH:7][CH:6]=1)([CH3:31])[CH3:30]

Participants

8

Reactant 5

HCID 4875Potassium IodideHCID 78485N-MethylisopropylamineHCID 81531DiisopropylethylamineHCID 105034IsocyanateHCID 670185953-[7-(2-chloroethoxy)-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzoic acid

Product 1

HCID 670185933-[7-{2-[isopropyl(methyl)amino]ethoxy}-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzoic acid

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 31374DimethylacetamideSolvent

Procedure

3-[7-(2-chloroethoxy)-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzoic acid (504 mg), DIPEA (0.7 ml), potassium iodide (332 mg) and N-methylisopropylamine (0.42 ml) in DMA (4 ml) was heated under microwave irradiation conditions (Personal Chemistry Emrys Optimizer with 300 W magnetron) at 120° C. for 30 minutes. The mixture was diluted with methylene chloride (25 ml), isocyanate resin (CombiZorb) (7.67 g) was added and stirred at room temperature for 18 hours. The resin was removed by filtration and the filtrate was washed with water. The aqueous phase 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 3-[7-{2-[isopropyl(methyl)amino]ethoxy}-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzoic acid as a pale brown solid (110 mg); NMR Spectrum: (DMSOd6) 1.00 (m, 6H), 2.15 (s, 3H), 2.30 (s, 3H), 2.45 (s, 1H), 2.85 (m, 2H), 4.15 (m, 2H), 6.70 (m, 1H), 7.20 (m, 1H), 7.40 (m, 1H), 7.55 (m, 1H), 7.70 (m, 2H), 7.80 (m, 1H), 7.95 (m, 1H); Mass Spectrum: M+H+ 395.

Workup

  1. additionwas added
  2. customThe resin was removed by filtration
  3. washthe filtrate was washed with water
  4. customThe aqueous phase was purified by column chromatography on an ion exchange column (isolute SCX column from International Sorbent Technology Limited, Henoed, Mid-Glamorgan, UK)
  5. additiona 99:1 mixture of methanol and aqueous ammonia solution

Sources & evidence

ORD record
ord-7097e5ada7994541b30f95132dd944a1
Source dataset
uspto-grants-2010_08
Patent number
US07786115B2

Reaction notes

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