Ethylamine → 3-[7-(2-chloroethoxy)-4-methyl-1-oxoisoquinolin-2(1H)-yl]-N-ethyl-4-methylbenzamide

HRID 507009Notes

Reaction equation

HRID 507009 reaction equation
[Cl:1][CH2:2][CH2:3][O:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9]([CH3:26])=[CH:10][N:11]([C:16]3[CH:17]=[C:18]([CH:22]=[CH:23][C:24]=3[CH3:25])[C:19](O)=[O:20])[C:12]2=[O:15])=[CH:7][CH:6]=1.C(Cl)(=O)C(Cl)=O.[CH3:33][CH2:34][N:35](C(C)C)C(C)C.C(N)C>C(Cl)Cl.C1COCC1.CN(C=O)C>[Cl:1][CH2:2][CH2:3][O:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9]([CH3:26])=[CH:10][N:11]([C:16]3[CH:17]=[C:18]([CH:22]=[CH:23][C:24]=3[CH3:25])[C:19]([NH:35][CH2:34][CH3:33])=[O:20])[C:12]2=[O:15])=[CH:7][CH:6]=1

Participants

8

Reactant 4

HCID 6341EthylamineHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 67018656HCID 67018656, compound

Product 1

HCID 670185833-[7-(2-chloroethoxy)-4-methyl-1-oxoisoquinolin-2(1H)-yl]-N-ethyl-4-methylbenzamide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of 3-[7-(2-chloroethoxy)-4-methyl-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzoic acid (425 mg) in methylene chloride (8 ml) was cooled to 0° C. and oxalyl chloride (0.2 ml) was added followed by DMF (10 μL) and the reaction mixture was left to stir at room temperature for 1 hour when N,N′-diisopropylethylamine (0.8 ml) and ethylamine (2.28 ml of a 2.0M in THF) were added. The reaction mixture was stirred at room temperature for 17 hours and concentrated. The residue was diluted with ethyl acetate and washed with water (×3), brine, dried (magnesium sulfate) and concentrated to a brown foam which was purified by column chromatography on a silica column eluting using a gradient of iso-hexane to ethyl acetate to give 3-[7-(2-chloroethoxy)-4-methyl-1-oxoisoquinolin-2(1H)-yl]-N-ethyl-4-methylbenzamide as a pale yellow solid (323 mg); NMR Spectrum: (DMSOd6) 1.11 (t, 3H), 2.11 (s, 3H), 2.27 (s, 3H), 3.28 (m, 2H), 4.01 (t, 2H), 4.41 (m, 2H), 7.13 (s, 1H), 7.52 (m, 2H), 7.73-7.78 (m, 3H), 7.89 (d, 1H), 8.50 (t, 1H); Mass Spectrum: M+H+ 399.

Workup

  1. waitthe reaction mixture was left
  2. additionwere added
  3. concentrationconcentrated
  4. additionThe residue was diluted with ethyl acetate
  5. washwashed with water (×3), brine
  6. dry with materialdried (magnesium sulfate)
  7. concentrationconcentrated to a brown foam which
  8. customwas purified by column chromatography on a silica column
  9. washeluting

Sources & evidence

ORD record
ord-9eff3815a70c4d52b33a85546f769ee2
Source dataset
uspto-grants-2010_08
Patent number
US07786115B2

Reaction notes

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