Acetic Acid → 2-(4-tert-butylphenyl)-N-[(E)-isoquinolin-5-ylmethylideneamino]cyclopropane-1-carboxamide

HRID 446762

Reaction equation

HRID 446762 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[CH2:13][CH:12]2[C:14]([NH:16][NH2:17])=[O:15])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH:18]1[C:27]2[CH:26]=[CH:25][CH:24]=[C:23]([CH:28]=O)[C:22]=2[CH:21]=[CH:20][N:19]=1.CC(O)=O>C(O)C>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[CH2:13][CH:12]2[C:14]([NH:16]/[N:17]=[CH:28]/[C:23]2[CH:24]=[CH:25][CH:26]=[C:27]3[C:22]=2[CH:21]=[CH:20][N:19]=[CH:18]3)=[O:15])=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 5891992-(4-tert-Butylphenyl)cyclopropanecarbohydrazideHCID 7016853Isoquinoline-5-carboxaldehyde

Product 1

HCID 445554402-(4-tert-butylphenyl)-N-[(E)-isoquinolin-5-ylmethylideneamino]cyclopropane-1-carboxamideYield 50.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

To a room temperature solution of 2-(4-tert-butylphenyl)cyclopropanecarbohydrazide (200 mg, 0.86 mmol) in ethanol (10 mL) were added isoquinoline-5-carbaldehyde (162 mg, 1.0 mmol) and a catalytic amount of glacial AcOH (0.4 mL) under an inert atmosphere. The reaction mixture was then stirred at 90° C. for 4 h, concentrated in vacuo, and the residue was then dissolved in DCM (50 mL). The organic layer was washed with saturated NaHCO3 solution (15 mL) and brine (15 mL). The organic layer was then separated, dried over anhydrous Na2SO4, filtered and evaporated in vacuo to obtain the crude product. The crude material was purified via silica gel column chromatography eluting with 1% MeOH in dichloromethane to afford (E)-2-(4-tert-butylphenyl)-N′-(isoquinolin-5-ylmethylene) cyclopropanecarbohydrazide (160 mg, 50%) as a white solid. 1H NMR (500 MHz, d6-DMSO): δ 11.60 (s, 1H), 9.38 (s, 1H), 8.71-8.56 (m, 2H), 8.25-8.12 (m, 2H), 8.11-7.99 (m, 2H), 7.39-7.29 (m, 2H), 7.19-7.06 (m, 2H), 2.41-2.33 (m, 1H), 1.95-1.90 (m, 1H), 1.42-1.34 (m, 2H), 1.25 (s, 9H). MS: M m/z=372.2 HPLC: 96%, (Condition-A).

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionthe residue was then dissolved in DCM (50 mL)
  3. washThe organic layer was washed with saturated NaHCO3 solution (15 mL) and brine (15 mL)
  4. customThe organic layer was then separated
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customto obtain the crude product
  9. customThe crude material was purified via silica gel column chromatography
  10. washeluting with 1% MeOH in dichloromethane

Sources & evidence

ORD record
ord-577731232e1945eb8b755f45afb7bd17
Source dataset
uspto-grants-2013_07
Patent number
US08481532B2

Linked notes

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