Hydrochloric Acid → 1-(3,5-Dimethylanilino)-4-[(pyridin-4-yl)-methyl]-isoquinoline

HRID 396213Notes

Reaction equation

HRID 396213 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([CH3:9])[CH:8]=1)[NH2:5].Cl.Cl[C:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]([CH2:22][C:23]2[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=2)=[CH:14][N:13]=1>C(O)C>[CH3:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([CH3:9])[CH:8]=1)[NH:5][C:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]([CH2:22][C:23]2[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=2)=[CH:14][N:13]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 79493,5-DimethylanilineHCID 111611391-Chloro-4-(pyridin-4-ylmethyl)-isoquinoline

Product 1

HCID 98627391-(3,5-Dimethylanilino)-4-[(pyridin-4-yl)-methyl]-isoquinoline

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

With the exclusion of moisture, 100 mg (0.825 mmol) of 3,5-dimethyl-aniline are dissolved in 4 ml of ethanol, and 196 μl (0.784 mmol) of HCl (4N in dioxane) are added. After the addition of 200 mg (0.785 mmol) of 1-chloro-4-[(pyridin-4-yl)-methyl]-isoquinoline, the mixture is heated for 8 hours at 90° C. Concentration by evaporation is then carried out; the residue is taken up in 4 ml of water, 1 ml of saturated ammonia solution and 20 ml of CH2Cl2, and the organic phase is separated off, dried with Na2SO4 (anhydrous) and concentrated by evaporation again. Column chromatography (SiO2; ethyl acetatelhexane 3:1) and crystallisation from ethyl acetate/hexane yield the title compound: m.p. 156-158° C.; 1H NMR (DMSO-d6) 9.00 (s, HN), 8.54 (d, 1H), 8.42 (d, 2H), 8.00 (s, 1H), 7.80 (d, 1H), 7.65 (m, 2H), 7.50 (s, 2H), 7.26 (d, 2H), 6.64 (s, 1H), 4.25 (s, 2H), 2.27 (s, 6H); FAB-MS: (M+H)+=340; Anal. calc. (C23H21N3.0.1H2O) C 80.95%, H 6.26%, N 12.31%; found C 80.9%, H 6.2%, N 12.4%.

Workup

  1. concentrationConcentration
  2. customby evaporation
  3. custom1 ml of saturated ammonia solution and 20 ml of CH2Cl2, and the organic phase is separated off
  4. dry with materialdried with Na2SO4 (anhydrous)
  5. concentrationconcentrated by evaporation again
  6. customColumn chromatography (SiO2; ethyl acetatelhexane 3:1) and crystallisation from ethyl acetate/hexane

Sources & evidence

ORD record
ord-82755828494e44848017c4522911c709
Source dataset
uspto-grants-2003_08
Patent number
US06608071B2

Reaction notes

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