Hydrochloric Acid → HCID 178440216, compound

HRID 1620189Notes

Reaction equation

HRID 1620189 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[C:9]([CH2:15][CH2:16][CH3:17])=[N:8][C:7]([OH:18])=[CH:6]2.[OH-].[K+].[ClH:21].[Cl:22][CH2:23][C:24]1[C:25]([NH:35][CH3:36])=[N:26][C:27]2[C:32]([CH:33]=1)=[CH:31][C:30]([CH3:34])=[CH:29][CH:28]=2.Cl.CO>C1(C)C=CC=CC=1>[ClH:22].[ClH:21].[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[C:9]([CH2:15][CH2:16][CH3:17])=[N:8][C:7]([OH:18])=[C:6]2[CH2:23][C:24]1[C:25]([NH:35][CH3:36])=[N:26][C:27]2[C:32]([CH:33]=1)=[CH:31][C:30]([CH3:34])=[CH:29][CH:28]=2

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14797Potassium HydroxideHCID 681822193-(chloromethyl)-N,6-dimethylquinolin-2-amine hydrochloride2×HCID 178440211HCID 178440211, compound2×

Product 1

HCID 178440216HCID 178440216, compoundYield 5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
160 °C

Procedure

To a solution of 6,7-dimethoxy-1-propylisoquinolin-3-ol RBO 35142 (250 mg, 1 mmol) in toluene (15 mL) in a 20 mL microwave vial was added a 2 N KOH solution (1 mL, 2 mmol) following by 3-(chloromethyl)-N,6-dimethylquinolin-2-amine hydrochloride MDE 32062 (352 mg, 1.2 mmol). The reaction mixture was stirred at 160° C. for 1.5 h under microwave irradiation then cooled to RT. The volatiles were removed under vacuum and the residue was taken back in a mixture of CH2Cl2:MeOH=9:1 (50 mL). The organic layer was washed with water (3×20 mL), brine (20 mL), dried over Na2SO4, filtered and evaporated to give yellow solid that was purified by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 90:10) to give, after evaporation and drying, 6,7-dimethoxy-4-(6-methyl-2-methylamino-quinolin-3-ylmethyl)-1-propyl-isoquinolin-3-ol (26 mg). This free base was dissolved in MeOH (5 mL) and a 0.19 N HCl solution in MeOH (600 μL, 0.11 mmol) was slowly added. The reaction mixture was stirred at 4° C. for 15 min. After evaporation of the solvent and drying under vacuum pump over P2O5, 6,7-dimethoxy-4-((6-methyl-2-(methylamino)quinolin-3-yl)methyl)-1-propylisoquinolin-3-ol hydrochloride 34 was obtained as a yellow solid (28.7 mg, 5% yield).

Workup

  1. temperaturethen cooled to RT
  2. customThe volatiles were removed under vacuum
  3. additionthe residue was taken back in a mixture of CH2Cl2
  4. washThe organic layer was washed with water (3×20 mL), brine (20 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customto give yellow solid
  9. customthat was purified by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 90:10)
  10. customto give
  11. customafter evaporation
  12. customdrying
  13. dissolutionThis free base was dissolved in MeOH (5 mL)
  14. stirringThe reaction mixture was stirred at 4° C. for 15 min
  15. customAfter evaporation of the solvent
  16. dry with materialdrying under vacuum pump over P2O5

Sources & evidence

ORD record
ord-84951ba294f841eb9d175a1a6a0da8a7
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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