3-(chloromethyl)-N,N,6-trimethylquinolin-2-amine hydrochloride → HCID 178440218, compound

HRID 1620195Notes

Reaction equation

HRID 1620195 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.[ClH:19].[Cl:20][CH2:21][C:22]1[C:23]([N:33]([CH3:35])[CH3:34])=[N:24][C:25]2[C:30]([CH:31]=1)=[CH:29][C:28]([CH3:32])=[CH:27][CH:26]=2>C1(C)C=CC=CC=1>[ClH:20].[ClH:19].[CH3:34][N:33]([CH3:35])[C:23]1[C:22]([CH2:21][C:6]2[C:5]3[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=3)[C:9]([CH2:15][CH2:16][CH3:17])=[N:8][C:7]=2[OH:18])=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[C:28]([CH3:32])[CH:29]=2)[N:24]=1

Participants

4

Reactant 2

HCID 681823133-(chloromethyl)-N,N,6-trimethylquinolin-2-amine hydrochloride2×HCID 178440211HCID 178440211, compound2×

Product 1

HCID 178440218HCID 178440218, compoundYield 6.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
150 °C

Procedure

To a stirred solution of 6,7-dimethoxy-1-propylisoquinolin-3-ol RBO 35142 (173 mg, 0.638 mmol) in toluene (10 mL) in a 100 mL round-bottomed flask equipped with a magnetic stirrer was added 3-(chloromethyl)-N,N,6-trimethylquinolin-2-amine hydrochloride RBO 35154 (158 mg, 0.638 mmol) and the mixture was stirred at 150° C. for 1.5 h. After cooling to RT, the volatiles were removed and the residue was taken back in CH2Cl2 (20 mL). This solution was washed with water (3×10 mL), brine (10 mL), dried over Na2SO4, filtered, and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent CH2Cl2:7 N NH3 solution in MeOH=100:0 to 95:5) gave after evaporation 20.2 mg of 4-((2-(dimethylamino)-6-methylquinolin-3-yl)methyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol as a yellow solid. The free base was dissolved in MeOH (2 mL) and converted into salt by addition of a 0.19 M HCl solution in MeOH (0.525 mL). The reaction mixture was stirred for 5 min at RT then concentrated at 40° C. under vacuum to afford 4-(2-dimethylamino-6-methyl-quinolin-3-ylmethyl)-6,7-dimethoxy-1-propyl-soquinolin-3-ol dihydrochloride 36 as a yellow solid (22.2 mg, 6.7% yield).

Workup

  1. temperatureAfter cooling to RT
  2. customthe volatiles were removed
  3. washThis solution was washed with water (3×10 mL), brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated at 40° C. under vacuum
  7. customPurification by column chromatography (SiO2, eluent CH2Cl2:7 N NH3 solution in MeOH=100:0 to 95:5)
  8. customgave
  9. customafter evaporation 20.2 mg of 4-((2-(dimethylamino)-6-methylquinolin-3-yl)methyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol as a yellow solid
  10. dissolutionThe free base was dissolved in MeOH (2 mL)
  11. additionconverted into salt by addition of a 0.19 M HCl solution in MeOH (0.525 mL)
  12. stirringThe reaction mixture was stirred for 5 min at RT
  13. concentrationthen concentrated at 40° C. under vacuum

Sources & evidence

ORD record
ord-79f416cdb220438dad35f5c53dfd0b94
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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