Hydrochloric Acid → HCID 178440213, compound

HRID 1620254Notes

Reaction equation

HRID 1620254 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.O[Li].O.[ClH:22].[Cl:23][CH2:24][C:25]1[C:26]([N:38]([CH3:40])[CH3:39])=[N:27][C:28]2[CH:29]=[C:30]3[O:37][CH2:36][O:35][C:31]3=[CH:32][C:33]=2[CH:34]=1.Cl.CO>C1(C)C=CC=CC=1>[ClH:23].[ClH:22].[CH3:40][N:38]([CH3:39])[C:26]1[C:25]([CH2:24][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:34][C:33]2[CH:32]=[C:31]3[O:35][CH2:36][O:37][C:30]3=[CH:29][C:28]=2[N:27]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 168937Lithium hydroxide, monohydrateHCID 68182217HCID 68182217, compoundHCID 178440211HCID 178440211, compound2×

Product 1

HCID 178440213HCID 178440213, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 6,7-dimethoxy-1-propylisoquinolin-3-ol RBO 35142 (250 mg, 1.0 mmol) in toluene in a 20 mL microwave vial was added LiOH.H2O (84 mg, 2.0 mmol) and 7-(chloromethyl)-N,N-dimethyl-[1,3]dioxolo[4,5-g]quinolin-6-amine hydrochloride RBO 35172 (301 mg, 1.0 mmol). The mixture was stirred at 150° 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 dichloromethane (30 mL), washed with water (3×10 mL), brine (10 mL), dried over Na2SO4, filtered and evaporated to give an orange solid. This solid was purified by column chromatography (SiO2, eluent CH2Cl2:7 N NH3 solution in MeOH=100:0 to 95:5) to give after evaporation and drying 4-((6-(dimethylamino)-[1,3]dioxolo[4,5-g]quinolin-7-yl)methyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol (142 mg). This free base was dissolved in MeOH (5 mL) and a HCl 0.19 N solution in MeOH (1.35 mL, 0.26 mmol) was slowly added. The reaction mixture was stirred at 4° C. for 15 min. After evaporation and drying under vacuum pump under P2O5, 4-((6-(dimethylamino)-[1,3]dioxolo[4,5-g]quinolin-7-yl)methyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol dihydrochloride 63 was obtained as a yellow solid (148 mg, 55% yield).

Workup

  1. temperaturethen cooled to RT
  2. customThe volatiles were removed under vacuum
  3. washwashed with water (3×10 mL), brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customto give an orange solid
  8. customThis solid was purified by column chromatography (SiO2, eluent CH2Cl2:7 N NH3 solution in MeOH=100:0 to 95:5)
  9. customto give
  10. customafter evaporation
  11. dry with materialdrying 4-((6-(dimethylamino)-[1,3]dioxolo[4,5-g]quinolin-7-yl)methyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol (142 mg)
  12. dissolutionThis free base was dissolved in MeOH (5 mL)
  13. stirringThe reaction mixture was stirred at 4° C. for 15 min
  14. customAfter evaporation
  15. customdrying under vacuum pump under P2O5

Sources & evidence

ORD record
ord-4af103a460214297914c40bfe4b99d5b
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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