Lithium Hydroxide → HCID 178437770, compound

HRID 1620251Notes

Reaction equation

HRID 1620251 reaction equation
[CH2:1]([C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15][CH3:16])=[C:10]([O:13][CH3:14])[CH:11]=2)[CH:6]=[C:5]([OH:17])[N:4]=1)[CH3:2].[Li+].[OH-].Cl.Cl[CH2:22][C:23]1[C:24]([NH:36][CH3:37])=[N:25][C:26]2[CH:27]=[C:28]3[O:35][CH2:34][O:33][C:29]3=[CH:30][C:31]=2[CH:32]=1>C1(C)C=CC=CC=1.C(Cl)Cl>[CH2:1]([C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15][CH3:16])=[C:10]([O:13][CH3:14])[CH:11]=2)[C:6]([CH2:22][C:23]2[C:24]([NH:36][CH3:37])=[N:25][C:26]3[CH:27]=[C:28]4[O:35][CH2:34][O:33][C:29]4=[CH:30][C:31]=3[CH:32]=2)=[C:5]([OH:17])[N:4]=1)[CH3:2]

Participants

6

Reactant 3

HCID 3939Lithium HydroxideHCID 68182129HCID 68182129, compound2×HCID 178437769HCID 178437769, compound2×

Product 1

HCID 178437770HCID 178437770, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 1-ethyl-6,7-dimethoxyisoquinolin-3-ol SLA 28136 (284 mg, 1.22 mmol) in toluene (10 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added a 2 N aq. LiOH solution (1.20 mL, 2.40 mmol) at RT followed by 7-(chloromethyl)-N-methyl-[1,3]dioxolo[4,5-g]quinolin-6-amine hydrochloride CCH 34158B (350 mg, 1.22 mmol) and the mixture was stirred at 150° C. for 1.5 h under microwave irradiation. After cooling to RT, the mixture was diluted with CH2Cl2:MeOH=9:1 (80 mL) and the organic solution was washed with 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 1-ethyl-6,7-dimethoxy-4-((6-(methylamino)-[1,3]dioxolo[4,5-g]quinolin-7-yl)methyl)isoquinolin-3-ol. This free base was dissolved in MeOH (6 mL) in a 25 mL round-bottomed flask equipped with a magnetic stirrer before addition of a 0.19 M HCl solution in MeOH (5 mL). The reaction mixture was stirred for 5 min at RT and concentrated at 40° C. under vacuum. Recrystallization from a mixture of MeOH:Et2O afforded 1-ethyl-6,7-dimethoxy-4-((6-(methylamino)-[1,3]dioxolo[4,5-g]quinolin-7-yl)methyl)isoquinolin-3-ol dihydrochloride 61 as a pale brown solid (104 mg, 16% yield).

Workup

  1. temperatureAfter cooling to RT
  2. washMeOH=9:1 (80 mL) and the organic solution was washed with brine (10 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated at 40° C. under vacuum
  6. customPurification by column chromatography (SiO2, eluent CH2Cl2:7 N NH3 solution in MeOH=100:0 to 95:5)

Sources & evidence

ORD record
ord-2182460df3d24af48efacc79a761a62e
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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