Lithium Hydroxide → HCID 178440224, compound

HRID 1620235Notes

Reaction equation

HRID 1620235 reaction equation
Cl.Cl[CH2:3][C:4]1[C:5]([NH:16][CH:17]([CH3:19])[CH3:18])=[N:6][C:7]2[C:12]([CH:13]=1)=[CH:11][C:10]([O:14][CH3:15])=[CH:9][CH:8]=2.[CH3:20][O:21][C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][C:31]=1[O:32][CH3:33])[C:28]([CH2:34][CH2:35][CH3:36])=[N:27][C:26]([OH:37])=[CH:25]2.[Li+].[OH-]>C1(C)C=CC=CC=1.C(Cl)Cl>[CH:17]([NH:16][C:5]1[C:4]([CH2:3][C:25]2[C:24]3[C:29](=[CH:30][C:31]([O:32][CH3:33])=[C:22]([O:21][CH3:20])[CH:23]=3)[C:28]([CH2:34][CH2:35][CH3:36])=[N:27][C:26]=2[OH:37])=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:14][CH3:15])[CH:11]=2)[N:6]=1)([CH3:19])[CH3:18]

Participants

6

Reactant 3

HCID 3939Lithium HydroxideHCID 681822153-(Chloromethyl)-N-isopropyl-6-methoxyquinolin-2-amine hydrochloride2×HCID 178440211HCID 178440211, compound

Product 1

HCID 178440224HCID 178440224, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °C

Procedure

To a stirred solution of 3-(chloromethyl)-N-isopropyl-6-methoxyquinolin-2-amine hydrochloride SLA 28190 (305 mg, 1.01 mmol) in toluene (10 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added 6,7-dimethoxy-1-propylisoquinolin-3-ol RBO 35134 (250 mg, 1.01 mmol) followed by a 2 N aq. LiOH solution (1.01 mL, 2.02 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 (150 mL), washed with brine (20 mL), dried over Na2SO4, filtered and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent EtOAc:MeOH=100:0 to 94:6) followed by a second purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 95:5) provided 61 mg of 4-((2-(isopropylamino)-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol as a brown solid. This free base was dissolved in CH2Cl2 (2 mL) in a 10 mL round-bottomed flask equipped with a magnetic stirrer before addition of a 0.49 M HCl solution in MeOH (1.05 mL). The reaction mixture was stirred for 5 min at RT then concentrated at 40° C. under vacuum to afford 4-((2-(isopropylamino)-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol dihydrochloride 53 as a yellow solid (68 mg, 12% yield).

Workup

  1. temperatureAfter cooling to RT
  2. washMeOH=9:1 (150 mL), washed with brine (20 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated at 40° C. under vacuum
  6. customPurification by column chromatography (SiO2, eluent EtOAc:MeOH=100:0 to 94:6)
  7. customfollowed by a second purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 95:5)

Sources & evidence

ORD record
ord-bda529c8d8d344fb8bd3873a6f4c8cc3
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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