Lithium Hydroxide → HCID 178440230, compound

HRID 1620309Notes

Reaction equation

HRID 1620309 reaction equation
Cl.Cl[CH2:3][C:4]1[C:5]([NH:17][CH2:18][CH2:19][NH:20][C:21](=[O:23])[CH3:22])=[N:6][C:7]2[C:12]([CH:13]=1)=[CH:11][C:10]([O:14][CH2:15][CH3:16])=[CH:9][CH:8]=2.[CH3:24][O:25][C:26]1[CH:27]=[C:28]2[C:33](=[CH:34][C:35]=1[O:36][CH3:37])[C:32]([CH2:38][CH2:39][CH3:40])=[N:31][C:30]([OH:41])=[CH:29]2.[Li+].[OH-]>C1COCC1.C(Cl)Cl>[CH2:15]([O:14][C:10]1[CH:11]=[C:12]2[C:7](=[CH:8][CH:9]=1)[N:6]=[C:5]([NH:17][CH2:18][CH2:19][NH:20][C:21](=[O:23])[CH3:22])[C:4]([CH2:3][C:29]1[C:28]3[C:33](=[CH:34][C:35]([O:36][CH3:37])=[C:26]([O:25][CH3:24])[CH:27]=3)[C:32]([CH2:38][CH2:39][CH3:40])=[N:31][C:30]=1[OH:41])=[CH:13]2)[CH3:16]

Participants

6

Reactant 3

HCID 3939Lithium HydroxideHCID 68182336HCID 68182336, compoundHCID 178440211HCID 178440211, compound

Product 1

HCID 178440230HCID 178440230, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
160 °C

Procedure

To a stirred solution of N-(2-(3-(chloromethyl)-6-ethoxyquinolin-2-ylamino)ethyl)acetamide hydrochloride SMA 44092 (231 mg, 0.65 mmol) in THF (10 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added 6,7-dimethoxy-1-propylisoquinolin-3-ol RBO 35134 (159 mg, 0.65 mmol) followed by a 2 N aq. LiOH solution (0.65 mL, 1.29 mmol) and the mixture was stirred at 160° C. for 1.5 h under microwave irradiation. After cooling to RT, the mixture was diluted with CH2Cl2:MeOH=9:1 (150 mL) and washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 93:7) provided N-(2-(6-ethoxy-3-((3-hydroxy-6,7-dimethoxy-1-propylisoquinolin-4-yl)methyl)quinolin-2-ylamino)ethyl)acetamide. This free base was dissolved in CH2Cl2 (2 mL) in a 10 mL round-bottomed flask equipped with a magnetic stirrer before addition of 0.49 M HCl in MeOH (2 mL) and the solution was stirred for 5 min at RT then concentrated at 40° C. under vacuum to afford N-(2-(6-ethoxy-3-((3-hydroxy-6,7-dimethoxy-1-propylisoquinolin-4-yl)methyl)quinolin-2-ylamino)ethyl)acetamide dihydrochloride 88 as a yellow solid (25 mg, 6% yield).

Workup

  1. temperatureAfter cooling to RT
  2. washMeOH=9:1 (150 mL) and 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 CH2Cl2:MeOH=100:0 to 93:7)

Sources & evidence

ORD record
ord-c56d4f4274df48e990c29886d7f41892
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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