Ammonia → HCID 178463389, compound

HRID 1620245Notes

Reaction equation

HRID 1620245 reaction equation
C([O:4][C:5]1[N:6]=[C:7]([CH2:35][NH:36][C:37](=[O:39])[CH3:38])[C:8]2[C:13]([C:14]=1[CH2:15][C:16]1[C:17]([NH:28][CH2:29][CH3:30])=[N:18][C:19]3[C:24]([CH:25]=1)=[CH:23][C:22]([O:26][CH3:27])=[CH:21][CH:20]=3)=[CH:12][C:11]([O:31][CH3:32])=[C:10]([O:33][CH3:34])[CH:9]=2)(=O)C.N>C(Cl)Cl.CO>[CH2:29]([NH:28][C:17]1[C:16]([CH2:15][C:14]2[C:13]3[C:8](=[CH:9][C:10]([O:33][CH3:34])=[C:11]([O:31][CH3:32])[CH:12]=3)[C:7]([CH2:35][NH:36][C:37](=[O:39])[CH3:38])=[N:6][C:5]=2[OH:4])=[CH:25][C:24]2[C:19](=[CH:20][CH:21]=[C:22]([O:26][CH3:27])[CH:23]=2)[N:18]=1)[CH3:30]

Participants

5

Reactant 2

HCID 222AmmoniaHCID 601638771-(Acetamidomethyl)-4-((2-(ethylamino)-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxyisoquinolin-3-yl acetate

Product 1

HCID 178463389HCID 178463389, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1-(acetamidomethyl)-4-((2-(ethylamino)-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxyisoquinolin-3-yl acetate 56 (20 mg, 38 μmol) in CH2Cl2 (9 mL) in a 25 mL round-bottomed flask equipped with a magnetic stirrer was added a 7 N NH3 solution in MeOH (1 mL) and the reaction mixture was stirred overnight at RT then diluted with CH2Cl2:MeOH=9:1 (50 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:MeOH=100:0 to 90:10) gave N-((4-((2-(ethylamino)-6-methoxyquinolin-3-yl)methyl)-3-hydroxy-6,7-dimethoxyisoquinolin-1-yl)methyl)acetamide. The free base was dissolved in MeOH (3 mL) in a 10 mL round-bottomed flask equipped with a magnetic stirrer before addition of a 0.4 M HCl solution in MeOH (1 mL). The reaction mixture was stirred for 5 min at RT and concentrated at 40° C. under vacuum to afford N-((4-((2-(ethylamino)-6-methoxyquinolin-3-yl)methyl)-3-hydroxy-6,7-dimethoxyisoquinolin-1-yl)methyl)acetamide dihydrochloride 57 as a pale yellow solid (17 mg, 79% yield).

Workup

  1. washMeOH=9:1 (50 mL) and the organic solution was washed with brine (10 mL)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated at 40° C. under vacuum
  5. customPurification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 90:10)

Sources & evidence

ORD record
ord-cce49dde7af34878b503923f52253933
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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