Lithium Hydroxide → HCID 178437778, compound

HRID 1620268Notes

Reaction equation

HRID 1620268 reaction equation
Cl.Cl[CH2:3][C:4]1[C:5]([NH:16][CH2:17][CH2:18][NH:19][C:20](=[O:22])[CH3:21])=[N:6][C:7]2[C:12]([CH:13]=1)=[CH:11][C:10]([O:14][CH3:15])=[CH:9][CH:8]=2.OCC1C(NCCNC(=O)C)=NC2C(C=1)=CC(OC)=CC=2.[CH2:44]([C:46]1[C:55]2[C:50](=[CH:51][C:52]([O:58][CH3:59])=[C:53]([O:56][CH3:57])[CH:54]=2)[CH:49]=[C:48]([OH:60])[N:47]=1)[CH3:45].[Li+].[OH-]>C1COCC1.C(Cl)Cl>[CH2:44]([C:46]1[C:55]2[C:50](=[CH:51][C:52]([O:58][CH3:59])=[C:53]([O:56][CH3:57])[CH:54]=2)[C:49]([CH2:3][C:4]2[C:5]([NH:16][CH2:17][CH2:18][NH:19][C:20](=[O:22])[CH3:21])=[N:6][C:7]3[C:12]([CH:13]=2)=[CH:11][C:10]([O:14][CH3:15])=[CH:9][CH:8]=3)=[C:48]([OH:60])[N:47]=1)[CH3:45]

Participants

7

Reactant 4

HCID 3939Lithium HydroxideHCID 68182138HCID 68182138, compoundHCID 68182226HCID 68182226, compoundHCID 178437769HCID 178437769, compound2×

Product 1

HCID 178437778HCID 178437778, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
160 °C

Procedure

To a stirred solution of N-(2-(3-(chloromethyl)-6-methoxyquinolin-2-ylamino)ethyl)acetamide hydrochloride SLA 41174 (350 mg, 1.02 mmol) in THF (10 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added 1-ethyl-6,7-dimethoxyisoquinolin-3-ol SLA 28136 (237 mg, 1.02 mmol) followed by a 2 N aq. LiOH solution (1.02 mL, 2.0 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), 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 90:10) provided N-(2-(3-((1-ethyl-3-hydroxy-6,7-dimethoxyisoquinolin-4-yl)methyl)-6-methoxyquinolin-2-ylamino)ethyl)acetamide. The product 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 (2 mL) and the solution was stirred for 5 min at RT then concentrated at 40° C. under vacuum to give N-(2-(3-((1-ethyl-3-hydroxy-6,7-dimethoxyisoquinolin-4-yl)methyl)-6-methoxyquinolin-2-ylamino)ethyl)acetamide dihydrochloride 69 as a yellow solid (83.5 mg, 17% 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 CH2Cl2:MeOH=100:0 to 90:10)

Sources & evidence

ORD record
ord-86072ea2c91b4a5882846902f236c48a
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

Loading…