Sodium Methoxide → 4-((4-Chloro-6-iodo-2-methoxyquinolin-3-yl)methyl)-N,N-dimethylaniline

HRID 926484Notes

Reaction equation

[CH3:1][O-:2].[Na+].Cl[C:5]1[C:14]([CH2:15][C:16]2[CH:24]=[CH:23][C:19]([N:20]([CH3:22])[CH3:21])=[CH:18][CH:17]=2)=[C:13]([Cl:25])[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([I:26])[CH:11]=2)[N:6]=1>C1(C)C=CC=CC=1>[Cl:25][C:13]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([I:26])[CH:11]=2)[N:6]=[C:5]([O:2][CH3:1])[C:14]=1[CH2:15][C:16]1[CH:24]=[CH:23][C:19]([N:20]([CH3:22])[CH3:21])=[CH:18][CH:17]=1

Participants

Conditions

Temperature: 110 °C

Procedure

Sodium methoxide (2.9 g, 54 mmol) was added to a solution of 4-((2,4-dichloro-6-iodoquinolin-3-yl)methyl)-N,N-dimethylaniline (3.5 g, 7.7 mmol, Intermediate 24: step b) in toluene (38 mL) with stirring. The mixture was heated to 110° C. After 3 hours, additional sodium methoxide (2 g, 37.2 mmol) was added. After 18 hours, the flask was allowed to cool to 50° C. The warm mixture was filtered through Celite®, rinsing with tetrahydrofuran. Silica gel (5 g) was added to the filtrate and the solvent was removed by rotary evaporation to afford a free-flowing powder. The powder was loaded onto a column of silica gel for purification. Elution with dichloromethane initially, grading to 1% methanol-dichloromethane provided the title compound as a solid.

Workup

waitAfter 18 hours
temperatureto cool to 50° C
filtrationThe warm mixture was filtered through Celite®
washrinsing with tetrahydrofuran
additionSilica gel (5 g) was added to the filtrate
customthe solvent was removed by rotary evaporation
customto afford a free-flowing powder
customThe powder was loaded onto a column of silica gel for purification
washElution with dichloromethane initially

Sources & evidence

ORD record: ord-937dc8fbc5ea415ea69b74669deba6f9
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09284308B2

Reaction notes

Loading…