Sodium hydride → HCID 66835837, compound

HRID 572889Notes

Reaction equation

[I:1][C:2]1[CH:3]=[C:4]([CH:8]([O:18][CH:19]2[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]2)[C:9]2[NH:13][C:12]3[CH:14]=[CH:15][CH:16]=[CH:17][C:11]=3[N:10]=2)[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].Br[CH2:29][CH2:30][O:31][CH2:32][CH3:33]>C(#N)C.CC(C)=O>[CH2:30]([O:31][CH2:32][CH2:33][N:10]1[C:11]2[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=2[N:13]=[C:9]1[CH:8]([C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([I:1])[CH:3]=1)[O:18][CH:19]1[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]1)[CH3:29]

Participants

Conditions

Temperature: 60 °C

Procedure

A solution of 2-[(3-iodophenyl)(1-methylpiperidin-4-yloxy)methyl]-1H-benzimidazole (example 51, 260 mg) in anhydrous acetonitrile (10 mL) is treated with 60% sodium hydride (47 mg) for 30 min at room temperature. 1-Bromo-2-ethoxyethane (84 μL) is then introduced. After warming at 60° C. for 8 h, dilution with water and extraction with diethylether, the organic phase is dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography over silica gel (gradient dichloromethane/methanol/ammonia from 98/2/0.5 to 95/5/0.5) to afford the pure base that is then converted into its dioxalate salt in acetone to give 1-(2-ethoxyethyl)-2-[(3-iodophenyl)(1-methylpiperidin-4-yloxy)methyl]-1H-benzimidazole, dioxalate, melting at 88° C.

Workup

extractiondilution with water and extraction with diethylether
dry with materialthe organic phase is dried over magnesium sulfate
concentrationconcentrated under reduced pressure
customThe residue is purified by chromatography over silica gel (gradient dichloromethane/methanol/ammonia from 98/2/0.5 to 95/5/0.5)
customto afford the pure base that

Sources & evidence

ORD record: ord-d0a69bf86d0b4781a4ae199ad6a95aaa
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09029357B2

Reaction notes

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