Sodium hydride → HCID 178514991, compound

HRID 31740Notes

Reaction equation

[N+:1]([C:4]1[N:5]=[CH:6][NH:7][CH:8]=1)([O-:3])=[O:2].[H-].[Na+].[H][H].BrCCC[C:17]1[CH:27]=[CH:26][CH:25]=[C:19]2[C:20]([NH:22][C:23](=[O:24])[C:18]=12)=[O:21].CN(C=O)C.[CH2:33]1[CH2:37]OC[CH2:34]1>ClCCl>[N+:1]([C:4]1[N:5]=[C:6]([CH2:34][CH2:33][CH2:37][N:22]2[C:23](=[O:24])[C:18]3[C:19](=[CH:25][CH:26]=[CH:27][CH:17]=3)[C:20]2=[O:21])[NH:7][CH:8]=1)([O-:3])=[O:2]

Participants

Conditions

Temperature: 70 °C

Procedure

4-Nitroimidazole (5.0 g, 44 mol) in DMF:THF (1:1 (v/v), 40 ml) was treated at room temperature with 60% NaH (2.2 g). When hydrogen evolution had ceased, 3-bromopropylphthalimide (11.79 g, 44 mmol) was added, followed by heating at 70° C. overnight. The mixture was cooled, diluted with dichloromethane and carefully quenched with water. At this point the solid product precipitated out to give 2-[3-(4-nitroimidazolyl)propyl]isoindoline-1,3-dione as a white solid, 8.85 g. The solid was refluxed with methanol (60 ml) and anhydrous hydrazine (4 ml) overnight. The mixture was cooled to 4° C., then filtered. The filtrate was concentrated to dryness, then partitioned between dichloromethane and 2.5 M aqueous sodium hydroxide. The organic layer was washed with saturated sodium chloride solution, dried and concentrated in vacuo to give 3-(4-nitroimidazolyl)propylamine as an orange syrup, 2.24 g. The amine, 1.18 g was treated with benzotriazole carboxamidinium 4-methylbenzenesulfonate (2.2 g) and DIEA (1.5 ml) in acetonitrile (8 ml) with shaking at room temperature overnight. Addition of ether gave amino[3-(4-nitroimidazolyl)propyl]carboxamidinium 4-methylbenzenesulfonate as a beige solid.

Workup

temperatureThe mixture was cooled
customcarefully quenched with water
customAt this point the solid product precipitated out

Sources & evidence

ORD record: ord-a0c1ef516d9042b2bd0c5cc315da8127
Source dataset: uspto-grants-2008_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07425557B2

Reaction notes

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