Triethylamine → 5,6-dichloro-N-methyl-N-(2-pyrrolidin-1-ylethyl)nicotinamide

HRID 81676

Reaction equation

S(Cl)(Cl)=O.[Cl:5][C:6]1[C:7]([Cl:15])=[N:8][CH:9]=[C:10]([CH:14]=1)[C:11]([OH:13])=O.C(N(CC)CC)C.[CH3:23][NH:24][CH2:25][CH2:26][N:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1>C(Cl)(Cl)Cl.O.O1CCCC1>[Cl:5][C:6]1[C:7]([Cl:15])=[N:8][CH:9]=[C:10]([CH:14]=1)[C:11]([N:24]([CH3:23])[CH2:25][CH2:26][N:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1)=[O:13]

Participants

Conditions

Temperature: 90 °C

Procedure

Thionyl chloride (6 ml) was added to 5,6-dichloronicotinic acid (600 mg, 3.13 mmol), and stirred under a nitrogen atmosphere at 90° C. for 30 minutes. The reaction solution was concentrated under reduced pressure, and with cooling with ice, triethylamine (1.31 ml, 9.38 mmol) and N-methyl-2-pyrrolidin-1-ylethanamine (481 mg, 3.75 mmol) were added to a tetrahydrofuran solution (4 ml) of the obtained residue, and stirred at room temperature for 3 minutes. Saturated saline water and chloroform were added to the reaction solution, the organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by amine-type silica gel column chromatography (Biotage NH, hexane:ethyl acetate=4:1 to 1:1) to obtain 5,6-dichloro-N-methyl-N-(2-pyrrolidin-1-ylethyl)nicotinamide 967 mg) as an orange oil.

Workup

concentrationThe reaction solution was concentrated under reduced pressure
stirringstirred at room temperature for 3 minutes
dry with materialthe organic layer was dried over anhydrous sodium sulfate
concentrationconcentrated under reduced pressure
customThe obtained residue was purified by amine-type silica gel column chromatography (Biotage NH, hexane:ethyl acetate=4:1 to 1:1)

Sources & evidence

ORD record: ord-b7936fa6667c445584f1ffe69e8e3eb8
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846700B2

Linked notes

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