Triethylamine → N-((3-chloropyrazin-2-yl)methyl)azetidine-1-carboxamide
Reaction equation
Cl[C:2](OC(Cl)(Cl)Cl)=[O:3].[NH:9]1[CH2:12][CH2:11][CH2:10]1.C(N(CC)C(C)C)(C)C.Cl.[NH2:23][CH2:24][C:25]1[C:30]([Cl:31])=[N:29][CH:28]=[CH:27][N:26]=1.C(N(CC)CC)C>O1CCCC1.ClCCl>[Cl:31][C:30]1[C:25]([CH2:24][NH:23][C:2]([N:9]2[CH2:12][CH2:11][CH2:10]2)=[O:3])=[N:26][CH:27]=[CH:28][N:29]=1Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 0 °C
Procedure
A stirred solution of trichloromethyl chloroformate (105 mmol, 12.68 mL) in tetrahydrofuran (100 mL) was cooled to 0° C. and a solution of azetidine (88 mmol, 5 g) and N,N-diisopropylethylamine (193 mmol, 33.6 mL) in tetrahydrofuran (100 mL) was added slowly in 25 minutes. After stirring at 0° C. for one hour the solids were removed by filtration and the filtrate was concentrated at 50 mbar (50° C. bath temperature). The residue was added to a solution of 2-aminomethyl-3-chloropyrazine hydrochloride (66.7 mmol, 12 g) and triethylamine (200 mmol, 27.9 mL) in dichloromethane (200 mL) and the reaction mixture was stirred for three hours. The solids were removed by filtration and the filtrate was concentrated in vacuo. Purification using column chromatography (silica gel; gradient dichloromethane/methanol 100:0 to 95:5) yielded 9.5 g of N-((3-chloropyrazin-2-yl)methyl)azetidine-1-carboxamide.
Workup
- customwere removed by filtration
- concentrationthe filtrate was concentrated at 50 mbar (50° C. bath temperature)
- stirringthe reaction mixture was stirred for three hours
- customThe solids were removed by filtration
- concentrationthe filtrate was concentrated in vacuo
- customPurification
Sources & evidence
- ORD record
- ord-b39c68585fab4391a995c94debb1682b
- Source dataset
- uspto-grants-2014_02
- Patent number
- US08658794B2
Reaction notes
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