Triethylamine → N-((3-chloropyrazin-2-yl)methyl)azetidine-1-carboxamide

HRID 245663ノート

反応式

HRID 245663 の反応式
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]=1

参加物

8

反応物 5

HCID 8471TriethylamineHCID 10422AzetidineHCID 10426DiphosgeneHCID 81531DiisopropylethylamineHCID 42614233(3-Chloropyrazin-2-yl)methanamine hydrochloride

生成物 1

HCID 86674633N-((3-chloropyrazin-2-yl)methyl)azetidine-1-carboxamide収率 62.8%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

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.

後処理

  1. customwere removed by filtration
  2. concentrationthe filtrate was concentrated at 50 mbar (50° C. bath temperature)
  3. stirringthe reaction mixture was stirred for three hours
  4. customThe solids were removed by filtration
  5. concentrationthe filtrate was concentrated in vacuo
  6. customPurification

出典と根拠

ORDレコード
ord-b39c68585fab4391a995c94debb1682b
出典データセット
uspto-grants-2014_02
特許番号
US08658794B2

反応ノート

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