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

HRID 245663노트

반응식

HRID 245663 반응식
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

참가 물질

8

반응물 5

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

생성물 1

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

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
0 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-b39c68585fab4391a995c94debb1682b
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658794B2

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