1-Hydroxybenzotriazole → 3-[4-(2-Bromo-benzoyl)-piperazin-1-yl]-3-oxo-propionic acid tert-butyl ester

HRID 1665654노트

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HRID 1665654 반응식
C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[C:20]([O:24][C:25]([CH2:27][C:28]([O-:30])=O)=[O:26])([CH3:23])([CH3:22])[CH3:21].[Li+].CCN=C=NCCCN(C)C.Cl.Cl.[Br:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=1[C:52]([N:54]1[CH2:59][CH2:58][NH:57][CH2:56][CH2:55]1)=[O:53]>CN(C=O)C.O>[C:20]([O:24][C:25](=[O:26])[CH2:27][C:28]([N:57]1[CH2:56][CH2:55][N:54]([C:52](=[O:53])[C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][C:46]=2[Br:45])[CH2:59][CH2:58]1)=[O:30])([CH3:21])([CH3:22])[CH3:23]

참가 물질

8

반응물 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66625832(2-Bromo-phenyl)-piperazin-1-yl-methanone hydrochlorideHCID 86634609Lithium tert-butoxycarbonyl-acetate

생성물 1

HCID 578757933-[4-(2-Bromo-benzoyl)-piperazin-1-yl]-3-oxo-propionic acid tert-butyl ester수율 35.8%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
10 °C

실험 절차

HOBt (585 mg, 4.3 mmol) and DIEA (933 mg, 7.2 mmol) were added to a stirred solution of lithium tert-butoxycarbonyl-acetate (600 mg, 3.6 mmol) in DMF (6 mL). The reaction mixture was cooled to 10° C. and EDCI.HCl (830 mg, 4.3 mmol) followed by (2-bromo-phenyl)-piperazin-1-yl-methanone hydrochloride (1.3 g, 4.3 mmol) were added. The reaction mixture was stirred at room temperature overnight then diluted with water and the product extracted with ethyl acetate. The organic layer was washed with brine solution, dried over Na2SO4 and concentrated. The residue was purified by column chromatography using neutral alumina (3% methanol in chloroform) to afford 530 mg (31%) of 3-[4-(2-bromo-benzoyl)-piperazin-1-yl]-3-oxo-propionic acid tert-butyl ester. LCMS: 412.08 (M+)+, 52.6%, 1H NMR: (DMSO-d6): δ 7.7 (d, 1H), 7.5 (m, 1H), 7.4 (m, 2H), 3.7-3.4 (m, 8H), 3.2-3.1 (m, 2H), 1.4 (s, 9H).

후처리

  1. additionwere added
  2. extractionthe product extracted with ethyl acetate
  3. washThe organic layer was washed with brine solution
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography

출처 및 근거

ORD 기록
ord-6c4b7b86438b43648433454512934082
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08039463B2

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