1-Hydroxybenzotriazole → 3-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-3-oxo-N-(6-phenyl-pyridin-3-yl)-propionamide

HRID 1093683

반응식

HRID 1093683 반응식
[Cl:1][C:2]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11](=[O:16])[CH2:12][C:13]([OH:15])=O)[CH2:7][CH2:6]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[C:44]1([C:50]2[N:55]=[CH:54][C:53]([NH2:56])=[CH:52][CH:51]=2)[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>CN(C=O)C.CN(C1C=CN=CC=1)C.O>[Cl:1][C:2]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:3]=1[O:4][CH:5]1[CH2:6][CH2:7][N:8]([C:11](=[O:16])[CH2:12][C:13]([NH:56][C:53]2[CH:54]=[N:55][C:50]([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)=[CH:51][CH:52]=2)=[O:15])[CH2:9][CH2:10]1

참가 물질

8

반응물 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27628776-Phenylpyridin-3-amineHCID 578744413-[4-(2-Chloro-5-fluoro-phenoxy)-piperidin-1-yl]-3-oxo-propionic acid

생성물 1

HCID 578744953-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-3-oxo-N-(6-phenyl-pyridin-3-yl)-propionamide수율 19%

시약·촉매·용매 3

HCID 142844-(Dimethylamino)pyridine촉매HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

To a stirred solution of 3-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-3-oxo-propionic acid (0.1 g, 0.00032 mole) in DMF (5 mL) was added DMAP (0.059 g, 0.00048 mole), HOBt (0.051 g, 0.00038 mole) and EDCI.HCl (0.073 g, 0.00038 mole). After 2 minutes 6-phenyl-pyridin-3-ylamine (0.06 g, 0.00035 mole) was added and the resulting mixture was stirred overnight. The reaction mixture was then diluted with cold water and the product was extracted with ethyl acetate. The organic layers were dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by column chromatography using silica gel 60-120 mesh (50% ethyl acetate in hexane) to afford 0.026 g (19%) of 3-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-3-oxo-N-(6-phenyl-pyridin-3-yl)-propionamide. LC-MS purity: 468 (M+1)+, 93.7%, 1H NMR (CDCl3): δ 10.5 (s, 1H), 8.8 (s, 1H), 8.3 (d, 1H), 8.0 (d, 2H), 7.7 (d, 1H), 7.4 (m, 4H), 6.7 (m, 2H), 4.7 (m, 1H), 4.2 (m, 1H), 3.8 (m, 1H), 3.7 (m, 2H), 3.55 (s, 2H), 2.0 (m, 4H).

후처리

  1. extractionthe product was extracted with ethyl acetate
  2. dry with materialThe organic layers were dried over sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe resulting residue was purified by column chromatography

출처 및 근거

ORD 기록
ord-a839eac87abe457f900b4ef8fd86d3a1
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08129376B2

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