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

HRID 1093683

反応式

HRID 1093683 の反応式
[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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-a839eac87abe457f900b4ef8fd86d3a1
出典データセット
uspto-grants-2012_03
特許番号
US08129376B2

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