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

HRID 1093683Notes

Reaction equation

HRID 1093683 reaction equation
[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

Participants

8

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-a839eac87abe457f900b4ef8fd86d3a1
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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