1-Hydroxybenzotriazole → 3-oxo-N-(6-phenyl-pyridin-3-yl)-3-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-propionamide

HRID 1665641Notes

Reaction equation

HRID 1665641 reaction equation
C1C=CC2N(O)N=NC=2C=1.[O:11]=[C:12]([N:17]1[CH2:22][CH2:21][N:20]([C:23](=[O:34])[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[C:30]([F:33])([F:32])[F:31])[CH2:19][CH2:18]1)[CH2:13][C:14]([OH:16])=O.CCN=C=NCCCN(C)C.Cl.[C:47]1([C:53]2[N:58]=[CH:57][C:56]([NH2:59])=[CH:55][CH:54]=2)[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1>CN(C1C=CN=CC=1)C.CN(C=O)C.O>[O:11]=[C:12]([N:17]1[CH2:18][CH2:19][N:20]([C:23](=[O:34])[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[C:30]([F:33])([F:32])[F:31])[CH2:21][CH2:22]1)[CH2:13][C:14]([NH:59][C:56]1[CH:57]=[N:58][C:53]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)=[CH:54][CH:55]=1)=[O:16]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27628776-Phenylpyridin-3-amineHCID 57875811HCID 57875811, compound

Product 1

HCID 442313303-oxo-N-(6-phenyl-pyridin-3-yl)-3-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-propionamideYield 25%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
10 °C

Procedure

HOBt (48 mg, 0.35 mmol) and DMAP (54 mg, 0.44 mmol) were added to a stirred solution of 3-oxo-3-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-propionic acid (100 mg, 0.29 mmol) in DMF (2 mL). The reaction mixture was cooled to 10° C. and EDCI.HCl (67 mg, 0.35 mmol) followed by 6-phenyl-pyridin-3-ylamine (50 mg, 0.29 mmol) were added. The reaction mixture was stirred at the 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 silica gel 60-120 mesh (60% ethyl acetate in hexane) to afford 36 mg (25%) of 3-oxo-N-(6-phenyl-pyridin-3-yl)-3-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-propionamide. LCMS: 497.16 (M+1)+, 97.8%, 1H NMR: (CDCl3): δ 10.0 (d, 1H), 8.7 (d, 1H), 8.2 (dd, 1H), 8.0 (d, 2H), 7.7 (m, 4H), 7.4 (m, 4H), 4.03 (m, 2H), 3.7 (m, 3H), 3.54 (m, 3H), 3.23 (m. 2H).

Workup

  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

Sources & evidence

ORD record
ord-d639e2ebd1424e0c8ac1480ef23ae5e8
Source dataset
uspto-grants-2011_10
Patent number
US08039463B2

Reaction notes

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