1-Hydroxybenzotriazole → 5-phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide

HRID 1093614Notes

Reaction equation

HRID 1093614 reaction equation
[C:1]1([C:7]2[NH:11][N:10]=[C:9]([C:12]([NH:14][CH2:15][C:16]([OH:18])=O)=[O:13])[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[F:51][C:52]1[CH:64]=[CH:63][C:62]([F:65])=[CH:61][C:53]=1[O:54][CH:55]1[CH2:60][CH2:59][NH:58][CH2:57][CH2:56]1>CN(C=O)C.O>[F:51][C:52]1[CH:64]=[CH:63][C:62]([F:65])=[CH:61][C:53]=1[O:54][CH:55]1[CH2:56][CH2:57][N:58]([C:16](=[O:18])[CH2:15][NH:14][C:12]([C:9]2[CH:8]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[NH:11][N:10]=2)=[O:13])[CH2:59][CH2:60]1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665915534-(2,5-Difluoro-phenoxy)-piperidine hydrochlorideHCID 178525878HCID 178525878, compound

Product 1

HCID 1785235215-phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amideYield 49.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of [(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetic acid (0.075 g, 0.0003 mol) in DMF (2 mL) was added DIPEA (0.135 g, 0.0012 mol), HOBt (0.061 g, 0.00045 mol) and EDCI.HCl (0.086 g, 0.00045 mol) at ambient temperature. After 2 minutes, 4-(2,5-difluoro-phenoxy)-piperidine hydrochloride (0.076 g, 0.0003 mol) 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 ethyl acetate layer was collected and washed with brine solution, dried over sodium sulfate and concentrated. The resulting residue was purified by column chromatography using neutral aluminum oxide (5% methanol in chloroform) to afford 0.065 g (49%) of 5-phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LCMS: 441.17 (M+1)+, 91.07%, 1H NMR (DMSO-d6): δ 13.8 (bs, 1H), 8.0 (bs, 1H), 7.8 (m, 2H), 7.4 (m, 5H), 7.2 (m, 1H), 6.8 (m, 1H), 4.6 (m, 1H), 4.2 (m, 2H), 3.9 (m, 1H), 3.8 (m, 1H), 2.0 (m, 2H), 1.6 (m, 2H).

Workup

  1. extractionthe product was extracted with ethyl acetate
  2. customThe ethyl acetate layer was collected
  3. washwashed with brine solution
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe resulting residue was purified by column chromatography

Sources & evidence

ORD record
ord-e22eacc0019d430bbb6972a004b24631
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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