1-Hydroxybenzotriazole → HCID 66591343, compound

HRID 1093678Notes

Reaction equation

HRID 1093678 reaction equation
[C:1]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:6]=[CH:5][C:4]([NH:7][C:8](=[O:13])[CH2:9][C:10]([OH:12])=O)=[CH:3][CH:2]=1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.Cl.Cl.[F:52][C:53]1[CH:65]=[CH:64][C:63]([F:66])=[CH:62][C:54]=1[O:55][CH:56]1[CH2:61][CH2:60][NH:59][CH2:58][CH2:57]1>CN(C=O)C.O>[C:1]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:2]=[CH:3][C:4]([NH:7][C:8](=[O:13])[CH2:9][C:10]([N:59]2[CH2:58][CH2:57][CH:56]([O:55][C:54]3[CH:62]=[C:63]([F:66])[CH:64]=[CH:65][C:53]=3[F:52])[CH2:61][CH2:60]2)=[O:12])=[CH:5][CH:6]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 55049154N-biphenyl-4-yl-malonamic acidHCID 665915534-(2,5-Difluoro-phenoxy)-piperidine hydrochloride

Product 1

HCID 66591343HCID 66591343, compoundYield 22.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
10 °C

Procedure

To a stirred solution of N-biphenyl-4-yl-malonamic acid (0.075 g, 0.0003 mole) in DMF (2 mL) was added, HOBt (0.06 g, 0.00045 mole) and DIPEA (0.135 g, 0.001 mole). The mixture was then cooled to 10° C. and EDCI.HCl (0.086 g, 0.00045 mole) followed by 4-(2,5-difluoro-phenoxy)-piperidine hydrochloride (0.073 g, 0.0003 mole) were added. 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 layer was dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by column chromatography using neutral aluminium oxide (5% methanol in chloroform) to afford 0.03 g (22%) of N-biphenyl-4-yl-3-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-3-oxo-propionamide. LC-MS purity: 451.18 (M+1)+, 90.58%, 1H NMR (DMSO-d6): δ 10.2 (s, 1H), 7.7 (m, 6H), 7.4 (m, 2H), 7.2 (m, 2H), 6.8 (m, 1H), 4.7 (m, 1H), 3.9 (m, 1H), 3.8 (m, 1H), 3.6 (s, 2H), 3.4 (m, 1H), 2.0 (m, 2H), 1.7 (m, 1H), 1.6 (m, 1H).

Workup

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

Sources & evidence

ORD record
ord-32a4b1ea9d9c48fdb5bbf71537e9250a
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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