1-Hydroxybenzotriazole → HCID 44235501, compound

HRID 1093584Notes

Reaction equation

HRID 1093584 reaction equation
[C:1]1([C:7]2[O: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.Cl.[Br:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=1[NH:59][CH:60]1[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]1>CN(C=O)C.O>[Br:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=1[NH:59][CH:60]1[CH2:65][CH2:64][N:63]([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)[O:11][N:10]=2)=[O:13])[CH2:62][CH2:61]1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 433543392-[(5-Phenyl-1,2-oxazol-3-yl)formamido]acetic acidHCID 66545672N-(2-Bromophenyl)piperidin-4-amine dihydrochloride

Product 1

HCID 44235501HCID 44235501, compoundYield 22.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of [(5-phenyl-isoxazole-3-carbonyl)-amino]-acetic acid (0.075 g, 0.00027 mol) in DMF (2 mL), was added DIPEA (171.5 mg, 0.00133 mol), HOBt (44.8 mg, 0.00033 mol) and EDCI.HCl (0.064 g, 0.00033 mol) at ambient temperature. After 2 minutes (2-bromo-phenyl)-piperidin-4-yl-amine dihydrochloride (0.078 g, 0.00026 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 washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by column chromatography using basic aluminium oxide (35% ethyl acetate in hexane) to afford 0.028 g (22%) of 5-phenyl-isoxazole-3-carboxylic acid {2-[4-(2-bromo-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide. LCMS: 483.1 (M+1)+, 97.4%, 1H NMR (DMSO-d6): δ 8.6 (t, 1H), 7.85 (m, 2H), 7.6 (m, 3H), 7.4 (m, 2H), 7.2 (t, 1H), 6.85 (d, 1H), 6.55 (t, 1H), 4.7 (d, 1H), 4.3 (d, 1H), 4.2 (d, 2H), 3.9 (d, 1H), 3.6 (m, 1H), 3.2 (m, 1H), 2.8 (m, 1H), 2.0 (t, 2H), 1.4 (m, 2H).

Workup

  1. extractionthe product was extracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with brine solution
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by column chromatography

Sources & evidence

ORD record
ord-99d68348f5d147a3a284ab00c3febb7a
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

Loading…