Triethylamine → HCID 72551665, compound

HRID 749025Notes

Reaction equation

HRID 749025 reaction equation
[CH3:1][N:2]([CH3:35])[C:3]([CH:5]([NH:24][S:25]([C:28]1[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=1)(=[O:27])=[O:26])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][C:21](O)=[O:22])=[CH:15][CH:14]=2)=[CH:9][CH:8]=1)=[O:4].ON1[C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C.Cl.C([O:73][NH2:74])C1C=CC=CC=1>CN(C=O)C.CCCCCC.C(OCC)(=O)C>[CH3:1][N:2]([CH3:35])[C:3](=[O:4])[CH:5]([NH:24][S:25]([C:28]1[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=1)(=[O:26])=[O:27])[CH2:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]2[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][C:21](=[O:22])[NH:74][O:73][C:40]3[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=3)=[CH:15][CH:14]=2)=[CH:11][CH:12]=1

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 102312Benzyloxyamine hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 15982714HCID 15982714, compound2×

Product 1

HCID 72551665HCID 72551665, compoundYield 64.5%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
2.5 °C

Procedure

The compound 3-{4′-[2-dimethylcarbamoyl-2-(toluene-4-sulfonylamino)-ethyl]-biphenyl-4-yl}-propionic acid, 55 (1.05 g, 2.1 mmol) was dissolved in dry DMF (20 mL) and cooled to 0-5° C. 1-Hydroxybenzotriazole (0.32 g, 2.34 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.41 g, 2.13 mmol), and triethylamine (0.9 mL, 6.37 mmol) were added to the above mixture followed by stirring for 15 min. O-Benzylhydroxylamine hydrochloride (0.37 g, 2.34 mmol) was added and the mixture was allowed to come to room temperature and stirred for 18 h. The solvent was evaporated under reduced pressure and the residual oil was taken up in CHCl3 (50 mL). The organic layer was extracted with 2.0 M HCl (1×10 mL), saturated NaHCO3 (1×10 mL), and brine (1×25 mL). The resulting CHCl3 layer was dried and concentrated to yield the crude product. Flash chromatography (30-70% ethyl acetate in hexane containing 1% acetic acid) yielded the desired benzyl hydroxamate 56 (0.8 g, 64.5%). 1H NMR (400 MHz, DMSO-d6): 10.97 (s, 1H), 8.09 (d, J=8.4 Hz, 1H), 7.55 (d, J=8.4 Hz, 2H), 7.51 (d, J=8.0 Hz, 2H), 7.49 (d, J=8.4 Hz, 2H), 7.30-7.35 (m, 5H), 7.27 (d, J=8.4 Hz, 2H), 7.24 (d, J=8.4 Hz, 2H), 7.18 (d, J=8.4 Hz, 2H), 4.73 (s, 2H), 4.33 (m, 1H), 2.81-2.89 (m, 3H), 2.74 (s, 3H), 2.64 (dd, J=14.0 and 8.0 Hz, 1H), 2.53 (s, 3H), 2.29 (t, J=7.6 Hz, 2H), 2.27 (s, 3H).

Workup

  1. customto come to room temperature
  2. stirringstirred for 18 h
  3. customThe solvent was evaporated under reduced pressure
  4. extractionThe organic layer was extracted with 2.0 M HCl (1×10 mL), saturated NaHCO3 (1×10 mL), and brine (1×25 mL)
  5. dry with materialThe resulting CHCl3 layer was dried
  6. concentrationconcentrated
  7. customto yield the crude product

Sources & evidence

ORD record
ord-993f90911a314789bed460a99494f623
Source dataset
uspto-grants-2008_07
Patent number
US07399786B2

Reaction notes

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