Dimethylformamide → 2-{2-[7-Chloro-3-(3,5-dimethylphenyl)-6-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-oxo-1,2-dihydroquinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 1858107Notes

Reaction equation

HRID 1858107 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][CH2:15][O:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([Cl:28])=[C:24](I)[CH:25]=2)[NH:20][C:19](=[O:29])[C:18]=1[C:30]1[CH:35]=[C:34]([CH3:36])[CH:33]=[C:32]([CH3:37])[CH:31]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:38](=[N:41][OH:42])([NH2:40])[CH3:39].[CH3:43]N(C)C=O>C(N(CC)CC)C.C(OCC)(=O)C.Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][CH2:15][O:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([Cl:28])=[C:24]([C:43]3[O:42][N:41]=[C:38]([CH3:39])[N:40]=3)[CH:25]=2)[NH:20][C:19](=[O:29])[C:18]=1[C:30]1[CH:35]=[C:34]([CH3:36])[CH:33]=[C:32]([CH3:37])[CH:31]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 6228DimethylformamideHCID 30926N-HydroxyacetamidineHCID 539972552-{2-[7-Chloro-3-(3,5-dimethylphenyl)-6-iodo-2-oxo-1,2-dihydro-quinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 545563852-{2-[7-Chloro-3-(3,5-dimethylphenyl)-6-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-oxo-1,2-dihydroquinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-{2-[7-chloro-3-(3,5-dimethylphenyl)-6-iodo-2-oxo-1,2-dihydro-quinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester (EXAMPLE 4.2 Step B, 200 mg in a mixture of 3 mL dry N,N-dimethylformamide and 0.9 mL triethylamine) was added 118 mg of acetamide oxime followed by 11 mg of dichlorobis(triphenylphosphine) palladium (II) and the mixture heated to reflux on an oil bath under an atmosphere of carbon monoxide. After 12 hours, the mixture was cooled to room temperature and diluted with ethyl acetate and 0.5N hydrochloric acid. This was extracted with ethyl acetate and the organic portion washed with brine then dried over sodium sulfate. Purification of the concentrate by flash chromatography on silica gel (ethyl acetate:hexane, 1:4; then 3:7) gave the title compound (88 mg).

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux on an oil bath under an atmosphere of carbon monoxide
  3. extractionThis was extracted with ethyl acetate
  4. washthe organic portion washed with brine
  5. dry with materialthen dried over sodium sulfate
  6. customPurification of the
  7. concentrationconcentrate by flash chromatography on silica gel (ethyl acetate

Sources & evidence

ORD record
ord-9f115e397f3a4c14aa2840a0676fffa0
Source dataset
uspto-grants-2000_11
Patent number
US06150352

Reaction notes

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