Phosgene → 2-{2-[7-Chloro-3-(3,5-dimethylphenyl)-6-(3-ethylureido)-2-oxo-1,2-dihydroquinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid benzyl ester

HRID 1857600Notes

Reaction equation

HRID 1857600 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH:12]1[CH2:17][CH2:18][O:19][C:20]1[C:29]2[C:24](=[CH:25][C:26]([Cl:31])=[C:27]([NH2:30])[CH:28]=2)[NH:23][C:22](=[O:32])[C:21]=1[C:33]1[CH:38]=[C:37]([CH3:39])[CH:36]=[C:35]([CH3:40])[CH:34]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:41](Cl)(Cl)=[O:42].[CH2:45]([N:47](CC)CC)[CH3:46].Cl.C(N)C>C(Cl)Cl.C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH:12]1[CH2:17][CH2:18][O:19][C:20]1[C:29]2[C:24](=[CH:25][C:26]([Cl:31])=[C:27]([NH:30][C:41]([NH:47][CH2:45][CH3:46])=[O:42])[CH:28]=2)[NH:23][C:22](=[O:32])[C:21]=1[C:33]1[CH:38]=[C:37]([CH3:39])[CH:36]=[C:35]([CH3:40])[CH:34]=1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 6371PhosgeneHCID 8471Triethylamine2×HCID 11198Ethylamine hydrochlorideHCID 539323332-{2-[6-Amino-7-chloro-3-(3,5-dimethylphenyl)-2-oxo-1,2-dihydroquinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid benzyl ester

Product 1

HCID 538466182-{2-[7-Chloro-3-(3,5-dimethylphenyl)-6-(3-ethylureido)-2-oxo-1,2-dihydroquinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid benzyl ester

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-{2-[6-amino-7-chloro-3-(3,5-dimethylphenyl)-2-oxo-1,2-dihydroquinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid benzyl ester (prepared essentially as described in Example 6, 158 mg in 4 mL dry methylene chloride) at 0° C. was added phosgene (0.22 mL of a 1.93 M solution in toluene) followed by 0.081 mL of triethylamine and the mixture stirred for 1 hour at 0° C. At this time, 114.5 mg of ethylamine hydrochloride was added followed by additional triethylamine (0.195 mL) and the mixture allowed to warm to room temperature. After 20 hours, the mixture was diluted with ethyl acetate (200 mL) and the reaction quenched by the addition of water. The organic portion was washed sequentially with saturated sodium bicarbonate and brine. The solvent was removed in vacuo to provide the crude title compound (187 mg).

Workup

  1. customat 0° C.
  2. temperatureto warm to room temperature
  3. waitAfter 20 hours
  4. customthe reaction quenched by the addition of water
  5. washThe organic portion was washed sequentially with saturated sodium bicarbonate and brine
  6. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-5ec943f57d2c4e8199bad562a26ea036
Source dataset
uspto-grants-2000_11
Patent number
US06147088

Reaction notes

Loading…