Pyridine → (S)-2-{2-[7-chloro-6-(3-cyclopropylureido)-3-(3,5-dimethylphenyl)-2-oxo-1,2-dihydro-quinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 1857611Notes

Reaction equation

HRID 1857611 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:14][CH2:15][O:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([Cl:28])=[C:24]([NH2:27])[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].[N:38]1[CH:43]=C[CH:41]=[CH:40][CH:39]=1.ClC(Cl)([O:47]C(=O)OC(Cl)(Cl)Cl)Cl.C1(N)CC1>C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:14][CH2:15][O:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([Cl:28])=[C:24]([NH:27][C:43]([NH:38][CH:39]3[CH2:41][CH2:40]3)=[O:47])[CH:25]=2)[NH:20][C:19](=[O:29])[C:18]=1[C:30]1[CH:31]=[C:32]([CH3:37])[CH:33]=[C:34]([CH3:36])[CH:35]=1)=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

6

Reactant 4

HCID 1049PyridineHCID 69828CyclopropylamineHCID 94429TriphosgeneHCID 54025519(S)-2-{2-[6-amino-7-chloro-3-(3,5-dimethylphenyl)-2-oxo-1,2-dihydro-quinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 53968811(S)-2-{2-[7-chloro-6-(3-cyclopropylureido)-3-(3,5-dimethylphenyl)-2-oxo-1,2-dihydro-quinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (S)-2-{2-[6-amino-7-chloro-3-(3,5-dimethylphenyl)-2-oxo-1,2-dihydro-quinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester (700 mg in 13 mL dry methylene chloride) at 0° C. was added 0.33 mL pyridine followed by 158 mg triphosgene and the mixture allowed to stir at 0° C. for 1 hour. At this time 0.46 mL of cyclopropylamine was added via syringe and the reaction mixture warmed to room temperature. After 2 hours, the mixture was diluted with 200 mL ethyl acetate and washed with saturated ammonium chloride (100 mL) and brine (100 mL). The organic portion was dried over magnesium sulfate then concentrated in vacuo. The crude product was purified by crystallization from ethyl acetate to give the title compound (615 mg).

Workup

  1. temperaturethe reaction mixture warmed to room temperature
  2. waitAfter 2 hours
  3. washwashed with saturated ammonium chloride (100 mL) and brine (100 mL)
  4. dry with materialThe organic portion was dried over magnesium sulfate
  5. concentrationthen concentrated in vacuo
  6. customThe crude product was purified by crystallization from ethyl acetate

Sources & evidence

ORD record
ord-3ed13c4149764a9db3446166698215fe
Source dataset
uspto-grants-2000_11
Patent number
US06147088

Reaction notes

Loading…