Pyridine → 2-{2-[3-(3-Bromophenyl)-7-chloro-6-(3-cyclopropyl-ureido)-2-oxo-1,2-dihydroquinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 1857618Notes

Reaction equation

HRID 1857618 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]([NH2:27])[CH:25]=2)[NH:20][C:19](=[O:29])[C:18]=1[C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([Br:36])[CH:31]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:37]1[CH:42]=C[CH:40]=[CH:39][CH:38]=1.ClC(Cl)([O:46]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][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]([NH:27][C:42]([NH:37][CH:38]3[CH2:40][CH2:39]3)=[O:46])[CH:25]=2)[NH:20][C:19](=[O:29])[C:18]=1[C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([Br:36])[CH:31]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 1049PyridineHCID 69828CyclopropylamineHCID 94429TriphosgeneHCID 541646722-{2-[6-Amino-3-(3-bromophenyl)-7-chloro-2-oxo-1,2-dihydroquinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 539044082-{2-[3-(3-Bromophenyl)-7-chloro-6-(3-cyclopropyl-ureido)-2-oxo-1,2-dihydroquinolin-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 2-{2-[6-amino-3-(3-bromophenyl)-7-chloro-2-oxo-1,2-dihydroquinolin-4-yloxy]-1-ethyl}-piperidine-1-carboxylic acid tert-butyl ester (20 mg in 1.0 mL methylene chloride) at 0° C. was added 0.009 mL pyridine followed by 4 mg triphosgene and the mixture allowed to stir at 0° C. for 1 hour. At this time 0.012 mL of cyclopropylamine was added via syringe and the reaction mixture warmed to room temperature. After 2 hours, the mixture was diluted with 20 mL ethyl acetate and washed with saturated ammonium chloride (10 mL) and brine (10 mL). The organic portion was dried over magnesium sulfate then concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (hexane:ethyl acetate, 2:1; then 1:1; then 0:1) to give the title compound (14 mg).

Workup

  1. temperaturethe reaction mixture warmed to room temperature
  2. waitAfter 2 hours
  3. washwashed with saturated ammonium chloride (10 mL) and brine (10 mL)
  4. dry with materialThe organic portion was dried over magnesium sulfate
  5. concentrationthen concentrated in vacuo
  6. customThe crude product was purified by flash chromatography on silica gel (hexane

Sources & evidence

ORD record
ord-91f094319816460da755ca68ef4b0d9c
Source dataset
uspto-grants-2000_11
Patent number
US06147088

Reaction notes

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