Phosgene → HCID 15434719, compound

HRID 1737236Notes

Reaction equation

HRID 1737236 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2([N:15]3[CH2:20][CH2:19][N:18]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[CH2:17][CH2:16]3)[CH2:13][CH2:12][CH:11]([CH3:14])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[C:34](Cl)(Cl)=[O:35].[NH2:38][C:39]1[CH:40]=[C:41]2[C:46](=[CH:47][CH:48]=1)[N:45]=[CH:44][CH:43]=[CH:42]2>C(Cl)Cl.CO.C(Cl)Cl>[CH3:14][CH:11]1[CH2:12][CH2:13][C:8]([C:4]2[CH:3]=[C:2]([NH:1][C:34]([NH:38][C:39]3[CH:40]=[C:41]4[C:46](=[CH:47][CH:48]=3)[N:45]=[CH:44][CH:43]=[CH:42]4)=[O:35])[CH:7]=[CH:6][CH:5]=2)([N:15]2[CH2:16][CH2:17][N:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH2:19][CH2:20]2)[CH2:9][CH2:10]1

Participants

7

Reactant 4

HCID 6371PhosgeneHCID 8471TriethylamineHCID 113736-AminoquinolineHCID 15434718HCID 15434718, compound

Product 1

HCID 15434719HCID 15434719, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 1-(3-aminophenyl)-1-(4-phenylpiperazin-1-yl)-4-methyl-cyclohexane (cis isomer, 116 mg, 0.332 mmol) and triethylamine (116 μL, 0.83 mmol) in dry CH2Cl2 (7 mL) was brought to 0° C. using an ice bath. Phosgene (1.93 M in toluene, 181 μL) was added dropwise and the resulting mixture was stirred at 0° C., under a dry N2 atmosphere, for 30 minutes. 6-aminoquinoline (53 mg, 0.365 mmol) was added as a solid and the reaction was allowed to come to room temperature. The reaction was stirred overnight, diluted with an equal volume of CH2Cl2, washed with H2O, dried (Na2SO4) and concentrated to give the crude urea. Silica gel chromatography (eluent: 5% CH3OH/CH2Cl2) yielded pure N-[3-[4-methyl-1-(4-phenyl-1-piperazinyl)cyclohexyl]phenyl]-N'-6-quinolinyl-urea (cis isomer) as an off-white solid. The HCI salt was prepared by adding excess saturated EtOAc/HCI solution to the free base in dry MeOH. Concentration of the homogeneous solution yielded a white solid which was washed with EtOAc. m=185-187° C.

Workup

  1. customwas brought to 0° C.
  2. customto come to room temperature
  3. stirringThe reaction was stirred overnight
  4. washwashed with H2O
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customto give the crude urea

Sources & evidence

ORD record
ord-af88de6c906a405f8ed460f63b234e76
Source dataset
uspto-grants-1999_10
Patent number
US05962455

Reaction notes

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