Phosgene → HCID 15434720, compound

HRID 1737237Notes

Reaction equation

HRID 1737237 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].[F:38][C:39]1[CH:40]=[C:41]([CH:43]=[CH:44][CH:45]=1)[NH2:42]>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:42][C:41]3[CH:43]=[CH:44][CH:45]=[C:39]([F:38])[CH:40]=3)=[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

6

Reactant 4

HCID 6371PhosgeneHCID 8471TriethylamineHCID 97423-FluoroanilineHCID 15434718HCID 15434718, compound

Product 1

HCID 15434720HCID 15434720, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 1-(3-aminophenyl)-1-(4-phenylpiperazin-1-yl)-4-methyl-cyclohexane (cis isomer, 205 mg, 0.587 mmol) and triethylamine (205 μL, 1.47 mmol) in dry CH2Cl2 (15 mL) was brought to 0° C. using an ice bath. Phosgene (1.93 M in toluene, 365 μL) was added dropwise and the resulting mixture was stirred at 0° C., under a dry N2 atmosphere, for 30 minutes. 3-fluoroaniline (68 μl, 0.705 mmol) was added via syringe and the reaction was allowed to come to room temperature. After 3 h the mixture was diluted with an equal volume of CH2Cl2, washed with H2O, dried (Na2SO4) and concentrated to give the crude urea. The residue was triturated with ether and the resulting solid collected on a sintered glass funnel and washed with ether. Preparative plate chromatography (50% EtOAc/hexanes) afforded pure N-[3-[4-methyl-1-(4-phenyl-1 piperazinyl)cyclohexyl]phenyl]-N'-3-fluorophenyl-urea (cis isomer) as an off-white solid. The HCl salt was prepared by adding excess saturated EtOAc/HCl solution to the free base in dry MeOH. Concentration of the homogeneous solution yielded a solid which was washed with EtOAc and dried under vacuum. mp=149-151° C.

Workup

  1. customwas brought to 0° C.
  2. customto come to room temperature
  3. washwashed with H2O
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customto give the crude urea
  7. customThe residue was triturated with ether
  8. customthe resulting solid collected on a sintered glass funnel
  9. washwashed with ether

Sources & evidence

ORD record
ord-5161381bffca44e99c4c9261eb12c9c1
Source dataset
uspto-grants-1999_10
Patent number
US05962455

Reaction notes

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