Phosgene → 1-[5-Tert-butyl-3-methylcarbamoyl-2-methoxyphenyl]-3-[4-(4-pyridinyloxy)-naphthalen-1-yl]-urea

HRID 1884601Notes

Reaction equation

HRID 1884601 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[CH:4][CH:3]=1.[C:19](=O)(O)[O-:20].[Na+].C(Cl)(Cl)=O.[C:28]([C:32]1[CH:33]=[C:34]([C:41](=[O:44])[NH:42][CH3:43])[C:35]([O:39][CH3:40])=[C:36]([CH:38]=1)[NH2:37])([CH3:31])([CH3:30])[CH3:29]>ClCCl>[C:28]([C:32]1[CH:33]=[C:34]([C:41](=[O:44])[NH:42][CH3:43])[C:35]([O:39][CH3:40])=[C:36]([NH:37][C:19]([NH:1][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]([O:12][C:13]3[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=3)=[CH:4][CH:3]=2)=[O:20])[CH:38]=1)([CH3:31])([CH3:29])[CH3:30]

Participants

6

Reactant 4

HCID 6371PhosgeneHCID 516892Sodium BicarbonateHCID 235058205-Tert-butyl-2-methoxy-3-methylcarbamoylanilineHCID 235058621-Amino-4-(4-pyridinyl)oxynaphthalene

Product 1

HCID 235058751-[5-Tert-butyl-3-methylcarbamoyl-2-methoxyphenyl]-3-[4-(4-pyridinyloxy)-naphthalen-1-yl]-urea

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

1-Amino-4-(4-pyridinyloxy)naphthalene (Example 6) (1.0 mmol) is dissolved in dichloromethane (15 mL). An equal volume of sat. aqueous sodium bicarbonate is added, and the biphasic solution is cooled to 0° C. During the addition of phosgene (1.93 M in toluene, 1.0 mL), stirring is stopped. Immediately afterward, stirring is resumed for 15 min with the reaction mixture at 0° C. The layers are separated, the organics dried over solid magnesium sulfate and concentrated to approximately 5 mL of solution. 5-tert-Butyl-3-methylcarbamoyl-2-methoxyaniline (Example 3) (0.9 mmol) in dichloromethane (5 mL) is added, and the reaction mixture is stirred overnight at ambient temperature. The solvent is removed by rotary evaporation and the resulting product purified by flash chromatography over silica gel with a suitable elutant such as CH2Cl2:MeOH (95:5) to give the title compound.

Workup

  1. stirringImmediately afterward, stirring
  2. customThe layers are separated
  3. dry with materialthe organics dried over solid magnesium sulfate
  4. concentrationconcentrated to approximately 5 mL of solution
  5. stirringthe reaction mixture is stirred overnight at ambient temperature
  6. customThe solvent is removed by rotary evaporation
  7. customthe resulting product purified by flash chromatography over silica gel with a suitable elutant such as CH2Cl2:MeOH (95:5)

Sources & evidence

ORD record
ord-3b5395b801904d60bfce1a1f418e8012
Source dataset
uspto-grants-2004_07
Patent number
US06765009B2

Reaction notes

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