Toluene → 3-(2,6-Dichloro-3,5-dimethoxyphenyl)-1-(6-((4-(2-methoxyethoxy)-2-nitrophenyl)amino)pyrimidin-4-yl)-1-methylurea

HRID 58179Notes

Reaction equation

HRID 58179 reaction equation
[Cl:1][C:2]1[C:8]([O:9][CH3:10])=[CH:7][C:6]([O:11][CH3:12])=[C:5]([Cl:13])[C:3]=1[NH2:4].[C:14](Cl)(Cl)=[O:15].C1(C)C=CC=CC=1.[CH3:25][O:26][CH2:27][CH2:28][O:29][C:30]1[CH:35]=[CH:34][C:33]([NH:36][C:37]2[CH:42]=[C:41]([NH:43][CH3:44])[N:40]=[CH:39][N:38]=2)=[C:32]([N+:45]([O-:47])=[O:46])[CH:31]=1>O1CCOCC1.CCOC(C)=O>[Cl:1][C:2]1[C:8]([O:9][CH3:10])=[CH:7][C:6]([O:11][CH3:12])=[C:5]([Cl:13])[C:3]=1[NH:4][C:14](=[O:15])[N:43]([C:41]1[CH:42]=[C:37]([NH:36][C:33]2[CH:34]=[CH:35][C:30]([O:29][CH2:28][CH2:27][O:26][CH3:25])=[CH:31][C:32]=2[N+:45]([O-:47])=[O:46])[N:38]=[CH:39][N:40]=1)[CH3:44]

Participants

7

Reactant 4

HCID 1140TolueneHCID 6371PhosgeneHCID 594862532,6-Dichloro-3,5-dimethoxyanilineHCID 118024469HCID 118024469, compound

Product 1

HCID 1180258423-(2,6-Dichloro-3,5-dimethoxyphenyl)-1-(6-((4-(2-methoxyethoxy)-2-nitrophenyl)amino)pyrimidin-4-yl)-1-methylureaYield 32%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of 2,6-dichloro-3,5-dimethoxyaniline (500 g, 2.252 mmol) in dioxane (10 mL) was added 20% phosgene in toluene (4.4 mL, 9.0 mmol) under argon atmosphere at 0° C. The resulting mixture was stirred for 6 h at 90° C., and then allowed to cool to room temperature. The solvents were removed and the residue was dissolved in toluene (10 mL). To this, was added N4-(4-(2-methoxyethoxy)-2-nitrophenyl)-N6-methylpyrimidine-4,6-diamine (0.718 g, 8.358 mmol, 1.0 eq). The resultant reaction mixture was then refluxed for 6 h. After completion of the reaction by TLC (Hexanes:EtOAc, 7:3), reaction mixture was cooled to room temperature, concentrated under vacuum to obtain a crude reaction mixture. The solid precipitated on addition of ethyl acetate to the crude reaction mixture was filtered, washed with ether and pentane to afford the title compound (0.285, yield: 32%) as a white solid. MS (ESI): 567.0 [M+H]+.

Workup

  1. temperatureto cool to room temperature
  2. customThe solvents were removed
  3. dissolutionthe residue was dissolved in toluene (10 mL)
  4. customThe resultant reaction mixture
  5. temperaturewas then refluxed for 6 h
  6. customAfter completion of the reaction
  7. temperaturewas cooled to room temperature
  8. concentrationconcentrated under vacuum
  9. customto obtain a crude
  10. customreaction mixture
  11. customThe solid precipitated on addition of ethyl acetate to the crude
  12. customreaction mixture
  13. filtrationwas filtered
  14. washwashed with ether and pentane

Sources & evidence

ORD record
ord-ae15bbbf396b42b9a65e7300f5277008
Source dataset
uspto-grants-2016_09
Patent number
US09434697B2

Reaction notes

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