Phenyl isocyanate → (+/-)-1-[1-(2-Chloro-pyrimidin-5-yl)-ethyl]-1-(2-fluoro-4-methoxy-phenyl)-3-phenyl-urea

HRID 2216972Notes

Reaction equation

HRID 2216972 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([CH:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=2[F:20])[CH3:10])=[CH:4][N:3]=1.[C:21]1([N:27]=[C:28]=[O:29])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH:9]([N:11]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=2[F:20])[C:28]([NH:27][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:29])[CH3:10])=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 7672Phenyl isocyanateHCID 10358358(+/-)-[1-(2,4-Dichloro-pyrimidin-5-yl)-ethyl]-(2-fluoro-4-methoxy-phenyl)-amine

Product 1

HCID 21946011(+/-)-1-[1-(2-Chloro-pyrimidin-5-yl)-ethyl]-1-(2-fluoro-4-methoxy-phenyl)-3-phenyl-urea

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

(±)-[1-(2,4-Dichloro-pyrimidin-5-yl)-ethyl]-(2-fluoro-4-methoxy-phenyl)-amine (0.45 g; 1.41 mmol) (from Example 8b supra) and phenyl isocyanate (165 μL; 1.52 mmol) (Aldrich) were combined in toluene (5 mL) and heated in an oil bath at 110–120° C. for 2.5 hours and then at 130° C. for 2.5 hours. After cooling, the reaction mixture was concentrated and triturated with hexanes. The solid residue was purified by flash chromatography (Biotage 40S; 30:70 ethyl acetate-hexanes) to give the intermediate (±)-1-[1-(2-chloro-pyrimidin-5-yl)-ethyl]-1-(2-fluoro-4-methoxy-phenyl)-3-phenyl-urea. (Yield 0.27 g; 43.2%).

Workup

  1. temperatureheated in an oil bath at 110–120° C. for 2.5 hours
  2. temperatureAfter cooling
  3. concentrationthe reaction mixture was concentrated
  4. customtriturated with hexanes
  5. customThe solid residue was purified by flash chromatography (Biotage 40S; 30:70 ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-dafa2ad316fb4f7eb87aa5c2c775a2e2
Source dataset
uspto-grants-2006_09
Patent number
US07112676B2

Reaction notes

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