Diethyl Ether → 3-[6-(2-Fluoro-4-{3-[2-(4-fluorophenyl)acetyl]ureido}phenoxy)pyrimidin-4-yl]-1,1-dimethylurea

HRID 492810Notes

Reaction equation

HRID 492810 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH2:11])=[O:10])=[CH:4][CH:3]=1.C(Cl)(=O)[C:13](Cl)=[O:14].[NH2:18][C:19]1[CH:37]=[CH:36][C:22]([O:23][C:24]2[N:29]=[CH:28][N:27]=[C:26]([NH:30][C:31](=[O:35])[N:32]([CH3:34])[CH3:33])[CH:25]=2)=[C:21]([F:38])[CH:20]=1.C(OCC)C>ClCCCl.CN(C)C=O.CCCCCC>[F:38][C:21]1[CH:20]=[C:19]([NH:18][C:13]([NH:11][C:9](=[O:10])[CH2:8][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)=[O:14])[CH:37]=[CH:36][C:22]=1[O:23][C:24]1[N:29]=[CH:28][N:27]=[C:26]([NH:30][C:31](=[O:35])[N:32]([CH3:34])[CH3:33])[CH:25]=1

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 65578Oxalyl chlorideHCID 5731202-(4-Fluorophenyl)acetamideHCID 231531933-[6-(4-Amino-2-fluorophenoxy)pyrimidin-4-yl]-1,1-dimethylurea

Product 1

HCID 231535473-[6-(2-Fluoro-4-{3-[2-(4-fluorophenyl)acetyl]ureido}phenoxy)pyrimidin-4-yl]-1,1-dimethylureaYield 49.8%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
110 °C

Procedure

2-(4-Fluorophenyl)acetamide (125 mg) was dissolved in 1,2-dichloroethane (9 ml) under a nitrogen atmosphere, and then oxalyl chloride (0.10 ml) was added thereto, followed by stirring at 110° C. overnight. The reaction mixture was concentrated under a reduced pressure to give a residue, which was then dissolved in N,N-dimethylformamide (1 ml) under a nitrogen atmosphere. A solution of 3-[6-(4-amino-2-fluorophenoxy)pyrimidin-4-yl]-1,1-dimethylurea (90 mg) in N,N-dimethylformamide (2 ml) was then added thereto, followed by stirring for 30 min. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate, water and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:3). Fractions containing the target compound were concentrated to give a residue, to which diethyl ether (2 ml)-hexane (1 ml) was added to suspend. The solid was filtered off and dried under aeration to provide the titled compound (72.4 mg, 49.8%) as a pale yellow solid.

Workup

  1. concentrationThe reaction mixture was concentrated under a reduced pressure
  2. customto give a residue, which
  3. stirringby stirring for 30 min
  4. customThe reaction mixture was partitioned between ethyl acetate and water
  5. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate, water and brine in this order
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated
  8. customto give a residue, which
  9. customwas then purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:3)
  10. additionFractions containing the target compound
  11. concentrationwere concentrated
  12. customto give a residue
  13. filtrationThe solid was filtered off
  14. customdried under aeration

Sources & evidence

ORD record
ord-ce116fe2bfc64035905ddae6f2c6b772
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

Loading…