Sodium Carbonate → 1-[6-(4-Fluoro-Phenylamino)-pyrimidin-4-yl]-3-(4-methoxy-phenyl)-1-methyl-urea

HRID 1038690Notes

Reaction equation

HRID 1038690 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][CH3:16])[N:12]=[CH:11][N:10]=2)=[CH:4][CH:3]=1.[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]=[C:26]=[O:27])=[CH:21][CH:20]=1.C([O-])(=O)C.C([O-])(=O)C.C([Sn+2]CCCC)CCC.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]2[N:10]=[CH:11][N:12]=[C:13]([N:15]([CH3:16])[C:26]([NH:25][C:22]3[CH:21]=[CH:20][C:19]([O:18][CH3:17])=[CH:24][CH:23]=3)=[O:27])[CH:14]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 794431-Isocyanato-4-methoxybenzene2×HCID 9798523Di-n-butyl diacetoxy tinHCID 66669841N4-(4-fluorophenyl)-N6-methylpyrimidine-4,6-diamine

Product 1

HCID 577104091-[6-(4-Fluoro-Phenylamino)-pyrimidin-4-yl]-3-(4-methoxy-phenyl)-1-methyl-urea

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of N-(4-fluoro-phenyl)-N′-methyl-pyrimidine-4,6-diamine (2.18 g, 10 mmol), 4-methoxyphenyl isocyanate (1.29 mL, 10 mmol) and dibutyltin diacetate (0.54 mL, 2 mmol) in dry dioxane (20 mL) is shaken for 6 h at 100° C. After addition of a second portion of 4-methoxyphenyl isocyanate (0.9 mL, 7 mmol) stirring is continued at 100° C. for 9 h. The reaction mixture is treated with ethyl acetate and half-saturated Na2CO3 solution. The organic layer is filtered, dried over Na2SO4, evaporated, and the residue purified by flash chromatography (hexane/ethyl acetate). The combined pure fractions are evaporated, the residue is suspended in hot CH3OH and the hot mixture filtered. This procedure is repeated several times. The solid thus obtained is dried in vacuo to afford the title compound.

Workup

  1. stirringstirring
  2. waitis continued at 100° C. for 9 h
  3. filtrationThe organic layer is filtered
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customthe residue purified by flash chromatography (hexane/ethyl acetate)
  7. customThe combined pure fractions are evaporated
  8. filtrationthe hot mixture filtered
  9. customThe solid thus obtained
  10. customis dried in vacuo

Sources & evidence

ORD record
ord-5e48edc5e0c342388cf2e5c6cd372d8d
Source dataset
uspto-grants-2013_10
Patent number
US08552002B2

Reaction notes

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