4-Nitrophenyl chloroformate → HCID 58587811, compound

HRID 446344Notes

Reaction equation

HRID 446344 reaction equation
[NH2:1][C:2]1[CH:22]=[CH:21][C:5]([O:6][C:7]2[C:12]([C:13]3[CH:18]=[CH:17][N:16]=[C:15]([NH:19][CH3:20])[N:14]=3)=[CH:11][CH:10]=[CH:9][N:8]=2)=[CH:4][CH:3]=1.Cl[C:24](OC1C=CC([N+]([O-])=O)=CC=1)=[O:25].C(O[CH:39](OCC)[CH2:40][NH:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)C>C1COCC1.C(OCC)(=O)C>[CH3:20][NH:19][C:15]1[N:14]=[C:13]([C:12]2[C:7]([O:6][C:5]3[CH:21]=[CH:22][C:2]([N:1]4[CH:39]=[CH:40][N:41]([C:42]5[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=5)[C:24]4=[O:25])=[CH:3][CH:4]=3)=[N:8][CH:9]=[CH:10][CH:11]=2)[CH:18]=[CH:17][N:16]=1

Participants

6

Reactant 3

HCID 821294-Nitrophenyl chloroformateHCID 519978N-(2,2-Diethoxyethyl)anilineHCID 469295414-(2-(4-aminophenoxy)pyridin-3-yl)-N-methylpyrimidin-2-amine

Product 1

HCID 58587811HCID 58587811, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a slurry of 4-(2-(4-amino-phenoxy)pyridin-3-yl)-N-methylpyrimidin-2-amine (0.200 g, 0.682 mmol) in THF (3 mL) under nitrogen was added 4-nitrophenyl chloroformate (0.138 mg, 0.682 mmol). The dark brown mixture was allowed to stir for 1 h, at which point N-(2,2-diethoxyethyl)benzenamine (0.285 mL, 1.36 mmol) was added. The reaction was heated to 80 deg. C. for 30 min. The reaction was cooled to ambient temperature, diluted with ethyl acetate, and washed with 3× saturated aqueous sodium bicarbonate, 2×1N NaOH, 1× water, and 1× brine. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The resulting solid was suspended in dichloromethane and filtered. The filtrate was concentrated to a brown oil, which was treated with 5 mL 1N HCl and was heated to 80 deg. C. in a sealed tube. After 1 h, the reaction was cooled to ambient temperature, filtered, and the solid was rinsed with small amounts of water and ethanol, and was dried in vacuo to give a tan solid. This material was further purified by reverse-phase HPLC using acetonitrile/water/TFA as eluent to give 1-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-3-phenyl-1H-imidazol-2(3H)-one as an off-white solid. MS m/z=437 [M+1]+. Calc'd for C25H20N6O2: 436.47.

Workup

  1. additionwas added
  2. temperatureThe reaction was heated to 80 deg. C
  3. washwashed with 3× saturated aqueous sodium bicarbonate, 2×1N NaOH, 1× water, and 1× brine
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated to a brown oil, which
  9. additionwas treated with 5 mL 1N HCl
  10. temperaturewas heated to 80 deg. C
  11. waitAfter 1 h
  12. temperaturethe reaction was cooled to ambient temperature
  13. filtrationfiltered
  14. washthe solid was rinsed with small amounts of water and ethanol
  15. customwas dried in vacuo
  16. customto give a tan solid
  17. customThis material was further purified by reverse-phase

Sources & evidence

ORD record
ord-98e3d1063ab84261a2a6475b01234f58
Source dataset
uspto-grants-2013_07
Patent number
US08476434B2

Reaction notes

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