Phenyl chloroformate → HCID 59509129, compound

HRID 1020080Notes

Reaction equation

HRID 1020080 reaction equation
Cl[C:2](OC1C=CC=CC=1)=[O:3].[CH3:11][O:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[C:19]1[N:24]=[CH:23][N:22]=[C:21]([NH2:25])[CH:20]=1.CCN(C(C)C)C(C)C.Cl.[CH2:36]([O:38][C:39](=[O:42])[CH2:40][NH2:41])[CH3:37]>ClCCl.O1CCOCC1>[CH2:36]([O:38][C:39](=[O:42])[CH2:40][NH:41][C:2]([NH:25][C:21]1[CH:20]=[C:19]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[O:12][CH3:11])[N:24]=[CH:23][N:22]=1)=[O:3])[CH3:37]

Participants

7

Reactant 4

HCID 15891Phenyl chloroformateHCID 81531Diisopropylethylamine2×HCID 2723640Glycine ethyl ester, hydrochlorideHCID 497584396-(2-Methoxyphenyl)pyrimidin-4-amine

Product 1

HCID 59509129HCID 59509129, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

Phenyl chloroformate (0.370 g, 1.98 mmol) was added dropwise to a solution of 6-(2-methoxy-phenyl)-pyrimidin-4-ylamine (XXIV) (0.25 g, 1.2 mmol) and DIPEA (0.31 g, 2.4 mmol) in dichloromethane (10 ml) at −78° C. and the mixture was allowed to stir overnight at room temperature. Then dichloromethane was evaporated, dry 1,4-dioxane and glycine ethyl ester hydrochloride (0.17 g, 1.2 mmol) and DIPEA (0.31 g, 2.4 mmol) were added and the mixture was heated overnight at 70° C. The solvent was evaporated and the crude product was extracted with ethyl acetate (2×100 ml). The ethyl acetate phase was washed with water (2×50 ml) and brine, dried over anhydrous sodium sulfate and concentrated in a vacuum rotavapor. The residue was purified by silica gel column chromatography (eluent: 70% ethyl acetate/hexane) giving {3-[6-(2-methoxy-phenyl)-pyrimidin-4-yl]-ureido}-acetic acid ethyl ester. Yield: 190 mg, 47.8%.

Workup

  1. customThen dichloromethane was evaporated
  2. temperaturethe mixture was heated overnight at 70° C
  3. customThe solvent was evaporated
  4. extractionthe crude product was extracted with ethyl acetate (2×100 ml)
  5. washThe ethyl acetate phase was washed with water (2×50 ml) and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in a vacuum rotavapor
  8. customThe residue was purified by silica gel column chromatography (eluent: 70% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-d00bdf061cee411984b8842ff9d18f7a
Source dataset
uspto-grants-2014_05
Patent number
US08716296B2

Reaction notes

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