Urea → HCID 22013857, compound

HRID 1532728Notes

Reaction equation

HRID 1532728 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[C:10]1[O:11][C:12]([CH3:29])=[C:13]([CH2:15][CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][C:26]([OH:28])=O)=[CH:20][CH:19]=2)[N:14]=1.S(Cl)(Cl)=O.[NH2:34][C:35]([NH2:37])=[O:36]>>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[C:10]1[O:11][C:12]([CH3:29])=[C:13]([CH2:15][CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][C:26]([NH:34][C:35]([NH2:37])=[O:36])=[O:28])=[CH:20][CH:19]=2)[N:14]=1

Participants

4

Reactant 3

HCID 1176Urea2×HCID 24386Thionyl ChlorideHCID 22013885HCID 22013885, compound

Product 1

HCID 22013857HCID 22013857, compoundYield 21%

Conditions

Temperature
60 °C

Procedure

To 3-[4-[2-(2-(benzothiophen-2-yl)-5-methyl-4-oxazolyl)ethoxy]phenyl]propionic acid (850 mg, 2.09 mmol) obtained in Example 14 was added thionyl chloride (2 ml, 27.4 mmol) and the mixture was stirred under heating for 40 min at 60° C. The reaction mixture was concentrated and N,N-dimethylaniline (10 ml) was added to the residue. Urea (250 mg, 4.17 mmol) was added and the mixture was stirred under heating for 5 hr at 150° C. Urea (250 mg, 4.17 mmol) was again added and the mixture was heated for 10 hr at 150° C. The reaction mixture was cooled to room temperature and the precipitated solid (468 mg) was collected by filtration. A part (260 mg) thereof was washed successively with water, ethyl acetate/tetrahydrofuran (9:1), 10% aqueous sodium hydroxide solution, 1N hydrochloric acid, water and tetrahydrofuran, and dried to give the title compound (110 mg, yield 21%) as a gray-white solid.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionN,N-dimethylaniline (10 ml) was added to the residue
  3. stirringthe mixture was stirred
  4. temperatureunder heating for 5 hr at 150° C
  5. temperaturethe mixture was heated for 10 hr at 150° C
  6. temperatureThe reaction mixture was cooled to room temperature
  7. filtrationthe precipitated solid (468 mg) was collected by filtration
  8. washA part (260 mg) thereof was washed successively with water, ethyl acetate/tetrahydrofuran (9:1), 10% aqueous sodium hydroxide solution, 1N hydrochloric acid, water and tetrahydrofuran
  9. customdried

Sources & evidence

ORD record
ord-a6203b54bb7b43dbb4066c86a2f3d929
Source dataset
uspto-grants-2001_03
Patent number
US06204277B1

Reaction notes

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