Methanol → 1-[3-Cyclopentyl-2-(4-pyridin-3-yl-phenyl)-propionyl]-3-methyl-urea

HRID 1935278Notes

Reaction equation

HRID 1935278 reaction equation
CO[C:3](=[O:23])[CH:4]([C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=2)=[CH:13][CH:12]=1)[CH2:5][CH:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1.[CH3:24][NH:25][C:26]([NH2:28])=[O:27].C[O-].[Mg+2].C[O-].CO>>[CH:6]1([CH2:5][CH:4]([C:11]2[CH:12]=[CH:13][C:14]([C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)=[CH:15][CH:16]=2)[C:3]([NH:28][C:26]([NH:25][CH3:24])=[O:27])=[O:23])[CH2:10][CH2:9][CH2:8][CH2:7]1

Participants

5

Reactant 4

HCID 887MethanolHCID 11719MethylureaHCID 164537Methanol, magnesium salt (2:1)HCID 674834933-Cyclopentyl-2-(4-pyridin-3-yl-phenyl)-propionic acid methyl ester

Product 1

HCID 99464671-[3-Cyclopentyl-2-(4-pyridin-3-yl-phenyl)-propionyl]-3-methyl-ureaYield 6%

Conditions

Temperature
25 °C

Procedure

A mixture of 3-cyclopentyl-2-(4-pyridin-3-yl-phenyl)-propionic acid methyl ester (275 mg, 0.89 mmol) and methyl urea (165 mg, 2.22 mmol) was treated with a solution of magnesium methoxide in methanol (7.4 wt. %, 5.5 mL, 2.67 mmol). The reaction mixture was then concentrated in vacuo to approximately one-half the volume of methanol. The resulting reaction mixture was then heated under reflux for 3 d. The reaction mixture was allowed to cool to 25° C. and then partitioned between water and ethyl acetate. The layers were separated, and the aqueous layer was further extracted with ethyl acetate (2×40 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 1/3 hexanes/ethyl acetate) afforded 1-[3-cyclopentyl-2-(4-pyridin-3-yl-phenyl)-propionyl]-3-methyl-urea (17 mg, 6%) as a white solid: mp 158-160° C.; FAB-HRMS m/e calcd for C21H25N3O2 (M+H)+ 352.2025, found 352.2028.

Workup

  1. concentrationThe reaction mixture was then concentrated in vacuo to approximately one-half the volume of methanol
  2. customThe resulting reaction mixture
  3. temperaturewas then heated
  4. temperatureunder reflux for 3 d
  5. custompartitioned between water and ethyl acetate
  6. customThe layers were separated
  7. extractionthe aqueous layer was further extracted with ethyl acetate (2×40 mL)
  8. dry with materialThe combined organic extracts were dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9b0430cb40dc42dd929ddaa01ec914e6
Source dataset
uspto-grants-2002_05
Patent number
US06384220B2

Reaction notes

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