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

HRID 1935288Notes

Reaction equation

HRID 1935288 reaction equation
CO[C:3](=[O:23])[CH:4]([C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]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:16]=[CH:15][C:14]([N:17]3[CH2:18][CH2:19][O:20][CH2:21][CH2:22]3)=[CH:13][CH:12]=2)[C:3]([NH:28][C:26]([NH:25][CH3:24])=[O:27])=[O:23])[CH2:7][CH2:8][CH2:9][CH2:10]1

Participants

5

Reactant 4

HCID 887MethanolHCID 11719MethylureaHCID 164537Methanol, magnesium salt (2:1)HCID 67483527HCID 67483527, compound

Product 1

HCID 101091211-[3-Cyclopentyl-2-(4-morpholin-4-yl-phenyl)-propionyl]-3-methyl-ureaYield 11%

Conditions

Temperature
25 °C

Procedure

A mixture of 3-cyclopentyl-2-(4-morpholin-4-yl-phenyl)-propionic acid methyl ester (364.0 mg, 1.15 mmol) and methyl urea (254.8 mg, 3.44 mmol) was treated with a solution of magnesium methoxide in methanol (7.4 wt. %, 6.6 mL, 4.59 mmol). The resulting reaction mixture was heated under reflux for 3 d. The reaction mixture was allowed to cool to 25° C. and then filtered through a pad of celite. The pad of celite was washed well with ethyl acetate until the washings showed the absence of product by thin layer chromatography. The filtrate was then concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 3/1 hexanes/ethyl acetate then 1/1 hexanes/ethyl acetate) afforded 1-[3-cyclopentyl-2-(4-morpholin-4-yl-phenyl)-propionyl]-3-methyl-urea (43.5 mg, 11%) as a white solid: mp 206-207° C.; FAB-HRMS m/e calcd for C20H29N3O3 (M+) 359.2209, found 359.2206.

Workup

  1. customThe resulting reaction mixture
  2. temperaturewas heated
  3. temperatureunder reflux for 3 d
  4. filtrationfiltered through a pad of celite
  5. washThe pad of celite was washed well with ethyl acetate until the washings
  6. concentrationThe filtrate was then concentrated in vacuo

Sources & evidence

ORD record
ord-0bcaf5cb62f0470ab3121910fb80cecc
Source dataset
uspto-grants-2002_05
Patent number
US06384220B2

Reaction notes

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