HCID 10114706, compound → HCID 10181381, compound

HRID 1935189Notes

Reaction equation

HRID 1935189 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([NH:11][C:12](=[O:32])[CH:13]([C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[CH:22][CH:21]=2)[CH2:14][CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[S:9][CH:10]=1)=[O:5])C>CO.S(=O)(=O)(O)O>[CH3:1][O:3][C:4]([C:6]1[N:7]=[C:8]([NH:11][C:12](=[O:32])[CH:13]([C:20]2[CH:21]=[CH:22][C:23]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)=[CH:24][CH:25]=2)[CH2:14][CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[S:9][CH:10]=1)=[O:5]

Participants

4

Reactant 1

HCID 10114706HCID 10114706, compound

Product 1

HCID 10181381HCID 10181381, compoundYield 41%

Reagents, catalysts & solvents 2

HCID 1118Sulfuric AcidCatalystHCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 2-(2-biphenyl-4-yl-3-cyclopentyl-propionylamino)-thiazole-4-carboxylic acid ethyl ester (prepared in Example 1B-d, 200 mg, 0.45 mmol) in methanol (4 mL) was treated with concentrated sulfuric acid (2 drops). The reaction mixture was heated under reflux for 15 h. The reaction mixture was allowed to cool to 25° C. and then concentrated in vacuo to remove methanol. The resulting residue was partitioned between water and ethyl acetate. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 2/1 hexanes/ethyl acetate) afforded 2-(2-biphenyl-4-yl-3-cyclopentyl-propionylamino)-thiazole-4-carboxylic acid methyl ester (80 mg, 41%) as a white solid: mp 98-101° C.; FAB-HRMS m/e calcd for C25H26N2O3S (M+H)+ 435.1743, found 435.1752.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureunder reflux for 15 h
  3. concentrationconcentrated in vacuo
  4. customto remove methanol
  5. customThe resulting residue was partitioned between water and ethyl acetate
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c34f4ea1f3554260b231af13224d6a71
Source dataset
uspto-grants-2002_05
Patent number
US06384220B2

Reaction notes

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