Methylurea → (2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-cyclopentyloxyimino-N-(methylcarbamoyl)acetamide

HRID 600950Notes

Reaction equation

HRID 600950 reaction equation
CO[C:3](=[O:23])/[C:4](/[C:12]1[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[C:14]([Cl:22])[CH:13]=1)=[N:5]/[O:6][CH:7]1[CH2:11][CH2:10][CH2:9][CH2:8]1.[CH3:24][NH:25][C:26]([NH2:28])=[O:27].C[O-].[Mg+2].C[O-]>CO>[Cl:22][C:14]1[CH:13]=[C:12](/[C:4](=[N:5]\[O:6][CH:7]2[CH2:8][CH2:9][CH2:10][CH2:11]2)/[C:3]([NH:28][C:26]([NH:25][CH3:24])=[O:27])=[O:23])[CH:17]=[CH:16][C:15]=1[S:18]([CH3:21])(=[O:19])=[O:20]

Participants

5

Reactant 3

HCID 11719MethylureaHCID 164537Methanol, magnesium salt (2:1)HCID 87416800methyl (2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-cyclopentyloxyiminoacetate

Product 1

HCID 59745097(2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-cyclopentyloxyimino-N-(methylcarbamoyl)acetamideYield 36.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
70 °C

Procedure

(E)-(3-Chloro-4-methanesulfonyl-phenyl)-cyclopentyloxyimino-acetic acid methyl ester (prepared as in Example 1, 98 mg, 0.27 mmol), methylurea (44 mg, 0.60 mmol) and a 6-10 wt. % solution of magnesium methoxide in methanol (1.33 mL, 0.10 mmol) were combined and warmed in a 70° C. oil bath for 16 h. After cooling, the reaction mixture was diluted with methanol (2 mL) and filtered through celite. The celite was washed with ethyl acetate (100 mL) and the combined filtrates were washed with water (40 mL), dried over magnesium sulfate and evaporated in vacuo. The residue was purified by flash column chromatography (Merck silica gel 60, 40-63 μm; 50% ethyl acetate/hexanes) to afford (E)-1-[2-(3-chloro-4-methanesulfonyl-phenyl)-2-cyclopentyloxyimino-acetyl]-3-methyl-urea (40 mg, 36%) as a white solid after lyophilization from aqueous dioxane: LC-MS (ESI) m/e calcd for C16H20ClN3O5S [M+] 401.08, found 402 [M+H+]; H1-NMR (400 MHz, CDCl3) δ ppm 1.65 (m, 4 H, 2×CH2), 1.87 (m, 4 H, 2×CH2), 2.94 (d, J=4.9 Hz, 3 H, NCH3), 3.32 (s, 3 H, SO2CH3), 4.92 (m, 1 H, OCH), 7.50 (brd, Jo=8.2, 1 H, Ar), 7.60 (brs, 1 H, Ar), 8.02 (brm, 1 H, NH), 8.21 (d, Jo=8.2 Hz, 1 H, Ar), 8.82 (s, 1 H, NH).

Workup

  1. temperatureAfter cooling
  2. filtrationfiltered through celite
  3. washThe celite was washed with ethyl acetate (100 mL)
  4. washthe combined filtrates were washed with water (40 mL)
  5. dry with materialdried over magnesium sulfate
  6. customevaporated in vacuo
  7. customThe residue was purified by flash column chromatography (Merck silica gel 60, 40-63 μm; 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-b74be251ce754d39b5d7ee9987e7f2e7
Source dataset
uspto-grants-2011_03
Patent number
US07902248B2

Reaction notes

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