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

HRID 600950노트

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HRID 600950 반응식
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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 887Methanol용매2회

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온도
70 °C

실험 절차

(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).

후처리

  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)

출처 및 근거

ORD 기록
ord-b74be251ce754d39b5d7ee9987e7f2e7
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07902248B2

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