Diisopropylethylamine → (2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-cyclohexyloxyimino-N-(3-methyl-1,2,4-thiadiazol-5-yl)acetamide

HRID 600963Notes

Reaction equation

HRID 600963 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](/[C:12](=[N:16]\[O:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)/[C:13](O)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].[CH3:24][C:25]1[N:29]=[C:28]([NH2:30])[S:27][N:26]=1.C(N(CC)C(C)C)(C)C>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4](/[C:12](=[N:16]\[O:17][CH:18]2[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]2)/[C:13]([NH:30][C:28]2[S:27][N:26]=[C:25]([CH3:24])[N:29]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 3506395-Amino-3-methyl-1,2,4-thiadiazoleHCID 87416752(2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-cyclohexyloxyiminoacetic acid

Product 1

HCID 59745096(2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-cyclohexyloxyimino-N-(3-methyl-1,2,4-thiadiazol-5-yl)acetamideYield 40.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

(E)-(3-Chloro-4-methanesulfonyl-phenyl)-cyclohexyloxyimino-acetic acid (prepared as in Example 9, 112 mg, 0.31 mmol), 3-methyl-[1,2,4]thiadiazol-5-ylamine (36 mg, 0.31 mmol) and N,N-diisopropylethylamine (163 μL, 0.93 mmol) were combined in acetonitrile (1.25 mL) and cooled in an ice bath. O-(7-Azabenzotriazole-1-yl)-N,N,N′N′-tetramethyluronium hexafluorophosphate (118 mg, 0.31 mmol) was added and the ice bath was removed. After stirring 2 h, the reaction mixture was evaporated in vacuo. The residue was treated with saturated aqueous sodium bicarbonate solution (1 mL) and extracted with chloroform (2×3 mL). The combined organic phases were dried over sodium sulfate and evaporated in vacuo. The residue was purified by flash column chromatography (Merck silica gel 60, 40-63 μm; 40% ethyl acetate/hexanes) to afford (E)-2-(3-chloro-4-methanesulfonyl-phenyl)-2-cyclohexyloxyimino-N-(3-methyl-[1,2,4]thiadiazol-5-yl)-acetamide (57 mg, 40%) as a white solid after lyophilization from aqueous acetonitrile: LC-MS (ESI) m/e calcd for C18H21ClN4O4S2 [M+] 456.07, found 457 [M+H+]; H1-NMR (400 MHz, CDCl3) δ ppm 1.25-1.64 (m, 6H, 3×CH2), 1.73 (m, 2H, 2×CH of CH2), 2.00 (m, 2H, 2×CH of CH2), 2.60 (s, 3 H, ArCH3), 3.31 (s, 3 H, SO2CH3), 4.37 (m, 1 H, OCH), 7.64 (dd, Jo=8.2, Jm=1.5 Hz, 1 H, Ar), 7.74 (d, Jm=1.5 Hz, 1 H, Ar), 8.23 (d, Jo=8.2 Hz, 1 H, Ar), 10.35 (s, 1 H, NH).

Workup

  1. temperaturecooled in an ice bath
  2. customthe ice bath was removed
  3. customthe reaction mixture was evaporated in vacuo
  4. additionThe residue was treated with saturated aqueous sodium bicarbonate solution (1 mL)
  5. extractionextracted with chloroform (2×3 mL)
  6. dry with materialThe combined organic phases were dried over sodium sulfate
  7. customevaporated in vacuo
  8. customThe residue was purified by flash column chromatography (Merck silica gel 60, 40-63 μm; 40% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-619570e987b041eb88e28bc8fc5514d3
Source dataset
uspto-grants-2011_03
Patent number
US07902248B2

Reaction notes

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