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

HRID 600966Notes

Reaction equation

HRID 600966 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](/[C:12](=[N:22]\[O:23][CH:24]2[CH2:28][CH2:27][CH2:26][CH2:25]2)/[C:13]([NH:15][C:16]2C=CN(C)[N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].[CH3:29][C:30]1N=C(N)[S:32][N:31]=1.C(N(CC)C(C)C)(C)C>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4](/[C:12](=[N:22]\[O:23][CH:24]2[CH2:25][CH2:26][CH2:27][CH2:28]2)/[C:13]([NH:15][C:16]2[S:32][N:31]=[C:30]([CH3:29])[N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 3506395-Amino-3-methyl-1,2,4-thiadiazoleHCID 59745110(2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-cyclopentyloxyimino-N-(1-methylpyrazol-3-yl)acetamide

Product 1

HCID 87416799(2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-cyclopentyloxyimino-N-(3-methyl-1,2,4-thiadiazol-5-yl)acetamideYield 50%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

(E)-(3-Chloro-4-methanesulfonyl-phenyl)-cyclopentyloxyimino-acetic (prepared as in Example 1, 96 mg, 0.28 mmol), 3-methyl-[1,2,4]thiadiazol-5-ylamine (32 mg, 0.28 mmol) and N,N-diisopropylethylamine (145 μL, 0.83 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 (106 mg, 0.28 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-cyclopentyloxyimino-N-(3-methyl-[1,2,4]thiadiazol-5-yl)-acetamide (62 mg, 50%) as a white solid after lyophilization from aqueous acetonitrile: LC-MS (ESI) m/e calcd for C17H19ClN4O4S2 [M+] 442.05, found 443 [M+H+]; H1-NMR (400 MHz, CDCl3) δ ppm 1.67 (m, 4 H, 2×CH2), 1.90 (m, 4 H, 2×CH2), 2.60 (s, 3 H, ArCH3), 3.32 (s, 3 H, SO2CH3), 4.95 (m, 1 H, OCH), 7.60 (dd, Jo=8.3, Jm=1.6 Hz, 1 H, Ar), 7.70 (d, Jm=1.6 Hz, 1 H, Ar), 8.22 (d, Jo=8.3 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-bffe805ea1fb4838bf6154dc42ffefb9
Source dataset
uspto-grants-2011_03
Patent number
US07902248B2

Reaction notes

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