1,3,4-Thiadiazole, 2-amino-5-methyl- → HCID 59745095, compound

HRID 600985Notes

Reaction equation

HRID 600985 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](/[C:12](=[N:16]\[O:17][CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)/[C:13]([OH:15])=O)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].[CH3:23][C:24]1[S:28][C:27]([NH2:29])=[N:26][N:25]=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4](/[C:12](=[N:16]\[O:17][CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)/[C:13]([NH:29][C:27]2[S:28][C:24]([CH3:23])=[N:25][N:26]=2)=[O:15])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Participants

5

Reactant 3

HCID 669491,3,4-Thiadiazole, 2-amino-5-methyl-HCID 81531DiisopropylethylamineHCID 87416741HCID 87416741, compound

Product 1

HCID 59745095HCID 59745095, compoundYield 45.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(E)-(3-Chloro-4-methanesulfonyl-phenyl)-cyclopentyloxyimino-acetic acid (prepared as in Example 1, 100 mg, 0.29 mmol), 5-methyl-[1,3,4]thiadiazol-2-ylamine (37 mg, 0.32 mmol) and N,N-diisopropylethylamine (166 μL, 0.95 mmol) were combined in methylene chloride (2 mL) and cooled in an ice bath. O-(7-Azabenzotriazole-1-yl)-N,N,N′N′-tetramethyluronium hexafluorophosphate (121 mg, 0.32 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; 60% ethyl acetate/hexanes) to afford (E)-2-(3-chloro-4-methanesulfonyl-phenyl)-2-cyclopentyloxyimino-N-(5-methyl-[1,3,4]thiadiazol-2-yl)-acetamide (58 mg, 45%) as a white solid after lyophilization from aqueous acetonitrile: LC-MS (ESI) m/e calcd for C17H19ClN4O4S [M+] 442.05, found 443 [M+H+]; H1-NMR (400 MHz, CDCl3) δ ppm 1.67 (m, 4 H, 2×CH2), 1.89 (m, 4 H, 2×CH2), 2.75 (s, 3 H, ArCH3), 3.32 (s, 3 H, SO2CH3), 4.97 (m, 1 H, OCH), 7.58 (dd, Jo=8.2, Jm=1.5 Hz, 1 H, Ar), 7.68 (d, Jm=1.5 Hz, 1 H, Ar), 8.22 (d, Jo=8.2 Hz, 1 H, Ar), 10.33 (brs, 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; 60% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-0a36385ff50a479daeb9ecfb0837cb87
Source dataset
uspto-grants-2011_03
Patent number
US07902248B2

Reaction notes

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