Benzo(d)thiazol-2-amine → (2E)-N-(1,3-benzothiazol-2-yl)-2-(3-chloro-4-methylsulfonylphenyl)-2-cyclohexyloxyiminoacetamide

HRID 600964Notes

Reaction equation

HRID 600964 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].[NH2:24][C:25]1[S:26][C:27]2[CH:33]=[CH:32][CH:31]=[CH:30][C:28]=2[N:29]=1.C(N(CC)C(C)C)(C)C>C(#N)C>[S:26]1[C:27]2[CH:33]=[CH:32][CH:31]=[CH:30][C:28]=2[N:29]=[C:25]1[NH:24][C:13](=[O:14])/[C:12](/[C:4]1[CH:5]=[CH:6][C:7]([S:8]([CH3:11])(=[O:10])=[O:9])=[C:2]([Cl:1])[CH:3]=1)=[N:16]/[O:17][CH:18]1[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]1

Participants

5

Reactant 3

HCID 8706Benzo(d)thiazol-2-amineHCID 81531DiisopropylethylamineHCID 87416752(2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-cyclohexyloxyiminoacetic acid

Product 1

HCID 59745101(2E)-N-(1,3-benzothiazol-2-yl)-2-(3-chloro-4-methylsulfonylphenyl)-2-cyclohexyloxyiminoacetamideYield 56.4%

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), 2-aminobenzothiazole (47 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; 60% ethyl acetate/hexanes) to afford (E)-N-benzothiazol-2-yl-2-(3-chloro-4-methanesulfonyl-phenyl)-2-cyclohexyloxyimino-acetamide (86 mg, 56%) as a white solid after lyophilization from aqueous acetonitrile: LC-MS (ESI) m/e calcd for C22H22ClN3O4S2 [M+] 491.07, found 492 [M+H+]; H1-NMR (400 MHz, CDCl3) δ ppm 1.26-1.64 (m, 6H, 3×CH2), 1.75 (m, 2H, 2×CH of CH2), 2.00 (m, 2H, 2×CH of CH2), 3.32 (s, 3 H, SO2CH3), 4.36 (m, 1 H, OCH), 7.35 (brt, 1 H, Ar), 7.48 (brt, 1 H, Ar), 7.65 (dd, Jo=8.2, Jm=1.5 Hz, 1 H, Ar), 7.76 (d, Jm=1.5 Hz, 1 H, Ar), 7.83 (brt, 2H, Ar), 8.23 (d, Jo=8.2 Hz, 1 H, Ar), 10.24 (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; 60% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-349a5fdd436a4f9d98d093230e8b100d
Source dataset
uspto-grants-2011_03
Patent number
US07902248B2

Reaction notes

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