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

HRID 600984Notes

Reaction equation

HRID 600984 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](/[C:12](=[N:16]\[O:17][CH2:18][CH:19]([CH3:21])[CH3:20])/[C:13]([OH:15])=O)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].[NH2:22][C:23]1[S:24][C:25]2[CH:31]=[CH:30][CH:29]=[CH:28][C:26]=2[N:27]=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[S:24]1[C:25]2[CH:31]=[CH:30][CH:29]=[CH:28][C:26]=2[N:27]=[C:23]1[NH:22][C:13](=[O:15])/[C:12](/[C:4]1[CH:5]=[CH:6][C:7]([S:8]([CH3:11])(=[O:9])=[O:10])=[C:2]([Cl:1])[CH:3]=1)=[N:16]/[O:17][CH2:18][CH:19]([CH3:21])[CH3:20]

Participants

5

Reactant 3

HCID 8706Benzo(d)thiazol-2-amineHCID 81531DiisopropylethylamineHCID 87416786(2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-(2-methylpropoxyimino)acetic acid

Product 1

HCID 59745092(2E)-N-(1,3-benzothiazol-2-yl)-2-(3-chloro-4-methylsulfonylphenyl)-2-(2-methylpropoxyimino)acetamideYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(E)-(3-chloro-4-methanesulfonyl-phenyl)-isobutoxyimino-acetic acid (prepared as in Example 24, 104 mg, 0.31 mmol), 2-aminobenzothiazole (47 mg, 0.31 mmol) and N,N-diisopropylethylamine (163 μL, 0.94 mmol) were combined in methylene chloride (1.5 mL) and cooled in an ice bath. O-(7-Azabenzotriazole-1-yl)-N,N,N′N′-tetramethyluronium hexafluoro-phosphate (119 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; 30% ethyl acetate/hexanes) to afford (E)-N-benzothiazol-2-yl-2-(3-chloro-4-methanesulfonyl-phenyl)-2-isobutoxyimino-acetamide (86 mg, 60%) as a white solid after lyophilization from aqueous acetonitrile: LC-MS (ESI) m/e calcd for C20H20ClN3O4S2 [M+] 465.06, found 466 [M+H+]; H1-NMR (400 MHz, CDCl3) δ ppm 0.97 (d, J=6.6 Hz, 6 H, 2×CH3), 2.09 (m, 1 H, CH), 3.32 (s, 3 H, SO2CH3), 4.12 (d, J=6.8 Hz, 2 H, OCH2), 7.35 (brt, J=7.8 Hz, 1H, Ar), 7.48 (brt, J=7.8 Hz, 1H, Ar), 7.63 (dd, Jo=8.2, Jm=1.6 Hz, 1 H, Ar), 7.74 (d, Jm=1.6 Hz, 1 H, Ar), 7.83 (m, 2H, Ar), 8.24 (d, Jo=8.2 Hz, 1 H, Ar), 10.25 (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; 30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-46a8eac5b83a47c4a426426d69972d93
Source dataset
uspto-grants-2011_03
Patent number
US07902248B2

Reaction notes

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