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

HRID 600955Notes

Reaction equation

HRID 600955 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](/[C:12](=[N:16]\[O:17][CH:18]([CH3:20])[CH3:19])/[C:13]([OH:15])=O)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].[NH2:21][C:22]1[S:23][C:24]2[CH:30]=[CH:29][CH:28]=[CH:27][C:25]=2[N:26]=1.C(N(CC)C(C)C)(C)C>C(#N)C>[S:23]1[C:24]2[CH:30]=[CH:29][CH:28]=[CH:27][C:25]=2[N:26]=[C:22]1[NH:21][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][CH:18]([CH3:20])[CH3:19]

Participants

5

Reactant 3

HCID 8706Benzo(d)thiazol-2-amineHCID 81531DiisopropylethylamineHCID 87416770(2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-propan-2-yloxyiminoacetic acid

Product 1

HCID 24990018(2E)-N-(1,3-benzothiazol-2-yl)-2-(3-chloro-4-methylsulfonylphenyl)-2-propan-2-yloxyiminoacetamideYield 54.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

This estimated 80% pure (E)-(3-chloro-4-methanesulfonyl-phenyl)-isopropoxyimino-acetic acid (prepared as in Example 6, 99 mg, 0.31 mmol), 2-aminobenzothiazole (512 mg, 0.34 mmol) and N,N-diisopropylethylamine (162 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; 50% ethyl acetate/hexanes) to afford (E)-N-benzothiazol-2-yl-2-(3-chloro-4-methanesulfonyl-phenyl)-2-isopropoxyimino-acetamide (76 mg, 54%) as a white solid after lyophilization from aqueous acetonitrile: LC-MS (ESI) m/e calcd for C19H18ClN3O4S2 [M+] 451.04, found 452 [M+H+]; H1-NMR (400 MHz, CDCl3) δ ppm 1.39 (d, J=6.3 Hz, 6 H, 2×CH3), 3.32 (s, 3 H, SO2CH3), 4.65 (m, J=6.3 Hz, 1 H, OCH), 7.36 (brt, J=7.8 Hz, 1H, Ar), 7.49 (brt, J=7.8 Hz, 1H, Ar), 7.64 (dd, Jo=8.2, Jm=1.6 Hz, 1 H, Ar), 7.74 (d, Jm=1.6 Hz, 1 H, Ar), 7.84 (m, 2H, Ar), 8.24 (d, Jo=8.2 Hz, 1 H, Ar), 10.20 (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; 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-503b4dd317184ca9971233def1023c19
Source dataset
uspto-grants-2011_03
Patent number
US07902248B2

Reaction notes

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