4-Methoxybenzylamine → 3-chloro-N-(4-methoxybenzyl)benzo[d]isothiazole-5-sulfonamide

HRID 502575Notes

Reaction equation

HRID 502575 reaction equation
[Cl:1][C:2]1[C:6]2[CH:7]=[C:8]([S:11](Cl)(=[O:13])=[O:12])[CH:9]=[CH:10][C:5]=2[S:4][N:3]=1.C(N(C(C)C)CC)(C)C.[CH3:24][O:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30][NH2:31])=[CH:28][CH:27]=1>C(Cl)Cl>[Cl:1][C:2]1[C:6]2[CH:7]=[C:8]([S:11]([NH:31][CH2:30][C:29]3[CH:32]=[CH:33][C:26]([O:25][CH3:24])=[CH:27][CH:28]=3)(=[O:13])=[O:12])[CH:9]=[CH:10][C:5]=2[S:4][N:3]=1

Participants

5

Reactant 3

HCID 754524-MethoxybenzylamineHCID 81531DiisopropylethylamineHCID 574365563-Chlorobenzo[d]isothiazole-5-sulfonyl chloride

Product 1

HCID 587270493-chloro-N-(4-methoxybenzyl)benzo[d]isothiazole-5-sulfonamideYield 45.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-chlorobenzo[d]isothiazole-5-sulfonyl chloride (90 mg, 0.33 mmol) in methylene chloride (2 mL), diisopropylethylamine (142 μL, 0.82 mmol) and 4-methoxybenzylamine (85 μL, 0.65 mmol) were added at room temperature. After stirring for 6 h, the reaction mixture was diluted with methylene chloride (20 mL) and washed with 10% HCl aqueous solution and brine. The organic layer was then dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give a brown residue. Purification by column chromatography, on silica gel, eluting with 2:8 ethyl acetate:hexanes provided 3-chloro-N-(4-methoxybenzyl)benzo-[d]isothiazole-5-sulfonamide (55 mg). 1H NMR (300 MHz, CDCl3): 8.22 (dd, 1H), 7.82 (dd, 1H), 7.75 (dd, 1H), 7.10 (d, 2H), 6.73 (d, 2H), 5.06 (t, 1H), 4.18 (d, 2H), 3.73 ppm (s, 3H). MW=368 confirmed by LC-MS, tr=13.39 min (Method Y) MH+=369.

Workup

  1. washwashed with 10% HCl aqueous solution and brine
  2. dry with materialThe organic layer was then dried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customto give a brown residue
  6. customPurification by column chromatography
  7. washon silica gel, eluting with 2:8 ethyl acetate

Sources & evidence

ORD record
ord-4bb4cc9cb3574a1da1b93c956d5b9e32
Source dataset
uspto-grants-2010_08
Patent number
US07776847B2

Reaction notes

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