Diisopropylethylamine → N-(3-(4-methylbenzo[d]isothiazol-3-ylamino)propyl)-3-(trifluoromethyl)benzenesulfonamide

HRID 502605Notes

Reaction equation

HRID 502605 reaction equation
[CH3:1][C:2]1[C:7]2[C:8]([NH:11][CH2:12][CH2:13][CH2:14][NH2:15])=[N:9][S:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[F:25][C:26]([F:38])([F:37])[C:27]1[CH:28]=[C:29]([S:33](Cl)(=[O:35])=[O:34])[CH:30]=[CH:31][CH:32]=1>C(Cl)Cl>[CH3:1][C:2]1[C:7]2[C:8]([NH:11][CH2:12][CH2:13][CH2:14][NH:15][S:33]([C:29]3[CH:30]=[CH:31][CH:32]=[C:27]([C:26]([F:25])([F:37])[F:38])[CH:28]=3)(=[O:35])=[O:34])=[N:9][S:10][C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27332503-(Trifluoromethyl)benzenesulfonyl chlorideHCID 58727287HCID 58727287, compound

Product 1

HCID 57436541N-(3-(4-methylbenzo[d]isothiazol-3-ylamino)propyl)-3-(trifluoromethyl)benzenesulfonamideYield 11.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N1-(4-methylbenzo[d]isothiazol-3-yl)propane-1,3-diamine (100 mg, 0.45 mmol) was dissolved in anhydrous methylene chloride with diisopropylethylamine (0.12 mL, 0.63 mmol). The mixture was cooled in an ice-bath under nitrogen and a solution of 3-trifluoromethylbenzenesulfonyl chloride (0.09 mL, 0.54 mmol) in methylene chloride (5 mL) was added drop-wise. After the addition was completed the ice-bath was removed and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane and then washed successively with saturated sodium bicarbonate solution and brine. The organic solution was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by prep-scale reverse phase high performance liquid chromatography to yield N-(3-(4-methylbenzo[d]isothiazol-3-ylamino)propyl)-3-(trifluoromethyl)benzenesulfonamide (23 mg). 1H NMR (300 MHz, DMSO-d6): 7.75 (d, 1H), 7.30 (m, 2H), 7.25 (m, 2H), 6.92 (t, 1H), 6.28 (t, 1H), 3.22 (t, 2H), 2.98 (t, 2H), 2.81 (s, 3H), 2.15 (t, 2H), 1.80 ppm (m, 2H). MW=429 confirmed by LC-MS, tr=3.92 min (Method E) MH+=430.

Workup

  1. temperatureThe mixture was cooled in an ice-bath under nitrogen
  2. additionAfter the addition
  3. customwas removed
  4. additionThe reaction mixture was diluted with dichloromethane
  5. washwashed successively with saturated sodium bicarbonate solution and brine
  6. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by prep-scale reverse phase high performance liquid chromatography

Sources & evidence

ORD record
ord-1ce1ceb925f841e1870cea33db5b116d
Source dataset
uspto-grants-2010_08
Patent number
US07776847B2

Reaction notes

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