Triethylamine → 4-butoxy-N-(3-(5-phenylbenzo[d]isothiazol-3-ylamino)propyl) benzamide

HRID 502563Notes

Reaction equation

HRID 502563 reaction equation
[C:1]1([C:7]2[CH:8]=[CH:9][C:10]3[S:14][N:13]=[C:12]([NH:15][CH2:16][CH2:17][CH2:18][NH2:19])[C:11]=3[CH:20]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[CH2:28]([O:32][C:33]1[CH:41]=[CH:40][C:36]([C:37](Cl)=[O:38])=[CH:35][CH:34]=1)[CH2:29][CH2:30][CH3:31]>C(Cl)Cl>[CH2:28]([O:32][C:33]1[CH:34]=[CH:35][C:36]([C:37]([NH:19][CH2:18][CH2:17][CH2:16][NH:15][C:12]2[C:11]3[CH:20]=[C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[CH:8]=[CH:9][C:10]=3[S:14][N:13]=2)=[O:38])=[CH:40][CH:41]=1)[CH2:29][CH2:30][CH3:31]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 1185614-Butoxybenzoyl chlorideHCID 58727100N1-(5-Phenylbenzo[d]isothiazol-3-yl)propane-1,3-diamine

Product 1

HCID 574364674-butoxy-N-(3-(5-phenylbenzo[d]isothiazol-3-ylamino)propyl) benzamideYield 14.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The crude N1-(5-Phenylbenzo[d]isothiazol-3-yl)propane-1,3-diamine mixture (˜100 mg, 0.20 mmol) was dissolved in anhydrous methylene chloride with triethylamine (0.3 mL, 0.24 mmol). The mixture was cooled in an ice-bath under nitrogen, then a solution of 4-butoxybenzoyl chloride (51 mg, 0.24 mmol) was added dropwise. 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 methylene chloride 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 4-butoxy-N-(3-(5-phenylbenzo[d]isothiazol-3-ylamino)propyl) benzamide (13 mg). 1H NMR (300 MHz, DMSO-d6): 8.23 (s, 1H), 8.17 (t, 1H), 7.98 (d, 1H), 7.76-7.82 (m, 4H), 7.50 (t, 3H), 7.37-7.40 (m, 1H), 6.97 (d, 2H), 4.00 (t, 2H), 3.50 (q, 2H), 3.39 (q, 2H), 1.90-2.00 (m, 2H), 1.62-1.78 (m, 2H), 1.40-1.49 (m, 2H), 0.96 ppm (t, 3H).

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 methylene chloride
  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-97c1b835eaab4fc4adfeab85325aba3f
Source dataset
uspto-grants-2010_08
Patent number
US07776847B2

Reaction notes

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