3,5-Dichlorobenzoyl chloride → N-(2-(benzo[d]isothiazol-3-ylamino)ethyl)-1-(3,5-dichlorobenzoyl)piperidine-3-carboxamide

HRID 502546Notes

Reaction equation

HRID 502546 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([NH:10][CH2:11][CH2:12][NH:13][C:14]([CH:16]2[CH2:21][CH2:20][CH2:19][NH:18][CH2:17]2)=[O:15])=[N:2]1.C(N(C(C)C)CC)(C)C.[Cl:31][C:32]1[CH:33]=[C:34]([CH:38]=[C:39]([Cl:41])[CH:40]=1)[C:35](Cl)=[O:36]>ClCCl>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([NH:10][CH2:11][CH2:12][NH:13][C:14]([CH:16]2[CH2:21][CH2:20][CH2:19][N:18]([C:35](=[O:36])[C:34]3[CH:33]=[C:32]([Cl:31])[CH:40]=[C:39]([Cl:41])[CH:38]=3)[CH2:17]2)=[O:15])=[N:2]1

Participants

5

Reactant 3

HCID 761913,5-Dichlorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 11856088N-(2-(benzo[d]isothiazol-3-ylamino)ethyl)piperidine-3-carboxamide

Product 1

HCID 57436314N-(2-(benzo[d]isothiazol-3-ylamino)ethyl)-1-(3,5-dichlorobenzoyl)piperidine-3-carboxamideYield 20.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N-(2-(Benzo[d]isothiazol-3-ylamino)ethyl)piperidine-3-carboxamide (75 mg, 0.24 mmol) was dissolved in anhydrous dichloromethane (5 mL) with diisopropylethylamine (38 μL, 0.27 mmol). The solution was cooled on an ice-water bath and then a solution of 3,5-dichlorobenzoyl chloride (57 mg, 0.27 mmol) in dichloromethane (0.5 mL) was added dropwise. The reaction mixture was allowed to stir overnight while warming to room temperature. The solution was washed with saturated sodium bicarbonate solution and brine, then dried over anhydrous sodium sulfate, filtered and the filtrate concentrated under reduced pressure. Purification by column chromatography, on silica gel, eluting with a mixture of 25% ethyl acetate in hexanes and selected fractions were combined and concentrated under reduced pressure to yield N-(2-(benzo[d]isothiazol-3-ylamino)ethyl)-1-(3,5-dichlorobenzoyl)piperidine-3-carboxamide (23 mg). 1H NMR (300 MHz, CDCl3): 7.8 (m, 1H), 7.5 (m, 1H), 7.3 (m, 2H), 7.1 (m, 1H), 6.3 (m, 1H), 3.7 (m, 4H), 3.3 (m, 2H), 2.5 (m, 1H), 1.8 (m, 1H), 1.6 (m, 3H) 1.1 ppm (m, 1H). MW=477 confirmed by LC-MS, tr=3.93 min (Method Y) MH+=478.

Workup

  1. temperatureThe solution was cooled on an ice-water bath
  2. washThe solution was washed with saturated sodium bicarbonate solution and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated under reduced pressure
  6. customPurification by column chromatography
  7. washon silica gel, eluting with a mixture of 25% ethyl acetate in hexanes
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1d995d527e654189bcc89ccd083edfa5
Source dataset
uspto-grants-2010_08
Patent number
US07776847B2

Reaction notes

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