N-(2,2-Diphenylethyl)-2-(6-methoxynaphthalen-2-yl)propanamide

N-(2,2-Diphenylethyl)-2-(6-methoxynaphthalen-2-yl)propanamide was prepared by a reaction between 2,2-diphenylethan-1-amine and naproxen in high yield. The newly obtained naproxen derivative was fully analyzed and characterized via 1H, 13C, UV, IR, and mass spectral data.


Introduction
Naproxen 1 (Figure 1) is part of the aryl propionic family of non-steroidal antiinflammatory drugs (NSAIDs). NSAIDs are commonly used worldwide. They can be either selective or non-selective cyclooxygenase (COX) inhibitors. Profens are considered one of the most important groups of non-selective COX inhibitors used in the treatment of inflammation associated with tissue injury [1].
An easy and handy synthetic procedure for amide synthesis is the N,N′-dicyclohexylcarbodiimide (DCC)-mediated coupling between carboxylic acids and amines. DCC is used for the preparation of esters, amides, or anhydrides. DCC reacts with the carboxyl group of naproxen to produce an activated acylating agent that reacts with the amino group of the other molecule to form an amide bond.
The resultant compound is characterized by its melting point, 1 H and 13 C-NMR, UV, IR, and HRMS spectra.

Materials and Methods
All reagents and chemicals were purchased from commercial sources (Sigma-Aldrich S.A. and Riedel-de Haën, Sofia, Bulgaria) and used as received. Melting points were determined on a Boetius hot stage apparatus and are uncorrected. The NMR spectral data were recorded on a Bruker Avance II +600 spectrometer (BAS-IOCCP-Sofia, Bruker, Billerica, MA, USA). 1 H-NMR and 13 C-NMR spectra for compound 3 were taken in DMSO-d6 at 600 MHz and at 150.9 MHz, respectively. Chemical shifts are given in relative ppm and were referenced to tetramethylsilane (TMS) (δ = 0.00 ppm) as an internal standard; the coupling constants are indicated in Hz. The NMR spectra were recorded at room temperature (ac. 295 K). Mass analyses were carried out on a Q Exactive Plus mass spectrometer (Thermo Fisher Scientific, Waltham, MA, USA). TLC was carried out on precoated 0.2 mm Fluka silica gel 60 plates (Merck KGaA, Darmstadt, Germany).
An easy and handy synthetic procedure for amide synthesis is the N,N′-dicyclohexylcarbodiimide (DCC)-mediated coupling between carboxylic acids and amines. DCC is used for the preparation of esters, amides, or anhydrides. DCC reacts with the carboxyl group of naproxen to produce an activated acylating agent that reacts with the amino group of the other molecule to form an amide bond.
The resultant compound is characterized by its melting point, 1 H and 13 C-NMR, UV, IR, and HRMS spectra.

Materials and Methods
All reagents and chemicals were purchased from commercial sources (Sigma-Aldrich S.A. and Riedel-de Haën, Sofia, Bulgaria) and used as received. Melting points were determined on a Boetius hot stage apparatus and are uncorrected. The NMR spectral data were recorded on a Bruker Avance II +600 spectrometer (BAS-IOCCP-Sofia, Bruker, Billerica, MA, USA). 1 H-NMR and 13 C-NMR spectra for compound 3 were taken in DMSO-d6 at 600 MHz and at 150.9 MHz, respectively. Chemical shifts are given in relative ppm and were referenced to tetramethylsilane (TMS) (δ = 0.00 ppm) as an internal standard; the coupling constants are indicated in Hz. The NMR spectra were recorded at room temperature (ac. 295 K). Mass analyses were carried out on a Q Exactive Plus mass spectrometer (Thermo Fisher Scientific, Waltham, MA, USA). TLC was carried out on precoated 0.2 mm Fluka silica gel 60 plates (Merck KGaA, Darmstadt, Germany). An easy and handy synthetic procedure for amide synthesis is the N,N -dicyclohexylcarbodiimide (DCC)-mediated coupling between carboxylic acids and amines. DCC is used for the preparation of esters, amides, or anhydrides. DCC reacts with the carboxyl group of naproxen to produce an activated acylating agent that reacts with the amino group of the other molecule to form an amide bond.
The resultant compound is characterized by its melting point, 1 H and 13 C-NMR, UV, IR, and HRMS spectra.

Materials and Methods
All reagents and chemicals were purchased from commercial sources (Sigma-Aldrich S.A. and Riedel-de Haën, Sofia, Bulgaria) and used as received. Melting points were determined on a Boetius hot stage apparatus and are uncorrected. The NMR spectral data were recorded on a Bruker Avance II +600 spectrometer (BAS-IOCCP-Sofia, Bruker, Billerica, MA, USA). 1 H-NMR and 13 C-NMR spectra for compound 3 were taken in DMSOd 6 at 600 MHz and at 150.9 MHz, respectively. Chemical shifts are given in relative ppm and were referenced to tetramethylsilane (TMS) (δ = 0.00 ppm) as an internal standard; the coupling constants are indicated in Hz. The NMR spectra were recorded at room temperature (ac. 295 K). Mass analyses were carried out on a Q Exactive Plus mass spectrometer (Thermo Fisher Scientific, Waltham, MA, USA). TLC was carried out on precoated 0.2 mm Fluka silica gel 60 plates (Merck KGaA, Darmstadt, Germany).
Synthesis of N-(2,2-Diphenylethyl)-2-(6-methoxynaphthalen-2-yl)propanamide 3 N,N'-Dicyclohexylcarbodiimide (1 mmol, 0.206 g) was added to a solution of naproxen (1 mmol, 0.230 g) in CH 2 Cl 2 . The reaction mixture was stirred at room temperature for 10 min. After the addition of 2,2-diphenylethylamine (1 mmol, 0.197 g), the reaction mixture was stirred for 50 min and the formation of white crystalline dicyclohexylurea was observed and then separated by filtration over a sintered glass filter. The filtrate was washed with a diluted hydrochloric acid, a saturated solution of Na 2 CO 3 , and brine. The combined organic layers were dried over anhydrous Na 2 SO 4 , and the solvent was removed under reduced pressure.  Figure S1: 1 H-NMR spectrum of compound 3, Figure S2: 13 C-NMR spectrum of compound 3, Figure S3: UV spectrum of compound 3, Figure S4: ESI-HRMS of compound 3, Figure S5: IR spectrum of compound 3.