N-((R)-1-(naphthalen-1-yl)ethyl)-3-(3-(trifluoroMethyl)phenyl)propanaMide Chemical Properties

Melting point:

90-92℃ (cyclohexane )

Boiling point:

530.5±50.0 °C(Predicted)

Density 

1.210±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

solubility 

Chloroform (Slightly), Methanol (Slightly)

form 

Solid

pka

15.18±0.46(Predicted)

color 

Off-White to Light Brown

Stability:

Hygroscopic

InChI

InChI=1S/C22H20F3NO/c1-15(19-11-5-8-17-7-2-3-10-20(17)19)26-21(27)13-12-16-6-4-9-18(14-16)22(23,24)25/h2-11,14-15H,12-13H2,1H3,(H,26,27)/t15-/m1/s1

InChIKey

GDEHAOJGPHEOSO-OAHLLOKOSA-N

SMILES

C1(CCC(N[C@@H](C2=C3C(C=CC=C3)=CC=C2)C)=O)=CC=CC(C(F)(F)F)=C1

N-((R)-1-(naphthalen-1-yl)ethyl)-3-(3-(trifluoroMethyl)phenyl)propanaMide Usage And Synthesis

Uses

N-((R)-1-(naphthalen-1-yl)ethyl)-3-(3-(trifluoroMethyl)phenyl)propanaMide is a pharmaceutical intermediate ingredient used in the preparation of cinacalcet and its salts. Cinacalcet is used for the management and treatment of secondary hyperparathyroidism (in the dialysis population), primary hyperparathyroidism (where the patient may not be a candidate for surgical treatment), and for the treatment of end-stage renal disease or the prevention of calcification in dialysis patients.

Synthesis

In another synthetic scheme, the reduction of the double bond and amide carbonyl group of (E)-N-((R)-1-naphthalen-1-yl-ethyl)-3-(3-trifluoromethylphenyl)acrylamide is carried out in a stepwise manner. Optionally, either the carbonyl or the olefinic double bond is reduced first. In the case of the reduction of the olefinic double bond, the reaction is realized by hydrogenation in the presence of a metal catalyst. This was done as follows: (E)-N-((R)-1-naphthalen-1-yl-ethyl)-3-(3-trifluoromethylphenyl)acrylamide (1.0 equiv; 0.67 mmol; 250 mg) was suspended with 10 wt% Pd/C (25 mg) in a solvent mixture of methanol and toluene (7 mL/1 mL). The reaction flask was evacuated and backfilled with a hydrogen balloon (repeated three times). The reaction mixture was stirred at room temperature and the progress of the reaction was monitored by high performance liquid chromatography (HPLC).After 90 min, the reaction mixture was filtered through a bed of diatomaceous earth and the solvent in the filtrate was removed under vacuum. The resulting solid was dried in a vacuum oven at 45 °C overnight. The isolated yield was 91.2% (229 mg). The structure of the product was confirmed by 1H NMR and mass spectrometry.1H NMR (400 MHz, CDCl3) δ ppm: 1.6 (d, 3H), 2.39-2.53 (m, 2H), 2.96-3.13 (m, 2H), 5.55 (br.s, 1H), 5.87-5.96 (m, 1H), 7.29-7.38 (m, 2H), 7.39-7.46 (m, 2H), 7.29-7.38 (m, 2H), 7.39-7.38 (m, 2H). 7.39-7.46 (m, 4H), 7.46-7.55 (m, 2H), 7.76-7.82 (m, 1H), 7.83-7.89 (m, 1H), 8.00-8.07 (m, 1H). High Resolution Mass Spectrometry (HRMS) (M+1): 372.1.

References

[1] Patent: WO2009/2427, 2008, A2. Location in patent: Page/Page column 39
[2] Patent: WO2008/58235, 2008, A2. Location in patent: Page/Page column 34
[3] Patent: EP1990333, 2008, A1. Location in patent: Page/Page column 12

N-((R)-1-(naphthalen-1-yl)ethyl)-3-(3-(trifluoroMethyl)phenyl)propanaMide(1005450-55-4)Related Product Information

• (αR)-α-Methyl-N-[3-[3-(trifluoroMethyl)phenyl)propyl]-1-napthaleneMethanaMine-N-oxide
• (R)-1-(5,6-dihydronaphthalen-1-yl)ethan-1-amine
• 3-(3-Trifluoromethylphenyl)propionic acid
• Cinacalcet hydrochloride
• 1'-Acetonaphthone
• Methanesulfonic acid 3-(3-trifluoroMethylphenyl)propyl ester
• 3-(3-METHYLPHENYL)PROPIONIC ACID
• N-(1-(5,6,7,8-tetrahydronaphthalen-1-yl)ethyl)-3-(3-(trifluoromethyl)phenyl)propanamide
• 3-[o-(alpha,alpha,alpha-trifluorotolyl)]propionic acid
• 1-NaphthaleneMethanaMine, 5,6,7,8-tetrahydro-α-Methyl-, (αR)-
• 1-NaphthaleneMethanaMine, α-Methyl-N-[[3-(trifluoroMethyl)phenyl]Methyl]-, (αR)-
• (R)-1-(Naphthalen-2-yl)ethanamine hydrochloride
• (R)-N-(1-(naphthalen-1-yl)ethyl)-3-(M-tolyl)propan-1-aMine
• Cinacalcet 7,8-Dihydro Racemate HCl
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• 4-(TRIFLUOROMETHYL)HYDROCINNAMIC ACID
• Cinacalcet Impurity D
• 3-(3'-TRIFLUOROMETHYL PHENYL) PROPANOL