N-((R)-1-(naphthalen-1-yl)ethyl) -3-(3-(trifluoroM

hi yet another variation, the reduction of the double bond and amide carbonyl of (E)-N-((i?)-l-naphthalen-l-yl-ethyl)-3-(3-trifluoromethyl-phenyl)-acrylamide is carried out in a stepwise manner. Either the carbonyl group or the alkene double bond can be reduced first. For example, the reduction of the alkene double bond is achieved by hydrogenation in the presence of a metal catalyst.[0123] A suspension of (E)-N-((i?)-l-naphthalen-l-yl-ethyl)-3-(3-trifluoromethyl-phenyl)- acrylamide (1.0 equiv.; 0.67 mmol; 250 mg) and Pd/C 10 wtpercent (25 mg) was stirred in a mixture of methanol and toluene (7 mL/lmL). The reaction flask was evacuated and back filled using a hydrogen filled balloon (three times). The reaction mixture is stirred at room temperature and the progress of the reaction was monitored using high performance liquid chromatography. After 90 minutes, the reaction mixture was filtered over a bed of celite and the solvent from the filtrate was removed in vacuo. The resulting solid was dried overnight at 45Preparation of N-[I -(R)-(I -naphthyl) ethyl]-3-[3-(trifluoromethyl) phenyl]-l- propanamide(X). Thionyl chloride (6.69 ml, 0.0917 moles) was added dropwise to a solution of 3-[3- (trifluoromethyl) phenyl]-2-propanoic acid (10 gm, 0.045 moles), dimethylformamide (0.5 ml) and dry toluene (100 ml) at 25 - 30 Cinacalcet is obtained by reducing the alkyne-amide precursor. In one embodiment, the alkyne was reduced by metal catalyzed hydrogenation. Specifically, to a methanolic solution (7 mL) of 3-(3-trifluoromethyl-phenyl)-propynoic acid ((R)-I- naphthalen-l-yl-ethyl)-amide (1.0 equiv.; 0.68 mmol; 250mg) in a two necked round bottom 3-(Trifluoromethyl) phenylpropionic acid (6) (327.3 mg, 1.5 mmol) was weighed into a 50 mL reaction flask.Dichloromethane (10 mL) and DMF (3 drops) were added and stirred to dissolve.The temperature of the mixture was lowered to 0 C, oxalyl chloride (0.27 mL, 3.0 mmol) was added, the reaction mixture was warmed to room temperature, and the reaction was stirred for 2 h.The solvent and excess oxalyl chloride were removed under reduced pressure.The crude (R)-N-(1-naphthylethyl)-3-(3-trifluoromethylphenyl)propanoyl chloride was obtained. The crude (R)-N-(1-naphthylethyl)-3-(3-trifluoromethylphenyl)propanoyl chloride was dissolved in dichloromethane (10 mL).The temperature of the solution was then lowered to 0 C, and pyridine (120 muL) and (R)-1-naphthylethylamine (5) (342.0 mg, 2.0 mmol) were slowly added.Stirring was continued for 2 h at 0 C.After completion of the reaction, the reaction mixture was extracted with dichloromethane (3×20 mL).The organic phase was washed with saturated aqueous sodium hydrogen sulfate (30 mL).(dichloromethane: ethyl acetate/2:1) purified, Obtained a white solid (R)-N-(1-naphthylethyl)-3-(3-trifluoromethylphenyl)propaneAmide (7) (690.0 mg, 93% yield, 87% ee).Amide 7 was recrystallized from n-hexane:ethyl acetate/10:1.Its optical purity is increased to >99% and the recovery is 53%.

Molecular Weight:371.4
XLogP3:5.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:5
Exact Mass:371.14969875
Monoisotopic Mass:371.14969875
Topological Polar Surface Area:29.1
Heavy Atom Count:27
Complexity:492
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes