Method for preparing sphingosine-1-phosphate receptor agonist

1 . A method for preparing a compound of Formula 7 below or a salt thereof, comprising:

1) a step for preparing a compound of Formula 4 by coupling a compound of Formula 2 with a compound of Formula 3 in the presence of a dimethylacetamide (DMA) solvent;

2) a step for reacting the compound of Formula 4 and a compound of Formula 5 under a reducing condition to prepare a compound of Formula 6 or a salt thereof; and

3) a step for converting an ester group of the compound of Formula 6 or the salt thereof to a carboxylic acid group to prepare a compound of Formula 7 or a salt thereof:

wherein

R1 is hydrogen or a substituted or unsubstituted alkyl,

R2 is hydrogen, a substituted or unsubstituted alkyl, a halogen, CN, CF 3 , or COCF 3 ,

R3 and R4 are each hydrogen, a substituted or unsubstituted alkyl, or a halogen,

R5 is hydrogen, a substituted or unsubstituted alkyl, or a halogen,

R6 is a substituted or unsubstituted alkyl,

X is C or N,

Y is N, O, or S,

L is a leaving group, and

m and n are each 0, 1, 2, or 3, and m+n>0.

2 . The preparation method of claim 1 , wherein R1 is a C 1 -C 4 substituted or unsubstituted alkyl,

R2 is a halogen,

R3 and R4 are each hydrogen or a C 1 -C 4 substituted or unsubstituted alkyl,

R5 is a halogen,

R6 is a C 1 -C 4 substituted or unsubstituted alkyl,

X is N,

Y is N, and

L is a leaving group selected from chlorine (Cl), bromine (Br), iodine (I), methanesulfonate (Oms), p-toluenesulfonate (OTs), and trifluoromethanesulfonate (OTf).

3 . The preparation method of claim 1 , further comprising 4) a step for recrystallizing the compound of Formula 7 or the salt thereof under an acidic condition.

4 . The preparation method of claim 3 , wherein the content of a dichloromethane (DCM) solvent in a fraction containing the recrystallized compound of Formula 7 or the salt thereof is 600 ppm or less.

5 . The preparation method of claim 3 , wherein a solvent for recrystallization includes water, an ester solvent, an alcohol solvent, or a mixed solvent thereof.

6 . The preparation method of claim 5 , wherein the solvent for recrystallization includes water, isopropyl acetate, and ethanol.

7 . The preparation method of claim 3 , wherein the recrystallization step comprises adding an acid compound at a temperature of 0-25° C.

8 . The preparation method of claim 3 , wherein the recrystallization step comprises stirring at a speed of 100 to 500 rpm.

9 . The preparation method of claim 7 , wherein the acid compound is added dropwise for 100 minutes.