合成路线1

2) The reaction of N-(2,3-epoxypropyl)phthalimide (I) with dibenzylamine (II) at 80 C gives 1-(dibenzylamino)-3-(phthalimido)-2-propanol (III), which is hydrolyzed with refluxing concentrated HCl to afford 1-amino-3-(dibenzylamino)-2-propanol (IV). The acylation of (IV) with chloroacetyl chloride (V) in CHCl3 yields the corresponding chloroacetamide (VI), which is cyclized by means of potassium tert-butoxide in refluxing ethanol to give 6-(dibenzylaminomethyl)morpholin-3-one (VII). The debenzylation of (VII) with H2 over Pd(OH)2/C in ethanol yields 6-(aminomethyl)morpholin-3-one (VIII), which is condensed with 4-(acetamido)-5-chloro-2-ethoxybenzoyl chloride (IX) by means of triethylamine in CHCl3 to afford the monoacetylated derivative of metabolite M-2 (X). Finally, this compound is hydrolyzed with HCl in refluxing ethanol/water to give metabolite M-2. The two final steps of this sequence can also be performed in a single step by condensation of morpholinone (VIII) with 4-amino-5-chloro-2-ethoxybenzoic acid (XI) by means of carbonyldiimidazole (CDI) in THF to afford directly the metabolite M-2 after neutralization with aqueous NH4OH.