POSACONAZOLE PHOSPHATE MONOCHOLINATE, PREPARATION METHOD AND USE THEREOF

1 . A compound (posaconazole phosphate monocholinate) of formula (I):

wherein n is an integer of 0˜12, preferably an integer of 0˜8, more preferably an integer of 0˜6.

2 . A method for preparing the compound of formula (I) according to claim 1 , comprising steps of:

(a) reacting a compound of formula A with a compound of formula B in the absence of a solvent or in an organic solvent A in the present of an inert gas so as to form a compound of formula C;

(b) hydrolyzing the compound of formula C formed in the step (a) by using a solvent B so as to form a compound of formula D:

(c) reacting the compound of formula D obtained in the step (b) with choline hydroxide in a solvent C so as to prepare the compound of formula (I).

3 . The method according to claim 2 , wherein in the step (a), the inert gas is selected from one or more of nitrogen, helium or argon, preferably nitrogen or argon;

preferably, in the step (a), the organic solvent A is selected from one or more of an aromatic hydrocarbon solvent, a halohydrocarbon solvent, a nitrile solvent, a ketone solvent, an ether solvent, triethylamine, diethylamine, pyridine, 1-methylimidazole, N,N-diisopropyl ethylamine and an ester solvent, preferably ethyl acetate, acetonitrile, tetrahydrofuran, dichloromethane, toluene, acetone, triethylamine, 1-methylimidazole, pyridine or chloroform;

preferably, in the step (b), the solvent B is selected from one or more of water, an alkaline aqueous solution and an aqueous organic solvent solution; the alkaline aqueous solution is preferably an aqueous solution of sodium hydroxide, ammonium hydroxide, an aqueous solution of potassium hydroxide or an aqueous solution of sodium carbonate;

and the aqueous organic solvent solution is preferably an aqueous solution of methanol, an aqueous solution of ethanol, an aqueous solution of isopropanol or an aqueous solution of acetone;

preferably, in the step (c), the solvent C is selected from one or more of water, aromatic hydrocarbons, halohydrocarbons, nitriles, ketones, ethers, alcohols and esters; preferably selected from one or more of water, acetonitrile, methanol, ethanol, acetone, isopropanol, tetrahydrofuran, ethyl acetate, dichloromethane, toluene and butanone.

4 . The method according to claim 2 , wherein in the step (a),

reaction temperature is −10° C.˜50° C., preferably 0° C.˜35° C.;

preferably, in the step (b), hydrolysis temperature is −20° C.˜30° C., preferably −5° C.˜10° C.;

preferably, in the step (c), reaction temperature is −10° C.˜80° C., preferably 10° C.˜40° C.

5 . The method according to claim 2 , wherein in the step (a), molar ratio of the compound of formula A to the compound of formula B is 1:

(1.0˜20.0), preferably 1:(2.25˜10.0);

preferably, in the step (c), molar ratio of the compound of formula D to the choline hydroxide is 1:(0.5˜2), preferably 1:1.05.

6 . Use of the compound according to claim 1 in preparation of a drug resisting fungal infection; preferably, the fungal infection is an infection caused by Candida or Cryptococcus.

7 . A pharmaceutical composition, comprising the compound of formula (I) according to claim 1 and a pharmaceutically acceptable excipient;

preferably, the pharmaceutical composition is a tablet, a suppository agent, a dispersible tablet, an enteric-coated tablet, a chewable tablet, an orally disintegrating tablet, a capsule, a sugar-coated tablet, a granule, dry powder, oral solution, a small volume injection, lyophilized powder for injection or a large volume parenteral solution;

preferably, the pharmaceutically acceptable excipient is selected from one or more of the following excipients: a pH regulator, a diluent, a disintegrating agent, a suspending agent, a lubricating agent, a binder, a filler, a flavoring agent, a sweetening agent, an antioxidant, a preservative, a coating agent and coloring agent.