New methotrexate crystal form and preparation method thereof

Abstract

The invention provides a novel methotrexate crystal form and a preparation method thereof, and the method comprises the following steps: S1) adding water to dissolve methotrexate sodium salt with a structure as shown in a formula I to obtain a clear solution; s2) adjusting the pH value of the clarified solution to 1-2 by using an acid solution, and stirring and crystallizing for 1-2 hours; s3) adding the solid obtained in the step S2) into a mixed solvent, adjusting the pH value to 4-5 by adopting triethylamine, stirring for 1-2 hours, and carrying out suction filtration; and S4) adding the solid obtained in the step S3) into a mixed solvent, stirring for 2-3 hours, carrying out suction filtration to separate the solid, and drying to obtain the novel methotrexate crystal form. According to the method, the methotrexate raw material is purified while the new crystal form is prepared, and the purity of methotrexate reaches 99% or above, so that the methotrexate purification operation is simpler, the yield is higher, the production cost is reduced, and the method is more suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a new crystal form of methotrexate and a preparation method thereof. Background technique [0002] The chemical name of methotrexate is N-[4-[[(2,4-diamino-6-pteridine)methyl]methylamino]benzoyl]-L-glutamic acid, according to literature reports, synthetic formazan There are many routes of aminopterin. [0003] Method 1: post-synthesis pteridine ring method (A'+(B+C)) [0004] [0005] Method 2: One Pot Method [0006] [0007] This route is a one-pot synthesis of methotrexate. It is equivalent to generating Fragment A in situ and then condensing with Fragment B+C. [0008] Method 3: followed by glutamic acid method [0009] [0010] Method 4: Condensation method (A+(B+C)) [0011] [0012] The reaction conditions of this route are mild, and both intermediates are commercially available. [0013] From the above, it can be known that there are many s...

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Problems solved by technology

[0013] As can be seen from the above, there are many synthetic methods, and there is no report on the crystal form of methotrexate

At the same time, in view of the fact that in the preparation, the crystal form of the raw material directly or indirectly affects the preparation process of the corresponding preparation, the dissolution and absorption of the corresponding preparation in vivo and in vitro, and then affects the safety, effectiveness and quality controllability of the drug.

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