Condensed-ring pyrimidylamino derivative, preparation method therefor, and intermediate, pharmaceutical composition and applications thereof

1. A condensed-ring pyrimidylamino derivative having a structure of formula II-1, a tautomer, a mesomer, a racemate, a stereoisomer, a pharmaceutically acceptable salt or a prodrug thereof:

wherein,

X is S;

Y is CR 4 ;

W is C;

ring A is an aromatic ring or a heteroaromatic ring;

R 1 is selected from hydrogen atom, hydroxyl, a halogen, an alkyl, a sulfonyl, an alkoxy, formyl, amino, an amide or a heteroaryl, or the two adjacent R 1 (s) and the two atoms on the ring A connected to them form a 5- to 7-membered heterocyclic ring together; in the heterocyclic ring, the heteroatom(s) is(are) oxygen and/or nitrogen, the number of the heteroatom(s) is 1 to 4, and the number of carbon atom(s) is 1 to 6;

where, in R 1 , the alkyl, the alkoxy, the formyl, the amino, the sulfonyl or the heteroaryl are optionally independently substituted by a substituent selected from the group consisting of a halogen, a C 1-10 alkyl, hydroxy, amino, a C 1-10 alkoxy, a C 1-4 sulfonyl and a heterocycloalkyl having 3 to 8 carbon atoms in which the heteroatom is oxygen and/or nitrogen and the number of the heteroatom(s) is 1 to 4; the heterocycloalkyl ring is optionally substituted by a substituent selected from the group consisting of a C 1-4 alkyl;

R 2 is selected from an amide or a heterocycloalkyl which is piperidinyl;

where, in R 2 , the heterocycloalkyl which is piperidinyl is optionally substituted by a substituent selected from the group consisting of: hydroxy, a C 1-4 alkyl and a C 1-4 acyl;

or R 2 is

ring B is an aromatic ring or a heteroaromatic ring,

m is 1 or 2,

R 3 is selected from hydrogen atom, hydroxyl, a halogen, an alkyl, an alkoxy, or the two adjacent R 3 (s) together with the carbon atoms on the ring B to which they are attached to form a 5- to 7-membered heterocyclyl together; the heterocyclyl is a heterocyclyl wherein the heteroatom is selected from the group consisting of oxygen, nitrogen and sulfur, the number of the heteroatom(s) is 1 to 4, and the number of carbon atoms is 2 to 6;

where, in R 3 , the alkyl or the alkoxy is optionally independently substituted by a substituent selected from the group consisting of a halogen, a C 1-4 alkyl, hydroxy, amino, a C 1-4 alkoxy, a C 1-4 sulfonyl and an amide; and the heterocyclyl is optionally substituted by a substituent selected from the group consisting of a C 1-4 alkyl;

R 4 is selected from hydrogen atom, a halogen or an alkyl;

n is 1 or 2; and

the amide is

2. The condensed-ring pyrimidylamino derivative, the tautomer, the mesomer, the racemate, the stereoisomer, the pharmaceutically acceptable salt or the prodrug thereof according to claim 1 , wherein, the condensed-ring pyrimidylamino derivative having the structure of formula II-1 is represented by formula III-1-1 or III-1-2,

3. The condensed-ring pyrimidylamino derivative, the tautomer, the mesomer, the racemate, the stereoisomer, the pharmaceutically acceptable salt or the prodrug thereof according to claim 1 , wherein:

in the ring A, the aromatic ring is a C 6-10 aromatic ring, and in the ring A, the heteroaromatic ring is a heteroaromatic ring having 2 to 5 carbon atoms in which the heteroatom is nitrogen atom and the number of the heteroatom(s) is 1 to 3;

in the ring B, the aromatic ring is a C 6-10 aromatic ring, and in the ring B, the heteroaromatic ring is a heteroaromatic ring having 2 to 5 carbon atoms in which the heteroatom is a nitrogen atom and the number of the heteroatom(s) is 1 to 3;

in the R 1 , the halogen is fluorine or chlorine; the alkyl is a C 1-4 alkyl; the sulfonyl is a C 1-4 sulfonyl; the alkoxy is a C 1-4 alkoxy; the heteroaryl is a heteroaryl having 2 to 5 carbon atoms in which the heteroatom is nitrogen atom and the number of the heteroatom(s) is 1 to 3; the carbon heterocyclic ring is one having 2 to 5 carbon atoms in which the heteroatom is oxygen, the number of the heteroatom(s) is 1 or 2; and

in the R 3 , the alkyl is a C 1-4 alkyl; the alkoxy is a C 1-4 alkoxy; the heterocyclyl is a heterocyclyl having 2 to 4 carbon atoms in which the heteroatom is oxygen and the number of the heteroatom(s) is 1 to 2.

4. The condensed-ring pyrimidylamino derivative, the tautomer, the mesomer, the racemate, the stereoisomer, the pharmaceutically acceptable salt or the prodrug thereof according to claim 3 , wherein:

in the ring A, the C 6-10 aromatic ring is benzene ring, the heteroaromatic ring is a heteroaromatic ring having 2 to 3 carbon atoms in which the heteroatom is nitrogen atom and the number of the heteroatom(s) is 1 or 2;

in the ring B, the C 6-10 aromatic ring is benzene ring, in the ring B, the heteroaromatic ring is a heteroaromatic ring having 2 to 3 carbon atoms in which the heteroatom is nitrogen atom and the number of the heteroatom(s) is 1 or 2; and

in the R 1 , the C 1-4 sulfonyl is methanesulfonyl, the heteroaryl is pyrazolyl, the carbon heterocyclic ring is one having 3 to 5 carbon atoms in which the heteroatom is oxygen, the number of the heteroatom(s) is 1 or 2.

5. The condensed-ring pyrimidylamino derivative, the tautomer, the mesomer, the racemate, the stereoisomer, the pharmaceutically acceptable salt or the prodrug thereof according to claim 4 , wherein:

in the ring A, the heteroaromatic ring is a pyrazole ring or triazole ring; and

in the ring B, the heteroaromatic ring is pyrazole ring.

6. The condensed-ring pyrimidylamino derivative, the tautomer, the mesomer, the racemate, the stereoisomer, the pharmaceutically acceptable salt or the prodrug thereof according to claim 1 , wherein:

in the substituent(s) of R 1 , the halogen is fluorine; the C 1-10 alkyl is a C 1-4 alkyl; the C 1-10 alkoxy is a C 1-4 alkoxy; the C 1-4 sulfonyl is methanesulfonyl, the heterocycloalkyl is a heterocycloalkyl having 4 to 6 carbon atoms in which the heteroatom is oxygen and/or nitrogen, the number of the heteroatom(s) is 1 to 4; and

in the substituent(s) of R 3 , the halogen is fluorine, and the C 1-4 sulfonyl is methanesulfonyl.

7. The condensed-ring pyrimidylamino derivative, the tautomer, the mesomer, the racemate, the stereoisomer, the pharmaceutically acceptable salt or the prodrug thereof according to claim 6 , wherein, in the substituent(s) of R 1 , the heterocycloalkyl is morpholinyl.

8. The condensed-ring pyrimidylamino derivative, the tautomer, the mesomer, the racemate, the stereoisomer, the pharmaceutically acceptable salt or the prodrug thereof according to claim 1 , wherein,

the R 1 is

methyl,

methoxy, ethoxy, trifluoromethyl, fluorine,

the R 2 is

the R 3 is methoxy, isopropoxy, methyl,

isopropyl,

and

the R 4 is methyl or fluorine.

9. The condensed-ring pyrimidylamino derivative, the tautomer, the mesomer, the racemate, the stereoisomer, the pharmaceutically acceptable salt or the prodrug thereof according to claim 1 , wherein,

the

is

and

the

is

10. Any one of the compounds selected from the group consisting of the following compounds:

11. A pharmaceutical composition, which comprises a therapeutically effective amount of a compound selected from the group consisting of the condensed-ring pyrimidylamino derivative, the tautomer, the mesomer, the racemate, the stereoisomer thereof, the pharmaceutically acceptable salt and the prodrug thereof according to claim 1 , and a pharmaceutically acceptable carrier and/or a diluter.

12. A method for inhibiting anaplastic lymphoma kinase activity in a subject in need thereof, comprising administering to the subject a medicament comprising an effective amount of the condensed-ring pyrimidylamino derivative, the tautomer, the mesomer, the racemate, the stereoisomer, thereof, the pharmaceutically acceptable salt or the prodrug thereof according to claim 1 .

13. A method for inhibiting anaplastic lymphoma kinase activity in a subject in need thereof, comprising administering to the subject a medicament comprising an effective amount of the pharmaceutical composition according to claim 11 .

14. A process for preparing the condensed-ring pyrimidylamino derivative, the tautomer, the mesomer, the racemate, the stereoisomer, the pharmaceutically acceptable salt or the prodrug thereof according to claim 1 , comprising: in a solvent, in the presence of a palladium-containing catalyst, allowing a compound represented by formula I-a and a compound represented by formula I-b′ to have a coupling reaction, and then preparing a compound represented by formula I by means of a deprotection reaction

in formula I-a, formula I-b′ and formula I, both U and V are a chemical bond, other substituents are as defined in claim 1 , R 7 is R 2 that is protected by Boc;

or, optionally, a base is also included in the coupling reaction, where the base is sodium carbonate, potassium carbonate or cesium carbonate, and the molar ratio of the base to the compound I-a is from 1:1 to 5:1.

15. The process according to claim 14 , further comprising: in a solvent, in the presence of a palladium-containing catalyst, reacting a compound having a structure of I-c and a compound having a structure of I-d by a coupling reaction to deliver the compound of formula I-a,

wherein, R 5 is a halogen, R 6 is a boric acid or a borate.

16. The process according to claim 14 , wherein the solvent is an organic solvent and/or water, where the organic solvent is selected from the group consisting of 1,4-dioxane, toluene, ethylene glycol dimethyl ether and N,N-dimethylformamide, the volume-to-mass ratio of the organic solvent to the compound having the structure of formula I-a is from 10 mL/g to 110 mL/g, and, when the solvent is organic solvent and water, the amount of the water is 1 to 100% of the volume of the organic solvent.

17. The process according to claim 14 , wherein the palladium-containing catalyst is selected from the group consisting of:

tris(dibenzylideneacetone)dipalladium, palladium acetate, tetrakis(triphenylphosphine)palladium and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II);

where the molar ratio of the palladium-containing catalyst to the compound having the structure of formula I-a is from 0.005:1 to 0.5:1.

18. The process according to claim 14 , wherein the molar ratio of the compound having the structure of formula I-a to the compound having the structure of formula I-b′ is from 0.5:1 to 2:1.

19. The process according to claim 14 , wherein the temperature of the coupling reaction is from 50° C. to 150° C.