Pyrrolopyrimidine five-membered azacyclic derivative and application thereof

1. A pyrrolopyrimidine five-membered azacyclic derivative, a pharmaceutically acceptable salt and hydrate thereof, wherein the structural formula of the derivative is shown in formula (I):

wherein:

X is N or CH;

R 1 is CH 2 CN or COCH 2 CN;

wherein R 3 is SO 2 R 4 or C(O)R 4 , R 4 is a linear or cyclic alkyl group, a linear or branched hydrocarbon chain having at least one double bond, or a linear or cyclic alkyl group substituted with fluorine, NHCH 3 , N(CH 3 ) 2 , phenyl, pyridine or pyrimidine; and

m, and n are each an integer of 0-3, and m+n=3.

2. The pyrrolopyrimidine five-membered azacyclic derivative, the pharmaceutically acceptable salt and hydrate thereof according to claim 1 , wherein, in the pyrrolopyrimidine five-membered azacyclic derivative, pharmaceutically acceptable salt and hydrate thereof, non-exchangeable hydrogen is not substituted, partially or completely substituted by deuterium.

3. The pyrrolopyrimidine five-membered azacyclic derivative, the pharmaceutically acceptable salt and hydrate thereof according to claim 1 , wherein R 4 is a linear or cyclic alkyl group having 1 to 6 carbon atoms or a hydrocarbon group having one double bond and having 2 to 6 carbon atoms.

4. The pyrrolopyrimidine five-membered azacyclic derivative, the pharmaceutically acceptable salt and hydrate thereof according to claim 3 , wherein R 4 is methyl, ethyl, vinyl, or cyclopropyl.

5. The pyrrolopyrimidine five-membered azacyclic derivative, the pharmaceutically acceptable salt and hydrate thereof according to claim 1 , wherein, in the formula (I), R 1 is CH 2 CN and R 3 is SO 2 R 4 .

6. The pyrrolopyrimidine five-membered azacyclic derivative, the pharmaceutically acceptable salt and hydrate thereof according to claim 1 , wherein, in formula (I), R 3 is SO 2 CH 2 CH 3 .

7. The pyrrolopyrimidine five-membered azacyclic derivative, the pharmaceutically acceptable salt and hydrate thereof according to claim 1 , wherein, the pyrrolopyrimidine five-membered azacyclic derivative is one of the compounds represented by the following structural formulas or a mixture of more thereof:

8. A pharmaceutical composition, comprising the pyrrolopyrimidine five-membered azacyclic derivative or the pharmaceutically acceptable salt thereof according to claim 1 , and a pharmaceutically acceptable carrier.

9. A method for preventing and/or treating indications related to JAK kinase function in a mammal, comprising administering an effective amount of the pyrrolopyrimidine five-membered azacyclic derivative, the pharmaceutically acceptable salt and hydrate thereof according to claim 1 , said indications related to JAK kinase function comprise rheumatoid arthritis, polycythemia vera, psoriasis, primary thrombocytosis and myelofibrosis.

10. A method for preparing the pyrrolopyrimidine five-membered azacyclic derivative according to claim 1 , comprising the following steps:

(a) reacting

with a first amino protective reagent PG 1 to obtain

wherein, Z is Cl, Br, or I,

(b) reacting the product obtained in step (a) with

to obtain

wherein, R 5 is an alkoxy group or a silane group which are as amino protecting groups; when R 5 being an alkoxy group, first of all, placing the product obtained in step (a) and

in a mixed solvent of alcohol and water, carrying out the reaction under a palladium catalyst and a basic condition to make the group

replace Z, and then removing R 5 under an acidic reaction condition;

(c) using

wherein PG 2 is a second amino protecting group, and subjecting the product obtained in step (b) to an addition reaction with

followed by deprotection of the second amino protecting group PG 2 under an acidic condition to obtain

wherein R 6 is CHCN or CH(CO)CN, and m, n and R 1 are defined as before;

(d) carrying out a substitution reaction in a polar solvent between the product obtained in step (c) and R 3 —Cl to obtain

then removing the first amino protecting group PG 1 to obtain

11. The pyrrolopyrimidine five-membered azacyclic derivative, the pharmaceutically acceptable salt and hydrate thereof according to claim 2 , wherein, in the formula (I), R 1 is CH 2 CN and R 3 is SO 2 R 4 .

12. The pyrrolopyrimidine five-membered azacyclic derivative, the pharmaceutically acceptable salt and hydrate thereof according to claim 3 , wherein, in the formula (I), R 1 is CH 2 CN and R 3 is SO 2 R 4 .

13. The pyrrolopyrimidine five-membered azacyclic derivative, the pharmaceutically acceptable salt and hydrate thereof according to claim 4 , wherein, in the formula (I), R 1 is CH 2 CN and R 3 is SO 2 R 4 .