PYRAZOLE COMPOUNDS AND METHODS FOR MAKING AND USING THE COMPOUNDS

1 . A compound having a formula

or salt thereof, wherein:

R is aliphatic, heteroaliphatic, heteroaryl, aryl, halo, amide or CN;

R 1 is H, aliphatic or heteroaliphatic;

or R and R 1 , together with the atoms to which they are attached, form a heterocyclyl ring;

R 2 is H, aliphatic, heteroaliphatic, heterocycloaliphatic, aryl, amide, heterocyclyl or araliphatic;

each R 3 independently is H, aliphatic, halogen, heteroaliphatic, —O-aliphatic, heterocyclyl, aryl, araliphatic, —O-heterocyclyl, hydroxyl, nitro, cyano, carboxyl, carboxyl ester, acyl, amide, amino, sulfonyl, sulfonamide, sulfanyl, sulfinyl, haloalkyl, alkylphosphate, or alkylphosphonate;

y is from 1 to 6; and

Het-1 is heteroaryl.

2 . A method, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 .

3 . The method of claim 2 , wherein the compound has a structure

4 . The method of claim 3 , wherein the method is a method for treating a disease or condition for which an IRAK inhibitor is indicated, comprising administering to the subject an amount of the compound effective to treat the disease or condition.

5 . The method of claim 4 , wherein the disease or condition comprises an auto-immune disease, inflammatory disorder, cardiovascular disease, neurodegenerative disorder, allergic disorder, multi-organ failure, kidney disease, platelet aggregation, cancer, transplantation, sperm motility, erythrocyte deficiency, graft rejection, lung injury, respiratory disease, ischemic condition, bacterial infection, viral infection, immune regulatory disorder or a combination thereof.

6 . The method of claim 5 , wherein the disease or condition comprises an auto-immune disease, inflammatory disorder, cardiovascular disease, cancer, ischemic condition, immune regulatory disorder or a combination thereof.

7 . The method of claim 5 , wherein the disease or condition comprises an autoimmune disease, an inflammatory disorder, or both.

8 . The method of claim 5 , wherein the cancer is breast cancer, lung cancer, melanoma, leukemia, large B-cell lymphoma, Waldenström's macroglobulinemia, myelodysplastic syndromes, Kaposi's sarcoma, or a combination thereof.

9 . The method of claim 4 , wherein the disease or condition comprises a myelodysplastic syndrome.

10 . The method of claim 3 , wherein the compound is in the form of a pharmaceutically acceptable salt.

11 . A method, comprising:

a) treating a compound having a formula

with an acid compound having a formula

to form a compound having a formula

and

b) treating the compound having a formula

with a pyrazolyl boronic acid or boronic ester compound to form compound having a formula

wherein

R is aliphatic, heteroaliphatic, heteroaryl, aryl, halo, amide or CN;

R 3 is H, aliphatic, halogen, heteroaliphatic, —O-aliphatic, heterocyclyl, aryl, araliphatic, —O-heterocyclyl, hydroxyl, nitro, cyano, carboxyl, carboxyl ester, acyl, amide, amino, sulfonyl, sulfonamide, sulfanyl, sulfinyl, haloalkyl, alkylphosphate, or alkylphosphonate;

R x is alkyl;

LG is a leaving group;

Het-1 is heteroaryl; and

Het-2 is pyrazolyl.

12 . The method of claim 11 , further comprising:

i) treating a compound having a formula

with a compound having a formula

to form a compound having a formula

ii) treating the compound having a formula

with a first reducing agent to form an alcohol compound;

iii) treating the alcohol compound with an alkyl halide to form a compound having a formula

and

iv) treating the compound having a formula

with a second reducing agent to form the compound having a formula

wherein the first reducing agent is selected from a borohydride reagent or an aluminum hydride reagent; and

the second reducing agent is selected from hydrogen gas in the presence of a catalyst, a borohydride reagent, zinc metal in acetic acid, or iron powder.