Modulators of toll-like receptors
Provided are modulators of TLRs of Formula II: pharmaceutically acceptable salts thereof, compositions containing such compounds, and therapeutic methods that include the administration of such compounds.
1. A method of preparing a compound, comprising:
(a) forming a reaction mixture comprising 1-butanol, an acid, and a compound having the structure:
under conditions suitable to prepare a compound having the structure:
(b) forming a reaction mixture comprising the compound produced in step (a), a reducing agent and hydrogen, under conditions suitable to prepare the compound having the structure:
2. The method of claim 1 , wherein the acid comprises trifluoroacetic acid.
3. The method of claim 1 , wherein the reducing agent comprises Raney Ni.
4. The method of claim 1 , further comprising prior to step (a):
(a1) forming a reaction mixture comprising an oxidizing agent and a compound having the structure:
under conditions suitable to prepare the compound having the structure:
5. The method of claim 4 , wherein the oxidizing agent comprises hydrogen peroxide, NaW 2 O 4 and acetic acid.
6. The method of claim 4 , further comprising prior to step (a1):
(a2) forming a reaction mixture comprising ammonia, a non-nucleophilic base, and a compound having the structure:
under conditions suitable to form a compound having the structure:
followed by addition to the reaction mixture of a compound having the structure:
under conditions suitable to form the compound having the structure:
7. The method of claim 6 , wherein the non-nucleophilic base comprises triethylamine.
8. A method of preparing a compound, comprising:
(a) forming a first reaction mixture comprising ammonia and a compound having the structure:
under conditions suitable to form a compound having the structure:
followed by adding to the reaction mixture diisopropylethylamine and a compound having the structure:
under conditions suitable to form the compound having a structure:
(b) forming a second reaction mixture comprising peracetic acid and the compound produced in step (a), under conditions suitable to form a compound having the structure:
(c) forming a third reaction mixture comprising 1-butanol and the compound produced in step (b), under conditions suitable to form a compound having the structure:
(d) forming a fourth reaction mixture comprising Pd/C, hydrogen, and the compound produced in step (c), under conditions suitable to prepare a compound having the structure:
(e) forming a fifth reaction mixture comprising Raney Ni, formic acid, and the compound produced in step (d), under conditions suitable to prepare a compound having the structure:
(f) forming a sixth reaction mixture comprising NaBH(OAc) 3 , acetic acid, H—NR 6 R 7 and the compound produced in step (e), under conditions suitable to prepare the compound having the structure:
wherein
R 6 and R 7 , taken together with the nitrogen to which they are both attached, form a substituted or unsubstituted 4-6 membered heterocycle comprising 0 to 2 heteroatoms selected from N, O, or S.