Production method of thiazole derivative
Provided is a production method of a thiazole derivative represented by the formula (I), which has an adenosine A 2A receptor antagonistic action and is useful as a therapeutic agent for, for example, Parkinson's disease, sleep disorder, analgesic resistance to opioid, migraine, movement disorder, depression, anxiety disorder and the like. Also provided is a production method of a compound represented by the formula (C), which contains (i) a step of reacting a compound represented by the formula (A) and a compound represented by the formula (B), and the like: (wherein R 1 represents furyl, R 4 , R 5 and R 6 are the same or different and each represents lower alkyl or aryl, R 2 represents pyridyl or tetrahydropyranyl, and X 1 represents halogen).
1. A production method of a compound represented by formula (C), comprising a step (i) of reacting a compound represented by formula (A) and a compound represented by formula (B):
where R 1 represents furyl, R 4 , R 5 and R 6 independently represent lower alkyl or aryl, R 2 represents pyridyl or tetrahydropyranyl, and X 1 represents halogen.
2. The production method according to claim 1 , wherein X 1 is a chlorine atom, a bromine atom or an iodine atom.
3. The production method according to claim 1 , wherein X 1 is a bromine atom.
4. The production method according to claim 1 , wherein R 4 , R 5 and R 6 are each methyl.
5. The production method according to claim 1 , wherein R 1 is 2-furyl.
6. The production method according to claim 1 , further comprising a step of reacting the compound according to formula (C) to obtain a compound represented by formula (I):
where R 3 represents aryl, aralkyl, an aromatic heterocyclic group, aromatic heterocyclylalkyl, aliphatic heterocyclylalkyl or tetrahydropyranyloxy, or these groups substituted by 1 to 3 substituents selected from the group consisting of halogen; lower alkyl optionally substituted by lower alkoxy or morpholino; lower alkoxy; lower alkanoyl; and vinyl.
7. The production method according to claim 6 , wherein said step of reacting the compound according to formula (C) to obtain said compound represented by formula (I) comprises:
a step (ii) of obtaining a compound represented by formula (D) by treating said compound represented by formula (C) with an acid:
and
a step (iii) of obtaining said compound represented by formula (I) by reacting said compound represented by formula (D) and a compound represented by formula (E):
where Y represents halogen or hydroxy.
8. The production method according to claim 7 , wherein the acid in step (ii) is hydrochloric acid or trifluoroacetic acid.
9. The production method according to claim 7 , wherein Y is hydroxy.
10. The production method according to claim 9 , wherein the reaction in step (iii) is performed in the presence of 1,3-dicyclohexylcarbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, 1,1′-carbonyldiimidazole (CDI) or propylphosphonic anhydride.
11. The production method according to claim 9 , wherein the reaction in step (iii) is performed in the presence of CDI.
12. The production method according to claim 1 , wherein R 2 is 4-tetrahydropyranyl.
13. The production method according to claim 6 , wherein R 3 is 2-methylpyridin-5-yl, 2-methylpyrimidin-5-yl, 5,6-dihydro-2H-pyridylmethyl or 4-tetrahydropyranyloxy.
14. The production method according to claim 6 , wherein R 3 is 2-methylpyridin-5-yl.
15. The production method according to claim 6 , wherein R 1 is 2-furyl, R 2 is 4-tetrahydropyranyl, and R 3 is 2-methylpyridin-5-yl.