Synthesis of 5 substituted 7-azaindoles and 7-azaindolines
View Patent ↗The present invention provides a novel substituted azaindoline intermediate of formula (I) and a method for its synthesis. The novel substitued azaindoline intermediate (I) is provided for use in the manufacture of 5-substituted 7-azaindolines and 5-substituted 7-azaindoles.
1. A compound of formula (I)
wherein X is R 1 S(O) 2 , (R 1 ) 3 Si, R 1 C(O), R 1 OCH 2 , R 1 2 NSO 2 , R 1 OC(O)—, R 1 (R 1 O)CH—, R 1 CH 2 CH 2 —, R 1 CH 2 —, PhC(O)CH 2 —, CH 2 ═CH—, ClCH 2 CH 2 —, Ph 3 C—, Ph 2 (4-pyridyl)C—, Me 2 N—, HO—CH 2 —, R 1 OCH 2 —, (R 1 ) 3 SiOCH 2 —, (R 1 O) 2 CH—, t-BuOC(O)CH 2 —, Me 2 NCH 2 — and tetrahydropyranylamine;
wherein R 1 is C 1-6 alkyl, C 3-12 cycloalkyl, C 1-6 haloalkyl, or C 6-12 carbocyclyl; optionally substituted with one or more of C 1-6 alkyl, Si(R 3 ) 3 , OR 3 , NO 2 , CO 2 , CO 2 R 3 , halogen, haloalkyl, SR 3 , CN, NR 3 COR 3 , COR 13 CONR 3 R 3 ,
wherein R 3 is hydrogen or C 1-6 alkyl,
with the proviso that when X is R 1 OC(O)—, R 1 is not PhCH 2 .
2. The compound of claim 1 , wherein X is (R 1 ) 3 Si or R 1 OCH 2 , and R 1 is C 1-6 alkyl or C 6-12 aryl.
3. The compound of claim 1 , wherein X is (R 1 ) 3 Si and R 1 is methyl, ethyl, propyl, butyl or phenyl.
4. The compound of claim 1 , wherein X is TBS.
5. The compound of claim 1 , wherein X is PhSO 2 .
6. A method for synthesizing a compound of formula (I) as claimed in claim 2 , comprising brominating a compound of formula (II);
wherein X is (R 1 ) 3 Si or R 1 OCH 2 , and R 1 is C 1-6 alkyl or C 6-12 aryl.
7. A method as claimed in claim 6 wherein the bromination is carried out using Br 2 , dioxane dibromide, pyridinium perbromide or NBS.
8. A method as claimed in claim 6 wherein X is (R 1 ) 3 Si and R 1 is methyl, ethyl, propyl, butyl or phenyl.
9. A method as claimed in claim 7 wherein X is (R 1 ) 3 Si and R 1 is methyl, ethyl, propyl, butyl or phenyl.