Pyrrolo [3,2-b]pyridine processes and intermediates
AssigneeEli Lilly and Company
InventorsVincent Mancuso, Freddy Andre Napora, Uko Effiong Udodong, Daniel Edward Verral, II
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Abstract
The present invention provides processes and intermediates of Formula I: ##STR1## where X and R are defined in the specification, for the preparation of 5-amino-3-(1-methylpiperidin-4-yl)pyrrolo-[3,2-b]pyridine.
Claims21
A process for the preparation of 5-amino-3-(1-methylpiperidin-4-yl)pyrrolo-[3,2-b]pyridine (A), comprising the steps of:
- i) condensing 1-hydroxy-5-(dimethylaminomethyleneimino)pyrrolo[3,2-b]pyridine (F) with 1-methyl-4-piperidinone in the presence of a base to provide 1-hydroxy-5-(dimethylaminomethyleneimino)-3-(1-methyl-1,2,3,6-tetrahydropy ridin-4-yl)pyrrolo[3,2-b]pyridine (J);
- ii) optionally deprotecting (J) to provide 1-hydroxy-5-amino-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyrrolo-[3,2- b]pyridine (H);
- and
- iii) hydrogenating either (J) or (H).
A process for the preparation of 5-amino-3-(1-methylpiperidin-4-yl)pyrrolo[3,2-b]pyridine (A) comprising the steps of:
- i) condensing 1-hydroxy-5-aminopyrrolo[3,2-b ]-pyridine (G) with 1-methyl-4-piperidinone in the presence of a base to provide 1-hydroxy-5-amino-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyrrolo[3,2-b ]pyridine (H);
- and
- ii) hydrogenating (H).
A process for the preparation of 5-amino-3-(1-methylpiperidin-4-yl)pyrrolo[3,2-b]pyridine (A), comprising the steps of:
- i) nitrating 6-amino-2-picoline to provide a mononitrated 6-amino-2-picoline consisting of a mixture of 3-nitro- and 5-nitro-6-amino-2-picoline (B);
- ii) optionally separating the mixture of 3-nitro- and 5-nitro-6-amino picoline to provide a mononitrated 6-amino-2-picoline consisting of substantially pure 3-nitro-6-amino-2-picoline (C);
- iii) reacting a mononitrated 6-amino-2-picoline selected from (B) or (C) with a dimethylaminoformylating agent to provide 2-(2-dimethylaminoethen-1-yl)-3-nitro-6-(dimethylaminomethyleneimino)pyrid ine (E);
- iv) hydrogenating (E) in the presence of acid to provide 1-hydroxy-5-dimethylaminomethyleneiminopyrrolo[3,2-b]pyridine (F);
- v) reacting (F) with 1-methyl-4-piperidinone in the presence of a base to provide 1-hydroxy-5-(dimethylaminomethyleneimino)-3-(1-methyl-1,2,3,6-tetrahydropy ridin-4-yl)pyrrolo[3,2-b]pyridine (J);
- vi) optionally deprotecting (J) to provide 1-hydroxy-5-amino-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyrrolo-[3,2- b]pyridine (H);
- and
- vii) hydrogenating either (J) or (H).
A process for the preparation of 1-hydroxy-5-dimethylaminomethyleneiminopyrrolo[3,2-b]pyridine (F), comprising the steps of:
- i) nitrating 6-amino-2-picoline to provide a mononitrated 6-amino-2-picoline consisting of a mixture of 3-nitro- and 5-nitro-6-amino-2-picoline (B);
- ii) optionally separating the mixture of 3-nitro- and 5-nitro-6-amino picoline to provide a mononitrated 6-amino-2-picoline consisting of substantially pure 3-nitro-6-amino-2-picoline (C);
- iii) reacting a mononitrated 6-amino-2-picoline selected from (B) or (C) with a dimethylaminoformylating agent to provide 2-(2-dimethylaminoethen-1-yl)-3-nitro-6-(dimethylaminomethyleneimino)pyrid ine (E);
- iv) hydrogenating (E) in the presence of acid.
A 1-hydroxypyrrolo[3,2-b]pyridine of Formula I:
- ##STR6## where:
- X is amino or (CH.sub.3).sub.2 NCH.dbd.N--;
- and
- R is hydrogen or 1-methyl-1,2,3,6-tetrahydropyridin-4-yl;
- or an acid addition salt thereof.
Dependencies are inferred from the claim text.