Processes for preparation of 4-aminoindane compounds and related aminoindane amides
A process for preparation of 4-aminoindane compounds of a first formula, salts and enantiomers thereof including: a) hydrogenating a 1,2-dihydroquinoline of a second formula to give a corresponding tetrahydroquinoline of a third formula; b) acylating the tetrahydroquinoline of the third formula with a carboxylic acid derivative of a fourth formula to obtain a corresponding acyl derivative compound of a fifth formula; c) rearranging the acyl derivative compound of the fifth formula under acidic conditions so as to give an acyl indane compound of a sixth formula or an addition salt thereof; and d) hydrolysing the acyl group of the acyl indane compound of the sixth formula so as to obtain the 4-aminoindane derivatives of the first formula.
1. A process for preparation of 4-aminoindane compounds of Formula (I), salts and enantiomers thereof
comprising the steps of:
a) hydrogenating a 1,2-dihydroquinoline of Formula (IV)
to give a corresponding tetrahydroquinoline of Formula (V)
b) acylating the tetrahydroquinoline of Formula (V) with a carboxylic acid derivative of Formula RC(O)LG to obtain a corresponding acyl derivative compound of Formula (VI)
c) forming a slurry containing an organic solvent and the acyl derivative compound of Formula (VI);
d) feeding the slurry containing the organic solvent and the acyl derivative compound of Formula (VI) to step (e);
e) rearranging the acyl derivative compound of Formula (VI) under acidic conditions so as to give an acyl indane compound of Formula (VII) or an addition salt thereof
f) hydrolyzing the acyl group of the acyl indane compound of Formula (VII) so as to obtain the 4-aminoindane compounds of Formula (I) salts and enantiomers thereof;
wherein in the formulae:
n is an integer selected within the range from 0 to 3, inclusive;
R is a C 1 -C 6 alkyl group or a C 6 -C 10 aryl group, these groups being optionally substituted with one or more of: C 1 -C 6 alkyl groups or halogen atoms; and
LG is a leaving group selected from: (i) a hydroxy group; (ii) a halogen atom; (iii) a C 1 C 6 alkylsulfonyloxy group; (iv) a C 6 -C 10 arylsulfonyloxy group; or (v) a R a COO group wherein R a is a C 1 -C 6 alkyl group, the groups (iii)-(v) being optionally substituted with one or more halogen atoms.
2. The process of claim 1 , wherein step (a) comprises:
dissolving the 1,2-dihydroquinoline of Formula (IV) in an organic solvent; and
contacting the 1,2-dihydroquinoline of Formula (IV) dissolved in the organic solvent with gaseous hydrogen in the presence of a hydrogenation catalyst so as to obtain the tetrahydroquinoline of Formula (V).
3. The process of claim 1 , wherein step (a) comprises:
dissolving the 1,2-dihydroquinoline of Formula (IV) in a polar solvent; and
contacting the 1,2-dihydroquinoline of Formula (IV) dissolved in the polar solvent w gaseous hydrogen in the presence of a hydrogenation catalyst so as to obtain the tetrahydroquinoline of Formula (V).
4. The process of claim 1 , wherein the carboxylic acid derivative of Formula RC(O)LG is selected from acetyl chloride, acetic anhydride, or mixtures thereof.
5. The process of claim 1 , wherein step (b) is carried out in the absence of added solvent.
6. The process of claim 1 , wherein step ( 1 ) comprises contacting the acyl indane compound of Formula (VII) with water.
7. The process of claim 1 , wherein the organic solvent is selected from: aliphatic or cycloaliphatic hydrocarbons, chlorinated hydrocarbons, aromatic hydrocarbons, alcohols, glycols, esters, or mixtures thereof.
8. The process of claim 1 , wherein the organic solvent is selected from: hexane, heptane, methylene chloride, dichloroethane, methanol, ethanol, isopropanol, toluene, ethyl acetate, or mixtures thereof.
9. A process for preparation of 4-aminoindane compounds of Formula (I), salts and enantiomers thereof
comprising the steps of:
a) hydrogenating a 1,2-dihydroquinoline of Formula (IV)
to give a corresponding tetrahydroquinoline of Formula (V)
b) acylating the tetrahydroquinoline of Formula (V) with a carboxylic acid derivative of Formula RC(O)LG to obtain a corresponding acyl derivative compound of Formula (VI)
c) rearranging the acyl derivative compound of Formula (VI) under acidic conditions so as to give an acyl indane compound of Formula (VII) or an addition salt thereof
d) forming a slurry comprising an organic solvent and the acyl indane compound of Formula (VII) in a form of an addition salt;
e) feeding the slurry containing the organic solvent and the acyl indane compound of Formula (VII), in the form of the addition salt, to step (f);
f) hydrolyzing the acyl group of the acyl indane compound of Formula (VII) so as to obtain the 4-aminoindane compounds of Formula (I), salts and enantiomers thereof;
wherein in the formulae:
n is an integer selected within the range from 0 to 3, inclusive;
R is a C 1 -C 6 alkyl group or a C 6 -C 10 aryl group, these groups being optionally substituted with one or more of: C 1 -C 6 alkyl groups or halogen atoms; and
LG is a leaving group selected from: (i) a hydroxy group; (ii) a halogen atom; (iii) a C 1 -C 6 alkylsulfonyloxy group; (iv) a C 6 -C 10 arylsulfonyloxy group; or (v) a R a COO group wherein R a is a C 1 -C 6 alkyl group, the groups (iii)-(v) being optionally substituted with one or more halogen atoms.
10. The process of claim 9 , wherein step (a) comprises:
dissolving the 1,2-dihydroquinoline of Formula (IV) in an organic solvent; and
contacting the 1,2-dihydroquinoline of Formula (IV) dissolved in the organic solvent with gaseous hydrogen in the presence of a hydrogenation catalyst so as to obtain the tetrahydroquinoline of Formula (V).
11. The process of claim 9 , wherein step (a) comprises:
dissolving the 1,2-dihydroquinoline of Formula (IV) in a polar solvent; and
contacting the 1,2-dihydroquinoline of Formula (IV) dissolved in the polar solvent with gaseous hydrogen in the presence of a hydrogenation catalyst so as to obtain the tetrahydroquinoline of Formula (V).
12. The process of claim 9 , wherein the carboxylic acid derivative of Formula RC(O)LG is selected from acetyl chloride, acetic anhydride, or mixtures thereof.
13. The process of claim 9 , wherein step (b) is carried out in the absence of added solvent.
14. The process of claim 9 , wherein step (f) comprises contacting the acyl indane compound of Formula (VII) with water.
15. The process of claim 9 , wherein the organic solvent is selected from: aliphatic or cycloaliphatic hydrocarbons, chlorinated hydrocarbons, aromatic hydrocarbons, alcohols, glycols, esters, or mixtures thereof.
16. The process of claim 9 , wherein the organic solvent is selected from: hexane, heptane, methylene chloride, dichloroethane, methanol, ethanol, isopropanol, toluene, ethyl acetate, or mixtures thereof.
17. A process for preparation of 4-aminoindane compounds of Formula (I), salts and enantiomers thereof
comprising the steps of:
a) hydrogenating a 1,2-dihydroquinoline of Formula (IV)
to give a corresponding tetrahydroquinoline of Formula (V)
b) acylating the tetrahydroquinoline of Formula (V) with a carboxylic acid derivative of Formula RC(O)LG to obtain a corresponding acyl derivative compound of Formula (VI)
c) rearranging the acyl derivative compound of Formula (VI) under acidic conditions so as to give an acyl indane compound of Formula (VII) or an addition salt thereof
d) hydrolyzing the acyl group of the acyl indane compound of Formula (VII) so as to obtain the 4-aminoindane compounds of Formula (I), salts and enantiomers thereof;
wherein in the formulae:
n is an integer selected within the range from 0 to 3, inclusive;
R is a C 1 -C 6 alkyl group or a C 6 -C 10 aryl group, these groups being optionally substituted with one or more of: C 1 -C 6 alkyl groups or halogen atoms; and
LG is a leaving group selected from: (i) a hydroxy group; (ii) a halogen atom; (iii) a C 1 -C 6 alkylsulfonyloxy group; (iv) a C 6 -C 10 arylsulfonyloxy group; or (v) a R a COO group wherein R a is a C 1 -C 6 alkyl group, the groups (iii)-(v) being optionally substituted with one or more halogen atoms; and
wherein the acyl indane compound of Formula (VII) in a form of an addition salt is contacted with an alkaline aqueous solution so as to obtain the 4-aminoindane compounds of Formula (I), salts and enantiomers thereof.
18. The process of claim 17 , wherein step (a) comprises:
dissolving the 1,2-dihydroquinoline of Formula (IV) in an organic solvent; and
contacting the 1,2-dihydroquinoline of Formula (IV) dissolved in the organic solvent with gaseous hydrogen in the presence of a hydrogenation catalyst so as to obtain the tetrahydroquinoline of Formula (V).
19. The process of claim 17 , wherein step (a) comprises:
dissolving the 1,2-dihydroquinoline of Formula (IV) in a polar solvent; and
contacting the 1,2-dihydroquinoline of Formula (IV) dissolved in the polar solvent with gaseous hydrogen in the presence of a hydrogenation catalyst so as to obtain the tetrahydroquinoline of Formula (V).
20. The process of claim 17 , wherein the carboxylic acid derivative of Formula RC(O)LG is selected from acetyl chloride, acetic anhydride, or mixtures thereof.
21. The process of claim 17 , wherein step (b) is carried out in the absence of added solvent.
22. The process of claim 17 , wherein step (d) comprises contacting the acyl indane compound of Formula (VII) with water.
23. The process of claim 17 , wherein step (c) further comprises suspending the acyl derivative compound of Formula (VI) in an organic solvent, and
wherein the organic solvent is selected from: aliphatic or cycloaliphatic hydrocarbons, chlorinated hydrocarbons, aromatic hydrocarbons, alcohols, glycols, esters, or mixtures thereof.
24. The process of claim 23 , wherein the organic solvent is selected from: hexane, heptane, methylene chloride, dichloroethane, methanol, ethanol, isopropanol, toluene, ethyl acetate, or mixtures thereof.