Method for synthesizing substituted aminocyclohexanone compounds
View Patent ↗A method of synthesizing a substituted aminocyclohexanone compound comprising reacting a compound of formula (II) with an organolithium compound to form a compound of formula (III)
1. A method of synthesizing a compound of formula (IV)
wherein
R 1 denotes —H or —CH 3 , and
R 2 denotes —H, —Cl or —F;
said method comprising reacting a compound of formula (II)
with an organolithium compound of formula (VII)
wherein
R 2 denotes —H, —Cl or —F;
to form a compound of formula (III)
optionally methylating the amino function to obtain a compound in which R 1 is CH 3 , and
cleaving the ketal function of the compound of formula (III) to convert the compound of formula (III) into the compound of formula (IV).
2. The method according to claim 1 , wherein R 2 denotes —H.
3. The method according to claim 1 , comprising forming the compound of formula (II) by first reacting a compound of formula (I)
with methylamine.
4. The method according to claim 1 , further comprising converting the compound of formula (III) into a hydrochloride salt.
5. The method according to claim 1 , further comprising converting a hydrochloride salt of a compound of formula (III) into a free base.
6. The method according to claim 1 , wherein the ketal function of the compound of formula (III) is cleaved to obtain a compound of formula (IVa)
7. The method according to claim 6 , further comprising converting the compound of formula (IVa) into a hydrochloride salt.
8. The method according to claim 6 , further comprising converting a hydrochloride salt of a compound of formula (IVa) into a free base.
9. The method according to claim 1 , wherein the amino function of the compound of formula (III) is methylated to obtain a compound of formula (V)
10. The method according to claim 9 , wherein the methylation is effected by reacting the compound of formula (III) with formaldehyde solution and formic acid.
11. The method according to claim 9 , wherein the ketal function of the compound of formula (V) is cleaved to obtain a compound of formula (IVb)
12. A method of synthesizing a compound of formula (VI)
wherein
R 1 denotes —H or —CH 3 ,
or a physiologically acceptable salt thereof,
said method comprising
reacting a compound of formula (II)
with an organolithium compound of formula (VII)
wherein
R 2 denotes —H, —Cl or —F;
to form a compound of formula (III)
optionally methylating the amino function to obtain a compound in which R 1 is CH 3 ;
cleaving the ketal function of the compound of formula (III) to convert the compound of formula (III) into a compound of formula (IV)
and
subjecting the compound of formula (IV) to an acid-catalysed Oxa-Pictet-Spengler reaction with a heteroaromatic compound to form the compound of formula (VI).