PROCESS FOR PREPARING PYRANOINDAZOLE SEROTONERGIC RECEPTOR AGONISTS
Described are methods of making pyranoindazoles comprising reacting with a reducing agent a protected halohydrin comprising a secondary carbamate to form a pyranoindazole. In preferred embodiments the secondary carbamate is a benzyl carbamate. Also preferred are embodiments wherein the reacting is preceded by reacting a protected halohydrin with a first organometallic compound. The pyranoindazoles thus formed by the described methods are preferably pharmaceutically active products.
1 . A method of making a pyranoindazole comprising:
reacting with a reducing agent a protected halohydrin comprising a secondary carbamate to form a pyranoindazole.
2 . The method of claim 1 further comprising the step of:
converting the pyranoindazole via hydrogenolysis to form a pyranoindazole having a primary amino group.
3 . The method of claim 1 wherein said reacting is preceded by reacting said protected halohydrin with a first organometallic compound.
4 . The method of claim 3 wherein said reducing agent is a second organometallic compound.
5 . The method of claim 3 wherein said first organometallic compound is a Grignard reagent.
6 . The method of claim 3 wherein said first organometallic compound is methylmagnesium chloride or ethylmagnesium chloride.
7 . The method of claim 1 wherein said reducing agent is n-butyllithium.
8 . The method of claim 1 wherein said reducing agent is an organometallic compound.
9 . The method of claim 1 wherein said secondary carbamate is a benzyl carbamate.
10 . A method of making (R)-1-((S)-2-aminopropyl)-1,7,8,9-tetrahydropyrano[2,3-g]indazol-8-ol comprising:
reacting a bromohydrin silyl ether comprising a benzyl carbamate with a reducing agent to form (R)-1-((S)-2-(benzyloxycarbonyl)aminopropyl)-1,7,8,9-tetrahydropyrano[2,3-g]indazol-8-ol;
converting (R)-1-((S)-2-(benzyloxycarbonyl)aminopropyl)-1,7,8,9-tetrahydropyrano[2,3-g]indazol-8-ol via hydrogenolysis to form (R)-1-((S)-2-aminopropyl)-1,7,8,9-tetrahydropyrano[2,3-g]indazol-8-ol.
11 . The method of claim 10 wherein said reducing agent is n-butyllithium.
12 . The method of claim 10 wherein said reacting is preceded by reacting said bromohydrin silyl ether with a Grignard reagent.
13 . The method of claim 12 wherein said Grignard reagent is methylmagnesium chloride or ethylmagnesium chloride.
14 . The method of claim 10 wherein said bromohydrin silyl ether is formed by:
forming a bromohydrin from an epoxide;
reacting said bromohydrin with a silane to form said bromohydrin silyl ether.
15 . A compound of Formula (I):