Thionyl Chloride → 1H-indole-2-carbonyl Chloride
Reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([O-:12])=O.ClCl.S(Cl)([Cl:17])=O.P(Cl)(Cl)(Cl)=O.C(Cl)(=O)C(Cl)=O>>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([Cl:17])=[O:12]Participants
Procedure
In step 1 of Scheme A, bromobenzaldehyde compound a is reacted with azido ester b under basic conditions to yield indole 2-carboxylate ester c. Compound c is then treated in step 2 with benzyl compound d in the presence of alkali metal hydride to afford 1-benzyl indole compound e. In step 3 a Buchwald reaction is carried out by reaction of compound e with protected piperazine f (other cyclic amine may be used) in the presence of suitable catalyst to provide piperazinyl indole g. The ester portion of compound g is hydrolized under basic conditions in step 4 to afford indole-2-carboxylate compound h. In step 5, indole-2-carboxylate compound h is reacted with a chlorine agent such as thionyl chloride, phosphorus oxychloride of oxalyl chloride, to afford indole-2-carboxylic acid chloride compound i. In step 6 acid chloride compound i is reacted with amine i to afford indole-2-carboxamide compound k. Compound k is then deprotected in step 7 to afford compound m, which is a compound of formula I in accordance with the invention.
Sources & evidence
- ORD record
- ord-613a44b110af447e935fd8db0053c225
- Source dataset
- uspto-grants-2010_06
- Patent number
- US07741326B2
Reaction notes
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