Process for the preparation of 2-substituted-7-Boryl indoles and compounds
AssigneeBoard of Trustees of Michigan State University
InventorsMilton R. Smith, Robert E. Maleczka, Ghayoor Chotana, Sulagna Paul
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Abstract
Process for the preparation of 2-substituted-7-boryl indoles and compounds therefrom. The compounds are intermediates to functionalized indoles, both natural and synthetic which are cytotoxic agents, anticancer and antiviral agents.
Claims14
A process for producing a 2-substituted-7-boryl indole (I), which comprises:
- (a) reacting an indole (II) with an unprotected ring nitrogen in a reaction mixture with a non-reactive solvent, selected from, but not limited to, aliphatic hydrocarbons and ethers at temperatures between about 0 and 150° C. with an HB or B-B organic compound, in the presence of a catalytically effective amount of an iridium complex catalytic composition comprising an iridium complex of the formula:
- (BY)n—Ir-(ligand)m where n is equal to one to five and m is equal to one to three, excluding hydrogen, bonded to the iridium, BY is a boron moiety and the ligand is selected from the group consisting of a phosphorus organic ligand, an organic amine, an imine, a nitrogen heterocycle, and an ether wherein the ligand is at least in part bonded to the iridium, to form the 2-substituted-7-boryl indole (I) in the reaction mixture;
- and
- (b) evaporating the solvent and portions of the reaction mixture which are volatile from the reaction mixture to produce the 2-substituted-7-boryl indole (I).
A process for producing a 2-substituted-7-boryl indole (I), which comprises:
- (a) reacting an indole (II) with an unprotected ring nitrogen with an HB or B-B organic compound in a reaction mixture with a non-reactive first solvent selected from, but not limited to, aliphatic hydrocarbons and ethers at elevated temperatures between about 0 and 150° C. in the presence of a catalytically effective amount of an iridium complex catalytic composition comprising an iridium complex of the formula:
- (BY)n—Ir-(ligand)m where n is equal to one to five and m is equal to one to three, excluding hydrogen, bonded to the iridium, BY is a boron moiety and the ligand is selected from the group consisting of a phosphorus organic ligand, an organic amine, an imine, a nitrogen-heterocycle, and an ether wherein the ligand is at least in part bonded to the iridium, in a molar ratio of complex to ligand between 1 to 3 and 1 to 1, wherein the ligand is at least in part bonded to the iridium, to form the 2-substituted-7-boryl indole (I);
- (b) evaporating the first solvent and portions of the reaction mixture which are volatile from the reaction mixture;
- (c) dissolving the 2-substituted-7-boryl indole in a second solvent;
- and
- (d) isolating the 2-substituted-7-boryl indole (I) from the second solvent.
A 2-substituted-7-boryl indole (I) with an unprotected ring nitrogen, wherein there is at least one ring substituent in the 2 position other than hydrogen selected from the group consisting of boryl, halo, cyano, alkyl, alkoxy, thioalkyl, amino alkyl, acyl, alkyl aminoacyl, trifluoro alkyl, aryl, alkyl silyl, and containing 1 to 8 carbon atoms except for the halo group and boryl group and the boryl group is derived from HBPin or B2Pin.
A process for producing 2-substituted-7-boryl indole (I), which comprises:
- (a) reacting an indole (II) with an unprotected ring nitrogen with HBPin or B2Pin2, in a reaction mixture with a non-reactive first solvent selected from, but not limited to, aliphatic hydrocarbons and ethers at elevated temperatures between about 0 and 150° C. in the presence of a catalytically effective amount of an iridium complex catalytic composition comprising an iridium complex of the formula:
- (BY)n—Ir-(ligand)m where n is equal to one to five and m is equal to one to three, excluding hydrogen, bonded to the iridium BY is a boron moiety and the ligand is selected from the group consisting of a phosphorus organic ligand, an organic amine, an imine, a nitrogen heterocycle, and an ether wherein the ligand is at least in part bonded to the iridium, in a molar ratio of complex to ligand between 1 to 3 and 1 to 1, and wherein the ligand is at least in part bonded to the iridium, to form the 2-substituted-7-boryl indole (I) in the reaction mixture;
- and
- (b) evaporating the solvent and portions of the reaction mixture which are volatile from the reaction mixture to produce the 2-substituted-7-boryl indole (I).
Dependencies are inferred from the claim text.