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US 11,739,062 B2Granted
Methods for 1,4-diazo N-heterocycle synthesis
AssigneePurdue Research Foundation
InventorsMingji Dai, Zhishi Ye
Life of this patent
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Abstract
The present disclosure relates to novel synthetic method of making 1, 4-diazo N-heterocycles via intermolecular amphoteric diamination of allenes, and to the compounds made by the novel synthetic method.
Claims5
A method of preparing a compound of formula II, wherein the method comprises a first step of reacting a compound of R1NHXNYR2 with a compound of CH2═C═CR3R4 to provide a compound of formula I:
- and
- a second step of a reduction reaction by converting the compound of formula I to the compound of formula II,
- wherein:
- R1 is R5—S(═O)2— or a nitrogen:
- protecting group selected from the group consisting of acetyl (Ac), trifluoroacetyl (TFA), trichloroacetyl (TCA), tert-butyloxycarbonyl (Boc), carbobenzyloxy (Cbz), vinyloxycarbonyl (Voc), allyloxycarbonyl (Alloc), and 9-fluorenylmethyloxycarbonyl (Fmoc);
- R2 is optionally substituted C1-C12 straight or branched alkyl, C1-C12 alkenyl, C1-C12 alkynyl, C3-C10 cycloalkyl, or C3-C10 hetero cycloalkyl, wherein one or more hydrogen is optionally substituted by an optionally substituted aryl, heteroaryl, C3-C10 cycloalkyl, C3-C10 hetero cycloalkyl, F, Cl, Br, I, hydroxyl, C1-C8 alkoxyl, amino group, or NHBoc, or R2 may form a fused ring with one adjacent carbon atom next to the nitrogen to which R2 is attached;
- R3 and R4 are each independently H, optionally substituted C1-C12 straight or branched alkyl, C1-C12 alkenyl, C1-C12 alkynyl, C3-C10 cycloalkyl, C3-C10 hetero cycloalkyl, or an electron-withdrawing group (EWG), wherein at least one of R3 and R4 is an EWG selected from the grout consisting of methoxycarbonyl, ethoxycarbonyl, butoxycarbonyl, t-butoxycarbonyl, phenoxycarbonyl, (3-methoxyphenoxy)carbonyl, ((3-methoxybenzyl)oxy)carbonyl, furan-2-carbonyl, benzoyl, fluorobenzoyl, chlorobenzoylmethoxybenzoyl, trifluoromethylbenzoyl, diethoxyphosphoryl, diphenylphosphoryl, phenylsulfonyl, cyano, and 2-oxy-4-phenylbutyl;
- R5 is optionally substituted C1-C12 straight or branched alkyl, C1-C12 alkenyl, C1-C12 alkynyl, C3-C10 cycloalkyl, C3-C10 hetero cycloalkyl, aryl, or heteroaryl;
- R6 is H, nitro, F, Cl, Br, I, amino, cyano, C1-C4 straight, branched, or cycloalkyl, C1-C4 trifluoroalkyl, hydroxyl, C1-C4 alkoxyl, or —SH;
- R7 is H or C1-C4 straight, branched, or cycloalkyl;
- X is a C2-C4 saturated carbon linker, wherein C2-C4 saturated carbon linker is optionally substituted with 4-8 hydrogen, 4-8 optionally substituted C1-C12 straight or branched alkyl, wherein one of the 4-8 optionally substituted C1-C12 straight or branched alkyl may form a fused ring with the C2-C4 saturated carbon linker or with R1, or form a spiro ring with the carbon atom on the C2-C4 saturated carbon linker to which the straight or branched alkyl is attached;
- and
- Y is H, Cl, Br, or I.
10 more elements
A method of preparing a compound of formula II, wherein the method comprises a first step of reacting a compound of R′NHXNYR2 with a compound of CH2═C═CR3R4 to provide a compound of formula I:
- and
- a second step of a reduction reaction by converting the compound of formula I to the compound of formula II,
- wherein:
- R1 is R5—S(═O)2— or a nitrogen-protecting group selected from the group consisting of acetyl (Ac), trifluoroacetyl (TFA), trichloroacetyl (TCA), tert-butyloxycarbonyl (Boc), carbobenzyloxy (Cbz), vinyloxycarbonyl (Voc), allyloxycarbonyl (Alloc), and 9-fluorenylmethyloxycarbonyl (Fmoc);
- R2 is optionally substituted C1-C12 straight or branched alkyl, C1-C12 alkenyl, C1-C12 alkynyl, C3-C10 cycloalkyl, or C3-C10 hetero cycloalkyl, wherein one or more hydrogen is optionally substituted by an optionally substituted aryl, heteroaryl, C3-C10 cycloalkyl, C3-C10 hetero cycloalkyl, F, Cl, Br, I, hydroxyl, C1-C8 alkoxyl, amino group, or NHBoc, or R2 may form a fused ring with one adjacent carbon atom next to the nitrogen that R2 is attached;
- R3 and R4 are each independently H, optionally substituted C1-C12 straight or branched alkyl, C1-C12 alkenyl, C1-C12 alkynyl, C3-C10 cycloalkyl, C3-C10 hetero cycloalkyl, or an electron-withdrawing group (EWG), wherein at least one of R3 and R4 is an EWG selected from the group consisting of an aldehyde group, a ketone group, a carboxylic acid group, an acyl group, an ester group, an amide group, a trihalide group, a sulfonyl group, a phosphono group, F, and Cl;
- R5 is optionally substituted C1-C12 straight or branched alkyl, C1-C12 alkenyl, C1-C12 alkynyl, C3-C10 cycloalkyl, C3-C10 hetero cycloalkyl, aryl, or heteroaryl;
- R6 is H, nitro, F, Cl, Br, I, amino, cyano, C1-C4 straight, branched, or cycloalkyl, C1-C4 trifluoroalkyl, hydroxyl, C1-C4 alkoxyl, or —SH;
- R7 is H or C1-C4 straight, branched, or cycloalkyl;
- X is a C2-C4 saturated carbon linker, wherein C2-C4 saturated carbon linker is optionally substituted with 4-8 hydrogen, 4-8 optionally substituted C1-C12 straight or branched alkyl, wherein one of the 4-8 optionally substituted C1-C12 straight or branched alkyl may form a fused ring with the C2-C4 saturated carbon linker or with R1, or form a spiro ring with the carbon atom on the C2-C4 saturated carbon linker to which the straight or branched alkyl is attached;
- and
- Y is H, Cl, Br, or I.
9 more elements
Dependencies are inferred from the claim text.