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US 8,710,093 B2Granted
Synthesis of amines and intermediates for the synthesis thereof
AssigneeBASF SE Ludwigshafen
InventorsUlrich Berens, Oliver Dosenbach, Daniel Sprenger
Life of this patent
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Abstract
The invention relates in a first embodiment to a method for the manufacture of esters of the formula I, or especially of amides of the formula II, wherein the symbols have the meanings given in the specification, as well as other intermediates and compounds useful in the synthesis of tryptamines and other substances mentioned in the title. The synthesis methods and intermediates are useful in the synthesis of pharmaceuticals.
Claims10
A compound or a salt thereof of formula II shown below
- wherein
- n is a number from 0 to 4,
- each R1 is, independently of the other substituents R1, is unsubstituted or substituted alkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl, alkylsulfonyl, sulfonyl alkyl, N-mono- or N,N-disubstituted or unsubstituted aminosulfonyl alkyl, hydroxy, mercapto, nitro, halogen, cyano, carboxamido, N-mono- or N,N-disubstituted carboxamido, carboxhydrazido, unsubstituted or substituted alkoxycarbonyl, unsubstituted or substituted alkoxy, formyl or other alkanoyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, alkanoyloxy, N-mono- or N,N-disubstituted or unsubstituted amino, unsubstituted or substituted hydrazino, or is a residue of a boronic acid or an ester thereof,
- R2 is hydrogen or unsubstituted or substituted alkyl, unsubstituted or substituted alkoxycarbonyl, unsubstituted or substituted arylsulfonyl, unsubstituted or substituted alkylsulfonyl, unsubstituted or substituted aryl, carbamoyl or N-mono- or N,N-disubstituted carbamoyl, silyl substituted by three moieties independently selected from unsubstituted or substituted alkyl and substituted or unsubstituted aryl, or acyl, and
- R3 and R4 are, independently of each other, unsubstituted or substituted alkyl or together form an unsubstituted or substituted alkylene bridge (thus forming a ring with the binding nitrogen) or an alkylene bridge to which a phenyl or a C3-C8-cycloalkyl ring is condensed at two vicinal carbon atoms of the alkylene bridge.
2 more elements
A method for the manufacture of a compound of the formula I or II defined below, comprising a method for the manufacture of esters of the formula I,
- wherein n is a number from 0 to 4,
- each R1 is, independently of the other substituents R1, unsubstituted or substituted alkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl, alkylsulfonyl, sulfonyl alkyl, N-mono- or N,N-disubstituted or unsubstituted aminosulfonyl alkyl, hydroxy, mercapto, nitro, halogen, cyano, carboxamido, N-mono- or N,N-disubstituted carboxamido, carboxhydrazido, unsubstituted or substituted alkoxycarbonyl, unsubstituted or substituted alkoxy, formyl or other alkanoyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, alkanoyloxy, N-mono- or N,N-disubstituted or unsubstituted amino, unsubstituted or substituted hydrazino, or is a residue of a boronic acid or an ester thereof;
- R2 is hydrogen or unsubstituted or substituted alkyl, unsubstituted or substituted alkoxycarbonyl, unsubstituted or substituted arylsulfonyl, unsubstituted or substituted alkylsulfonyl, unsubstituted or substituted aryl, carbamoyl or N-mono- or N,N-disubstituted carbamoyl, silyl substituted by three moieties independently selected from unsubstituted or substituted alkyl and substituted or unsubstituted aryl, or acyl, and
- R′ is unsubstituted or substituted alkyl,
- or of amides of the formula II,
- wherein n, R1 and R2 are as defined under formula I and R3 and R4 are, independently of each other, unsubstituted or substituted alkyl or together form an unsubstituted or substituted alkylene bridge (thus forming a ring with the binding nitrogen) or an alkylene bridge to which a phenyl or a C3-C8-cycloalkyl ring is condensed at two vicinal carbon atoms of the alkylene bridge
- where a starting material of the formula III,
- wherein n, R1 and R2 have the meanings given under formula I and NB is a tertiary nitrogen base where the nitrogen is not part of a ring,
- is reacted
- (a) for the synthesis of an ester of the formula I with an active carbonic ester of the formula IV,
- wherein X is halogen and R′ is as defined under formula I, to give the corresponding ester of the formula I, or
- (b) for the synthesis of an amide of the formula II with an active amido carbonic acid derivative of the formula V,
- wherein X is halogen and R3 and R4 are as defined under formula II, to give the corresponding compound of the formula II,
- where in a further step an amide of the formula II wherein n is zero and thus R1 is absent is converted to a compound of the formula VII,
- wherein Ac is acetyl and R2, R3 and R4 have the meanings indicated for compounds of the formula II with the proviso that in the compound of the formula II and of the formula VII, R2 is other than hydrogen;
- by the reaction with formaldehyde or a precursor thereof in the presence of acetic acid, and
- transforming the compound of the formula VII
- into the corresponding free alcohol of the formula VIII,
- wherein R2, R3 and R4 are as defined under formula VII.
16 more elements
A method for the manufacture of a compound of the formula I or II defined below, comprising a method for the manufacture of esters of the formula I,
- wherein n is a number from 0 to 4,
- each R1 is, independently of the other substituents R1, unsubstituted or substituted alkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl, alkylsulfonyl, sulfonyl alkyl, N-mono- or N,N-disubstituted or unsubstituted aminosulfonyl alkyl, hydroxy, mercapto, nitro, halogen, cyano, carboxamido, N-mono- or N,N-disubstituted carboxamido, carboxhydrazido, unsubstituted or substituted alkoxycarbonyl, unsubstituted or substituted alkoxy, formyl or other alkanoyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, alkanoyloxy, N-mono- or N,N-disubstituted or unsubstituted amino, unsubstituted or substituted hydrazino, or is a residue of a boronic acid or an ester thereof;
- R2 is hydrogen or unsubstituted or substituted alkyl, unsubstituted or substituted alkoxycarbonyl, unsubstituted or substituted arylsulfonyl, unsubstituted or substituted alkylsulfonyl, unsubstituted or substituted aryl, carbamoyl or N-mono- or N,N-disubstituted carbamoyl, silyl substituted by three moieties independently selected from unsubstituted or substituted alkyl and substituted or unsubstituted aryl, or acyl, and
- R′ is unsubstituted or substituted alkyl,
- or of amides of the formula II,
- wherein n, R1 and R2 are as defined under formula I and R3 and R4 are, independently of each other, unsubstituted or substituted alkyl or together form an unsubstituted or substituted alkylene bridge (thus forming a ring with the binding nitrogen) or an alkylene bridge to which a phenyl or a C3-C8-cycloalkyl ring is condensed at two vicinal carbon atoms of the alkylene bridge
- where a starting material of the formula III,
- wherein n, R1 and R2 have the meanings given under formula I and NB is a tertiary nitrogen base where the nitrogen is not part of a ring,
- is reacted
- (a) for the synthesis of an ester of the formula I with an active carbonic ester of the formula IV,
- wherein X is halogen and R′ is as defined under formula I, to give the corresponding ester of the formula I, or
- (b) for the synthesis of an amide of the formula II with an active amido carbonic acid derivative of the formula V,
- wherein X is halogen and R3 and R4 are as defined under formula II, to give the corresponding compound of the formula II,
- wherein an amide compound of the formula II wherein R2 has one of the meanings given above other than hydrogen is further reacted with a dehydrating agent to give a compound of the formula Xa,
- wherein n and R1 are as defined under formula I and R3 and R4 are, independently of each other, unsubstituted or substituted alkyl, or together form an unsubstituted or substituted alkylene bridge, and
- reducing the compound of the formula Xa in the presence of a reductant to a compound of the formula Xb,
- wherein n, R1, R2, R3 and R4 are defined above.
14 more elements
A method for the manufacture of a compound of the formula I or II defined below, comprising a method for the manufacture of esters of the formula I,
- wherein n is a number from 0 to 4,
- R1 is unsubstituted or substituted alkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl, alkylsulfonyl, sulfonyl alkyl, N-mono- or N,N-disubstituted or unsubstituted aminosulfonyl alkyl, hydroxy, mercapto, nitro, halogen, cyano, carboxamido, N-mono- or N,N-disubstituted carboxamido, unsubstituted or substituted alkoxycarbonyl, unsubstituted or substituted alkoxy, formyl or other alkanoyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, alkanoyloxy, N-mono- or N,N-disubstituted or unsubstituted amino, or is a residue of a boronic acid or an ester thereof,
- R2 is hydrogen or unsubstituted or substituted alkyl, unsubstituted or substituted alkoxycarbonyl, unsubstituted or substituted arylsulfonyl, unsubstituted or substituted alkylsulfonyl, unsubstituted or substituted aryl, carbamoyl or N-mono- or N,N-disubstituted carbamoyl, silyl substituted by three moieties independently selected from unsubstituted or substituted alkyl and substituted or unsubstituted aryl, or acyl, and
- R′ is unsubstituted or substituted alkyl,
- or of amides of the formula II,
- wherein n, R1 and R2 are as defined under formula I and R3 and R4 are, independently of each other, unsubstituted or substituted alkyl or together form an unsubstituted or substituted alkylene bridge (thus forming a ring with the binding nitrogen) or an alkylene bridge to which a phenyl or a C3-C8-cycloalkyl ring is condensed at two vicinal carbon atoms of the alkylene bridge
- where a starting material of the formula III,
- wherein n, R1 and R2 have the meanings given under formula I and NB is a tertiary nitrogen base where the nitrogen is not part of a ring,
- is reacted
- (a) for the synthesis of an ester of the formula I with an active carbonic ester of the formula IV,
- wherein X is halogen and R′ is as defined under formula I, to give the corresponding ester of the formula I, or
- (b) for the synthesis of an amide of the formula II with an active amido carbonic acid derivative of the formula V,
- wherein X is halogen and R3 and R4 are as defined under formula II, to give the corresponding compound of the formula II,
- the method further comprising reducing a compound of the formula II
- wherein n, R1, R2, R3 and R4 are, independently of each other, as defined above,
- in the presence of a complex hydride.
13 more elements
Dependencies are inferred from the claim text.