Substituted 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-3(2h)-ones and 2,5,6,7-tetrahydro-3h-pyrrolo[2,1-c][1,2,4]triazol-3-ones, and use thereof

2:

• The compound according to claim 1, wherein
• A is (C1-C4)-alkylene,
• wherein (C1-C4)-alkylene may be substituted by hydroxyl and methoxy and may be up to trisubstituted by fluorine
• or
• A is a group of the formula
• wherein
• n is 1,
• p is 0,
• q is 1,
• wherein
• #1 marks the bond to the nitrogen atom of the 5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl ring,
• marks the bond to R1;
• X is —CR6R7— or #2—CR6R7—CR8R9—**,
• wherein #2 marks the bond to the carbon atom of the CR4R5— group,
• wherein ** marks the bond to the carbon atom of the 5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl ring;
• wherein
• R6 is hydrogen, fluorine, methyl, ethyl, methoxy, ethoxy, trifluoromethoxy, hydroxyl, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino,
• wherein methyl and ethyl may be up to trisubstituted by fluorine;
• R7 is hydrogen, fluorine or methyl,
• wherein methyl may be up to trisubstituted by fluorine;
• or
• R6 and R7 together with the carbon atom to which they are bonded form a carbonyl group;
• or
• R6 and R7 together with the carbon atom to which they are bonded form a cyclopropyl or cyclobutyl ring;
• or
• R6 and R4 together with the carbon atoms to which they are bonded form a cyclopropyl or cyclobutyl ring;
• R8 is hydrogen, fluorine, methyl, ethyl, methoxy, ethoxy, trifluoromethoxy, hydroxyl, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino,
• wherein methyl and ethyl may be up to trisubstituted by fluorine;
• R9 is hydrogen, fluorine or methyl,
• wherein methyl may be up to trisubstituted by fluorine;
• or
• R8 and R9 together with the carbon atom to which they are bonded form a cyclopropyl or cyclobutyl ring;
• R1 is (C5-C6)-cycloalkyl, phenyl or 5- to 10-membered heteroaryl,
• wherein (C5-C6)-cycloalkyl may be substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, cyano, trifluoromethyl, methyl, ethyl, methoxy, and ethoxy,
• wherein methyl and ethyl may be up to trisubstituted by fluorine,
• wherein phenyl is substituted by 1 to 4 substituents independently selected from the group consisting of halogen, cyano, (C1-C4)-alkyl, (C3-C6)-cycloalkyl, trifluoromethyl, (C1-C4)-alkoxy, (C3-C5)-cycloalkoxy, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, hydroxycarbonyl, (C1-C4)-alkoxycarbonyl, aminocarbonyl, mono-(C1-C4)-alkylaminocarbonyl, di-(C1-C4)-alkylaminocarbonyl, (C1-C4)-alkylsulphanyl, (C1-C4)-alkylsulphonyl, (C1-C4)-alkylsulphonimidoyl, aminosulphonyl, mono-(C1-C4)-alkylaminosulphonyl, di-(C1-C4)-alkylaminosulphonyl, (C1-C4)-alkylsulphinyl, amino, mono-(C1-C4)-alkylamino, and di-(C1-C4)-alkylamino,
• or
• wherein phenyl may be fused to cyclopentyl, cyclohexyl, 5- to 6-membered heterocyclyl or 5- to 6-membered heteroaryl,
• wherein phenyl may be substituted by methyl, ethyl, chlorine, fluorine or methoxy,
• wherein cyclopentyl, cyclohexyl, 5- to 6-membered heterocyclyl and 5- to 6-membered heteroaryl may be substituted by 1 or 2 methyl or ethyl substituents,
• wherein methyl and ethyl may be substituted by methoxy, hydroxyl, monomethylamino or diethylamino and up to trisubstituted by fluorine,
• or
• wherein 5- to 10-membered heteroaryl may be substituted by 1 to 4 substituents independently selected from the group consisting of halogen, cyano, (C1-C4)-alkyl, (C3-C6)-cycloalkyl, trifluoromethyl, (C1-C4)-alkoxy, (C3-C5)-cycloalkoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, hydroxycarbonyl, (C1-C4)-alkoxycarbonyl, aminocarbonyl, mono-(C1-C4)-alkylaminocarbonyl, di-(C1-C4)-alkylaminocarbonyl, (C1-C4)-alkylsulphanyl, (C1-C4)-alkylsulphonyl, (C1-C4)-alkylsulphonimidoyl, aminosulphonyl, mono-(C1-C4)-alkylaminosulphonyl, di-(C1-C4)-alkylaminosulphonyl, (C1-C4)-alkylsulphinyl, amino, mono-(C1-C4)-alkylamino, and di-(C1-C4)-alkylamino,
• or
• wherein 5- to 10-membered heteroaryl may be fused to cyclopentyl, cyclohexyl or 5- to 6-membered heterocyclyl,
• wherein 5- to 10-membered heteroaryl may be substituted by methyl, ethyl, chlorine, fluorine or methoxy,
• wherein cyclopentyl, cyclohexyl and 5- to 6-membered heterocyclyl may be substituted by 1 or 2 (C1-C4)-alkyl substituents,
• wherein (C1-C4)-alkyl may be substituted by (C1-C4)-alkoxy, hydroxyl, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino and up to pentasubstituted by fluorine;
• R2 is a group of the formula
• wherein
• #3 marks the bond to the carbonyl carbon atom,
• r is 0 or 1,
• Z is S, SO, SO2, or CR14AR14B,
• wherein
• R14A is hydrogen, halogen, cyano, (C1-C4)-alkyl, cyclopropyl, trifluoromethyl, difluoromethyl, fluoromethyl, hydroxyl, methoxy, ethoxy, cyclopropoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, hydroxycarbonyl, aminocarbonyl, or amino,
• wherein (C1-C4)-alkyl may be substituted by hydroxyl, amino, mono-(C1-C4)-alkylamino, or di-(C1-C4)-alkylamino,
• R14B is hydrogen, fluorine, methyl or trifluoromethyl,
• or
• R14A and R14B together with the carbon atom to which they are bonded form a carbonyl group,
• R12 is hydrogen, cyano, methyl, ethyl, acetyl, or formyl,
• in which methyl may be substituted by hydroxyl or up to pentasubstituted by fluorine,
• in which acetyl is substituted by hydroxyl or up to trisubstituted by fluorine,
• R13 is hydrogen, fluorine or methyl,
• or
• R12 and R13 together with the carbon atoms to which they are bonded form a cyclopropyl ring,
• wherein the cyclopropyl ring may be up to disubstituted by fluorine,
• or
• R13 and R14A together with the carbon atoms to which they are bonded form a cyclopropyl or cyclobutyl ring,
• wherein the cyclopropyl or cyclobutyl ring may be up to disubstituted by fluorine,
• or
• R14A and R14B together with the carbon atom to which they are bonded form a cyclopropyl or cyclobutyl ring,
• wherein the cyclopropyl or cyclobutyl ring may be up to disubstituted by fluorine,
• wherein R13, R14A and R14B are hydrogen when R12 is not hydrogen,
• wherein R12 is hydrogen when one of the R13, R14A and R14B substituents is not hydrogen;
• or
• R2 is a group of the formula
• wherein
• #4 marks the bond to the carbonyl carbon atom,
• Y is NR5, CR16AR16B, oxygen, or sulphur,
• wherein
• R15 is hydrogen or methyl,
• R16A is hydrogen or methyl,
• R16B is hydrogen or methyl;
• R3 is hydrogen or methyl;
• R4 is hydrogen, fluorine, methyl, ethyl, methoxy, ethoxy, trifluoromethoxy, hydroxyl, mono-(C1-C4)-alkylamino, or di-(C1-C4)-alkylamino,
• wherein methyl and ethyl may be up to trisubstituted by fluorine;
• R5 is hydrogen, fluorine or methyl,
• wherein methyl may be up to trisubstituted by fluorine;
• or
• R4 and R5 together with the carbon atom to which they are bonded form a cyclopropyl ring,
• or a salt, a solvate, or a solvate of a salt thereof.

3:

• The compound according to claim 1, wherein:
• A is —CH2—, —CH(CH3)—, —CH2CH2—, #5—CH2CH(CH3)—***, #5—CH2C(CH3)2—***, #5—CH2CHF—***, or #5—CH2CF2—***,
• wherein #5 marks the bond to the nitrogen atom of the 5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl ring,
• wherein *** marks the bond to the R1 group;
• X is -#2—CR6R7—CR8R9—**,
• wherein #2 marks the bond to the carbon atom of the CR4R5— group,
• wherein ** marks the bond to the carbon atom of the 5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl ring;
• wherein
• R6 is hydrogen, fluorine, methyl, trifluoromethyl, or hydroxyl;
• R7 is hydrogen, fluorine, or methyl;
• or
• R6 and R7 together with the carbon atom to which they are bonded form a cyclopropyl ring;
• R1 is phenyl or 5- to 6-membered heteroaryl,
• wherein phenyl is substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy, trifluoromethoxy, hydroxycarbonyl, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, methylsulphanyl, methylsulphonyl, methylsulphonimidoyl, aminosulphonyl, and methylsulphinyl,
• or
• wherein phenyl may be fused to cyclopentyl, cyclohexyl, 5- to 6-membered heterocyclyl or 5- to 6-membered heteroaryl,
• wherein cyclopentyl, cyclohexyl, (C5-C6)-heterocyclyl and 5- to 6-membered heteroaryl may be substituted by 1 or 2 methyl or ethyl substituents,
• or
• wherein 5- to 6-membered heteroaryl may be substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, methylaminocarbonyl, tert-butylaminocarbonyl, and dimethylaminocarbonyl,
• wherein 5- to 6-membered heteroaryl may be fused to cyclopentyl, cyclohexyl, 5- to 6-membered heterocyclyl, phenyl or 5- to 6-membered heteroaryl,
• wherein 5- to 6-membered heteroaryl may be substituted by methyl, ethyl, chlorine, fluorine or methoxy,
• wherein cyclopentyl, cyclohexyl, 5- to 6-membered heterocyclyl, phenyl and 5- to 6-membered heteroaryl may be substituted by 1 or 2 (C1-C4)-alkyl substituents;
• R2 is a group of the formula
• wherein
• #3 marks the bond to the carbonyl carbon atom,
• r is 0 or 1,
• Z is S or CR14AR14B when r is 0,
• Z is S, SO, SO2 or CR14AR14B when r is 1,
• in each of which
• R14A is hydrogen, fluorine, methyl, trifluoromethyl, difluoromethyl, fluoromethyl, hydroxyl, methoxy, difluoromethoxyz or trifluoromethoxy,
• R14B is hydrogen or fluorine,
• or
• R14A and R14B together with the carbon atom to which they are bonded form a carbonyl group,
• R12 is hydrogen, cyano, methyl, acetyl, or formyl,
• wherein acetyl is substituted by hydroxyl or up to trisubstituted by fluorine,
• R13 is hydrogen, fluorine, or methyl,
• or
• R12 and R13 together with the carbon atoms to which they are bonded form a cyclopropyl ring,
• R13 and R14A together with the carbon atom to which they are bonded form a cyclopropyl ring,
• wherein the cyclopropyl ring may be up to disubstituted by fluorine,
• or
• R14A and R14B together with the carbon atom to which they are bonded form a cyclopropyl ring,
• wherein the cyclopropyl ring may be up to disubstituted by fluorine, wherein R13, R14A and R14B are hydrogen when R12 is not hydrogen, wherein R12 is hydrogen when one of the R13, R14A and R14B substituents is not hydrogen;
• R3 is hydrogen;
• R4 is hydrogen, fluorine, or methyl;
• and
• R5 is hydrogen,
• or a salt, a solvate, or a solvate of a salt thereof.

4:

• The compound according to claim 1, wherein:
• A is —CH2—, —CH(CH3)—, —CH2CH2—, #5—CH2CH(CH3)—***, #5—CH2C(CH3)2—***, #5—CH2CHF—***, or #5—CH2CF2—***,
• wherein #5 marks the bond to the nitrogen atom of the 5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl ring,
• wherein *** marks the bond to the R1 group;
• X is -#2—CR6R7—CR8R9—**,
• wherein #2 marks the bond to the carbon atom of the CR4R5— group,
• wherein ** marks the bond to the carbon atom of the 5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl ring;
• wherein
• R6 is hydrogen, fluorine, methyl, trifluoromethyl, or hydroxyl;
• R7 is hydrogen, fluorine, or methyl;
• or
• R6 and R7 together with the carbon atom to which they are bonded form a cyclopropyl ring;
• R8 is hydrogen, fluorine, methyl, or trifluoromethyl;
• R9 is hydrogen, fluorine, or methyl;
• R1 is phenyl or 5- to 6-membered heteroaryl,
• wherein phenyl is substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy, trifluoromethoxy, hydroxycarbonyl, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, methylsulphanyl, methylsulphonyl, methylsulphonimidoyl, aminosulphonyl, and methylsulphinyl,
• or
• wherein phenyl may be fused to cyclopentyl, cyclohexyl, 5- to 6-membered heterocyclyl or 5- to 6-membered heteroaryl,
• wherein cyclopentyl, cyclohexyl, 5- to 6-membered heterocyclyl and 5- to 6-membered heteroaryl may be substituted by 1 or 2 methyl or ethyl substituents,
• or
• wherein 5- to 6-membered heteroaryl may be substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, methylaminocarbonyl, tert-butylaminocarbonyl, and dimethylaminocarbonyl,
• wherein 5- to 6-membered heteroaryl may be fused to cyclopentyl, cyclohexyl, 5- to 6-membered heterocyclyl, phenyl or 5- to 6-membered heteroaryl,
• wherein 5- to 6-membered heteroaryl may be substituted by methyl, ethyl, chlorine, fluorine or methoxy,
• wherein cyclopentyl, cyclohexyl, 5- to 6-membered heterocyclyl, phenyl and 5- to 6-membered heteroaryl may be substituted by 1 or 2 (C1-C4)-alkyl substituents;
• R2 is a group of the formula
• wherein
• #3 marks the bond to the carbonyl carbon atom,
• r is 0 or 1,
• Z is S or CR14AR14B when r is 0, or
• Z is S, SO, SO2 or CR14AR14B when r is 1,
• in each of which
• R14A is hydrogen, fluorine, methyl, trifluoromethyl, difluoromethyl, fluoromethyl, hydroxyl, methoxy, difluoromethoxy or trifluoromethoxy,
• R14B is hydrogen or fluorine,
• or
• R14A and R14B together with the carbon atom to which they are bonded form a carbonyl group,
• R12 is hydrogen, cyano, methyl, acetyl or formyl,
• wherein acetyl is substituted by hydroxyl or up to trisubstituted by fluorine,
• R13 is hydrogen, fluorine or methyl,
• or
• R12 and R13 together with the carbon atoms to which they are bonded form a cyclopropyl ring,
• or
• R13 and R14A together with the carbon atom to which they are bonded form a cyclopropyl ring,
• wherein the cyclopropyl ring may be up to disubstituted by fluorine,
• or
• R14A and R14B together with the carbon atom to which they are bonded form a cyclopropyl ring,
• wherein the cyclopropyl ring may be up to disubstituted by fluorine, wherein R13, R14A and R14B are hydrogen when R12 is not hydrogen, wherein R12 is hydrogen when one of the R13, R14A and R14B substituents is not hydrogen;
• R3 is hydrogen;
• R4 is hydrogen, fluorine, or methyl;
• and
• R5 is hydrogen,
• or a salt, a solvate, or a solvate of a salt thereof.

5:

• The compound according to claim 1, wherein:
• A is —CH2—, —CH(CH3)—, —CH2CH2—, #5—CH2CH(CH3)—***, #5—CH2C(CH3)2—***, #5—CH2CHF—*** or #5—CH2CF2—***,
• wherein #5 marks the bond to the nitrogen atom of the 5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl ring,
• wherein *** marks the bond to the R1 group;
• X is -#2—CR6R7—CR8R9—**,
• wherein #2 marks the bond to the carbon atom of the CR4R5— group,
• wherein ** marks the bond to the carbon atom of the 5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl ring;
• wherein
• R6 is hydrogen, fluorine, methyl, trifluoromethyl, or hydroxyl;
• R7 is hydrogen, fluorine, or methyl;
• or
• R6 and R7 together with the carbon atom to which they are bonded form a cyclopropyl ring;
• R8 is hydrogen, fluorine, methyl or trifluoromethyl;
• R9 is hydrogen, fluorine or methyl;
• R1 is phenyl, pyrazolyl, imidazolyl, thiazolyl, thiophenyl, oxazolyl, oxadiazolyl, or pyridyl,
• wherein phenyl is substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy, trifluoromethoxy, hydroxycarbonyl, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, methylsulphanyl, methylsulphonyl, methylsulphonimidoyl, aminosulphonyl, and methylsulphinyl,
• or
• wherein phenyl may be fused to cyclopentyl, cyclohexyl, pyrazolyl, or pyridyl,
• wherein cyclopentyl, cyclohexyl, pyrazolyl or pyridyl may be substituted by 1 or 2 methyl or ethyl substituents,
• or
• wherein pyrazolyl, imidazolyl, thiazolyl, thiophenyl, oxazolyl, oxadiazolyl or pyridyl may be substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, methylaminocarbonyl, tert-butylaminocarbonyl, and dimethylaminocarbonyl,
• wherein pyrazolyl, imidazolyl, thiazolyl, thiophenyl, oxazolyl, oxadiazolyl or pyridyl may be fused to cyclopentyl, cyclohexyl, phenyl or pyridyl,
• wherein pyridyl may be substituted by methyl, ethyl, chlorine, fluorine, or methoxy,
• wherein cyclopentyl, cyclohexyl, phenyl and pyridyl may be substituted by 1 or 2 (C1-C4)-alkyl substituents;
• wherein
• #3 marks the bond to the carbonyl carbon atom,
• r is 0 or 1,
• Z is S or CR14AR14B when r is 0,
• Z is S, SO, SO2 or CR14AR14B when r is 1,
• in each of which
• R14A is hydrogen, fluorine, methyl, trifluoromethyl, difluoromethyl, fluoromethyl, hydroxyl, methoxy, difluoromethoxy or trifluoromethoxy,
• R14B is hydrogen or fluorine,
• or
• R14A and R14B together with the carbon atom to which they are bonded form a carbonyl group,
• R12 is hydrogen, cyano, methyl, acetyl or formyl,
• wherein acetyl is substituted by hydroxyl or up to trisubstituted by fluorine,
• R13 is hydrogen, fluorine, or methyl,
• or
• R12 and R13 together with the carbon atoms to which they are bonded form a cyclopropyl ring,
• or
• R13 and R14A together with the carbon atom to which they are bonded form a cyclopropyl ring,
• wherein the cyclopropyl ring may be up to disubstituted by fluorine,
• or
• R14A and R14B together with the carbon atom to which they are bonded form a cyclopropyl ring,
• wherein the cyclopropyl ring may be up to disubstituted by fluorine, wherein R13, R14A and R14B are hydrogen when R12 is not hydrogen, wherein R12 is hydrogen when one of the R13, R14A and R14B substituents is not hydrogen;
• R3 is hydrogen;
• R4 is hydrogen, fluorine, or methyl;
• and
• R5 is hydrogen,
• or a salt, a solvate, or a solvate of a salt thereof.

6:

• A process for preparing a compound of formula (I) according to claim 1, comprising either
• [A] reacting a compound of formula (II)
• wherein R3, R4, R5 and X are as defined in claim 1,
• and
• T1 is (C1-C4)-alkyl or benzyl,
• in an inert solvent in the presence of a suitable base with a compound of formula (III)
• wherein
• A1 is —CH2—, —CH(CH3)—, —CH2CH2—, #5—CH2CH(CH3)—***, #5—CH2C(CH3)2—***, #5—CH2CHF—***, or #5—CH2CF2—***,
• wherein #5 marks the bond to the nitrogen atom of the 5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl ring,
• wherein *** marks the bond to the R1 group,
• R1 is as defined in claim 1,
• and
• X1 is a suitable leaving group
• to give a compound of formula (IV)
• wherein A1, R1, R3, R4, R5, X and T1 are as defined above;
• converting the compound of formula (IV) to a compound of formula (V) by removing the “T1” group in an inert solvent in the presence of a suitable base or acid
• wherein A1, R1, R3, R4, R5 and X are as defined above;
• reacting the compound of formula (V) in an inert solvent under amide coupling conditions with an amine of the formula (VI-A) or (VI-B)
• wherein Y, Z, r, R12 and R13 are as defined in claim 1;
• removing any protecting groups present to provide the compound of formula (I);
• and
• optionally further converting the compound of formula (I) with the appropriate (i) solvents and/or (ii) acids or bases to the solvate, the salt, or the solvate of the salt thereof;
• or
• [B] reacting a compound of formula (II)
• wherein R3, R4, R5 and X are as defined in claim 1,
• and
• T1 is (C1-C4)-alkyl or benzyl,
• in an inert solvent in the presence of a suitable base with an amine of formula (VI-A) or (VI-B)
• wherein Y, Z, r R12 and R13 are as defined in claim 1,
• to give a compound of the formula (XXIII-A) or (XXIII-B)
• wherein R3, R4, R5, R12, R13, X, Y, Z, and r are as defined above;
• reacting the compound of formula (XXIII-A) or the compound of formula (XXIII-B) in an inert solvent in the presence of a suitable base with a compound of the formula (III)
• wherein
• A1 is —CH2—, —CH(CH3)—, —CH2CH2—, #5—CH2CH(CH3)—***, #5—CH2C(CH3)2—***, #5—CH2CHF—***, or #5—CH2CF2—***,
• wherein #5 marks the bond to the nitrogen atom of the 5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl ring,
• wherein *** marks the bond to the R1 group,
• R1 is as defined in claim 1,
• and
• X1 is a suitable leaving group;
• removing any protecting groups present to provide the compound of formula (I);
• and optionally further converting the compound of formula (I) with the appropriate (i) solvents and/or (ii) acids or bases to the solvate, the salt, or the solvate of the salt thereof;
• or
• [C] converting a compound of formula (VII)
• wherein R3, R4, R5 and X are as defined in claim 1, and
• T1 is (C1-C4)-alkyl or benzyl,
• T2 is 4-methoxybenzyl, benzyl, allyl, β-(trimethylsilyl)ethoxymethyl (SEM), methoxymethyl (MOM), or benzyloxymethyl,
• by hydrolysis of the ester group in an inert solvent in the presence of a suitable base or acid to a compound of formula (VIII)
• wherein R3, R4, R5, T2 and X are as defined above;
• reacting the compound of formula (VIII) in an inert solvent under amide coupling conditions with an amine of formula (VI-A) or formula (VI-B)
• wherein Y, Z, r, R12 and R13 are as defined in claim 1,
• to give a compound of the formula (IX-A) or (IX-B)
• wherein R3, R4, R5, R12, R13, T2, X, Y, Z, and r are as defined above;
• removing the protecting group “T2” in an inert solvent in the presence of a suitable base or acid or optionally in the presence of a suitable palladium catalyst to provide a compound of formula (X-A) or (X-B)
• wherein R3, R4, R5, R12, R13, X, Y, Z, and r are as defined above;
• reacting the compound of formula (X-A) or (X-B) in an inert solvent in the presence of a suitable base with a compound of the formula (III)
• wherein
• A1 is —CH2—, —CH(CH3)—, —CH2CH2—, #5—CH2CH(CH3)—***, #5—CH2C(CH3)2—***, #5—CH2CHF—***, or #5—CH2CF2—***,
• wherein #5 marks the bond to the nitrogen atom of the 5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl ring,
• wherein *** marks the bond to the R1 group,
• R1 is as defined in claim 1,
• and
• X1 is a suitable leaving group;
• removing any protecting groups present to provide the compound of formula (I);
• and optionally further converting the compound of formula (I) with the appropriate (i) solvents and/or (ii) acids or bases to the solvate, the salt, or the solvate of the salt thereof.