A process for preparing Degarelix having the formula Ac-AA1-AA10-NH2 or a pharmaceutically acceptable salt or solvate thereof, wherein AA1 is D-2Nal, AA2 is D-4Cpa, AA3 is D-3Pal, AA4 is Ser, AA5 is 4Aph(L-Hor), AA6 is D-Aph(Cbm), AA7 is Leu, AA8 is Lys(iPr), AA9 is Pro and AA10 is D-Ala, comprising:
- treating a Degarelix precursor according to formula II ((P1)AA1-AA2-AA3-AA4(P4)-AA5-AA6(P6)-AA7-AA8(P8)-AA9-AA10-NH2), or a salt or solvate thereof, with a cleaving agent, wherein formula II is as follows:
- wherein
- P1 is an amino protecting group;
- P4 is hydrogen or a hydroxyl protecting group;
- P6 is hydrogen or an amino protecting group;
- P8 is an amino protecting group chosen from 9-fluorenylmethyloxycarbonyl (Fmoc), benzyloxycarbonyl (Cbz or Z), 2-bromo-benzyloxycarbonyl (2-Br—Z), 2-chlorobenzyloxycarbonyl (2-Cl—Z), p-chlorobenzyloxycarbonyl, p-6-nitrobenzyloxycarbonyl, p-bromobenzyloxycarbonyl, and p-methoxybenzyloxycarbonyl, o-chlorobenzyloxycarbonyl, 2,4-dichlorobenzyloxycarbonyl, 2,6-dichlorobenzyloxycarbonyl, t-amyloxycarbonyl, isopropyloxycarbonyl, 2-(p-biphenylyl)-isopropyloxycarbonyl, cyclopentyloxycarbonyl, adamantyloxycarbonyl, cyclohexyloxycarbonyl, allyloxycarbonyl (Alloc) acetyl (Ac), benzoyl (Bz), trifluoroacetyl (Tfa), toluenesulfonyl (Tos), benzyl (Bn), triphenylmethyl (Trt), o-nitrophenyl-sulfenyl (Nps), t-butyl-dimethylsilyloxycarbonyl, [2-(3,5-dimethoxyphenyl)-propyl-2-oxycarbonyl](Ddz), 2,2,2-trichloroethyloxycarbonyl (Troc), biphenylylisopropyloxycarbonyl (Bpoc), and o-nitrobenzyloxycarbonyl;
- and
- wherein the process is a liquid-phase process,
- or
- a process for preparing Degarelix having the formula Ac-AA1-AA10-NH2 or a pharmaceutically acceptable salt or solvate thereof, wherein AA1 is D-2Nal, AA2 is D-4Cpa, AA3 is D-3Pal, AA4 is Ser, AA5 is 4Aph(L-Hor), AA6 is D-Aph(Cbm), AA7 is Leu, AA8 is Lys(iPr), AA9 is Pro and AA10 is D-Ala, comprising:
- treating a Degarelix precursor according to formula II ((P1)AA1-AA2-AA3-AA4(P4)-AA5-AA6(P6)-AA7-AA8(P8)-AA9-AA10-NH2), or a salt or solvate thereof, with a cleaving agent, wherein formula II is as follows:
- wherein
- P1 is an amino protecting group;
- P4 is hydrogen or a hydroxyl protecting group;
- P6 is hydrogen or an amino protecting group chosen from C5-C6 alkyl, acetyl (Ac), trityl, benzyl, p-methoxybenzyl, p-nitrobenzyl, p-chlorobenzyl, o-chlorobenzyl, 2,6-dichlorobenzyl, tetrahydropyranyl, tri(C1-C6)alkylsilyl, 2-methoxyethoxymethyl (MEM), 4-dimethylcarbamoylbenzyl, 9-fluorenylmethyl ethers, and O-phenoxyacetyl ethers;
- P8 is an amino protecting group;
- and
- wherein the process is a liquid-phase process,
- or
- a process for preparing Degarelix having the formula Ac-AA1-AA10-NH2 or a pharmaceutically acceptable salt or solvate thereof, wherein AA1 is D-2Nal, AA2 is D-4Cpa, AA3 is D-3Pal, AA4 is Ser, AA5 is 4Aph(L-Hor), AA6 is D-Aph(Cbm), AA7 is Leu, AA8 is Lys(iPr), AA9 is Pro and AA10 is D-Ala, comprising:
- treating a Degarelix precursor according to formula II ((P1)AA1-AA2-AA3-AA4(P4)-AA5-AA6(P6)-AA7-AA8(P8)-AA9-AA10-NH2), or a salt or solvate thereof, with a cleaving agent, wherein formula II is as follows:
- wherein
- P1 is an amino protecting group;
- P4 is hydrogen or is a hydroxyl protecting group chosen from C5-C6 alkyl, acetyl (Ac), trityl, benzyl, p-methoxybenzyl, p-nitrobenzyl, p-chlorobenzyl, o-chlorobenzyl, 2,6-dichlorobenzyl, tetrahydropyranyl, tri(C1-C6)alkylsilyl, 2-methoxyethoxymethyl (MEM), 4-dimethylcarbamoylbenzyl, 9-fluorenylmethyl ethers, and O-phenoxyacetyl ethers;
- P6 is hydrogen or an amino protecting group;
- P8 is an amino protecting group;
- and
- wherein the process is a liquid-phase process,
- or
- a process for preparing Degarelix having the formula Ac-AA1-AA10-NH2 or a pharmaceutically acceptable salt or solvate thereof, wherein AA1 is D-2Nal, AA2 is D-4Cpa, AA3 is D-3Pal, AA4 is Ser, AA5 is 4Aph(L-Hor), AA6 is D-Aph(Cbm), AA7 is Leu, AA8 is Lys(iPr), AA9 is Pro and AA10 is D-Ala, comprising:
- treating a Degarelix precursor according to formula II ((P1)AA1-AA2-AA3-AA4(P4)-AA5-AA6(P6)-AA7-AA8(P8)-AA9-AA10-NH2), or a salt or solvate thereof, with a cleaving agent, wherein formula II is as follows:
- wherein
- P1 is an amino protecting group;
- P4 is hydrogen or is a hydroxyl protecting group chosen from C5-C6 alkyl, acetyl (Ac), trityl, benzyl, p-methoxybenzyl, p-nitrobenzyl, p-chlorobenzyl, o-chlorobenzyl, 2,6-dichlorobenzyl, tetrahydropyranyl, tri(C1-C6)alkylsilyl, 2-methoxyethoxymethyl (MEM), 4-dimethylcarbamoylbenzyl, 9-fluorenylmethyl ethers, and O-phenoxyacetyl ethers;
- P6 is hydrogen or an amino protecting group chosen from C5-C6 alkyl, acetyl (Ac), trityl, benzyl, p-methoxybenzyl, p-nitrobenzyl, p-chlorobenzyl, o-chlorobenzyl, 2,6-dichlorobenzyl, tetrahydropyranyl, tri(C1-C6)alkylsilyl, 2-methoxyethoxymethyl (MEM), 4-dimethylcarbamoylbenzyl, 9-fluorenylmethyl ethers, and O-phenoxyacetyl ethers;
- P8 is an amino protecting group chosen from 9-fluorenylmethyloxycarbonyl (Fmoc), benzyloxycarbonyl (Cbz or Z), 2-bromo-benzyloxycarbonyl (2-Br—Z), 2-chlorobenzyloxycarbonyl (2-Cl—Z), p-chlorobenzyloxycarbonyl, p-6-nitrobenzyloxycarbonyl, p-bromobenzyloxycarbonyl, and p-methoxybenzyloxycarbonyl, o-chlorobenzyloxycarbonyl, 2,4-dichlorobenzyloxycarbonyl, 2,6-dichlorobenzyloxycarbonyl, t-amyloxycarbonyl, isopropyloxycarbonyl, 2-(p-biphenylyl)-isopropyloxycarbonyl, cyclopentyloxycarbonyl, adamantyloxycarbonyl, cyclohexyloxycarbonyl, allyloxycarbonyl (Alloc) acetyl (Ac), benzoyl (Bz), trifluoroacetyl (Tfa), toluenesulfonyl (Tos), benzyl (Bn), triphenylmethyl (Trt), o-nitrophenyl-sulfenyl (Nps), t-butyl-dimethylsilyloxycarbonyl, [2-(3,5-dimethoxyphenyl)-propyl-2-oxycarbonyl] (Ddz), 2,2,2-trichloroethyloxycarbonyl (Troc), biphenylylisopropyloxycarbonyl (Bpoc), and o-nitrobenzyloxycarbonyl;
- and
- wherein the process is a liquid-phase process.