Diastereomeric aminoalcohol and aminoether salts of 2-[(4r,s)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl]acetic acid and their use for enantiomeric separation

Abstract

The present invention relates to diastereomeric aminoalcohol or aminoether salts of 2-[(4R,S)- 8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]- 3,4-dihydroquinazolin-4-yl]acetic acid, a method of producing those and a method for enantiomeric separation. The invention further relates to methods of preparation of 2-[(4S)-8- fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl]acetic acid or salts or solvates thereof via enantiomeric separation from a mixture comprising 2-[(4R)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy- 5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl]acetic acid and 2-[(4S)-8-fluoro-2-[4- (3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl]acetic acid or salts or solvates thereof.

Description

[0001] Diastereomeric aminoalcohol and aminoether salts of 2-[(4R^S)-8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl] acetic acid and their use for enantiomeric separation

[0002] The present invention relates to aminoalcohol and aminoether salts of 2-[(4R,S)-8-fluoro- 2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl]acetic acid, a method of producing those and a method for enantiomeric separation. The invention further relates to methods of preparation of 2- [(4S)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5- (trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl]acetic acid (“Letermovir”) or salts or solvates thereof via enantiomeric separation from a mixture comprising 2-[(4R)-8- fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5- (trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl]acetic acid (“R-Enantiomer”) and Letermovir or salts or solvates or solvates of salts or co-crystals or solvates of co-crystals or salts of co-crystals or solvates of salts of co-crystals thereof.

[0003] Background of the invention

[0004] Cytomegalovirus (CMV) is a common opportunistic infection that causes significant morbidity and preventable mortality after solid-organ and allogeneic hematopoietic stem cell transplantation.

[0005] Human Cytomegalovirus is a species of virus that belongs to the viral family known as Herpesviridae or herpes viruses. It is typically abbreviated as HCMV and is alternatively known as human herpesvirus-5 (HHV-5). Within Herpesviridae, HCMV belongs to the Betaherpesvirinae subfamily, which also includes cytomegaloviruses from other mammals.

[0006] Letermovir is known as a highly active drug for addressing HCMV infection and extensively described in Lischka et al., In Vitro and In Vivo Activities of the Novel Anticytomegalovirus Compound Letermovir. Antimicrob. Agents Chemother. 2010, 54: p.1290-1297, and Kaul et al., First report of successful treatment of multidrug-resistant cytomegalovirus disease with the novel anti-CMV compound Letermovir. Am. J. Transplant. 2011, 11:1079-1084,' as well as Marschall et al, In Vitro Evaluation of the Activities of the Novel Anticytomegalovirus Compound Letermovir against Herpesviruses and Other Human Pathogenic Viruses. Antimicrob. Agents Chemother. 2012, 56: 1135- 1137.

[0007] The precise chemical name of Letermovir is 2-[(4S)-8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl]acetic acid, which has the structure as depicted below:

[0008] Letermovir was developed by the applicant as an antiviral agent, in particular for prophylaxis of the human cytomegalovirus (HCMV) in human transplant patients. The synthesis of Letermovir is disclosed in WO 2006 / 133822 and WO 2004 / 096778.

[0009] Salts of Letermovir are described in WO 2013 / 127971. Particularly, some solvates of sodium and calcium salts of Letermovir have been prepared in crystalline and amorphous form. In case of the sodium salt of Letermovir, mixed alcohol water solvates, such as methanol or ethanol hydrates were obtained (example 1 of WO 2013 / 127971). The trihydrate of sodium salt of Letermovir is described in WO 2021 / 170874 and the monohydrate form is disclosed in WO 2021 / 170879. A potassium salt of Letermovir and its solvates are described in WO 2021 / 170882. The tosylate and besylate salts of Letermovir and their preparation is disclosed in WO 2013 / 127968.

[0010] For preparation of enantiomerically pure Letermovir there is an inevitable need to separate enantiomers in one of the synthesis steps. In WO 2004 / 096778 the enantiomers are separated by preparative HPLC on a chiral column. In WO 2006 / 133822 enantiomeric separation of one of the synthesis intermediates via crystallization with (2S,3S)-2,3- bis[(4-methylbenzoyl)oxy]succinic acid is described. There remains a need, however, for a robust method of enantiomeric separation of the synthesis end-product 2-[(4R,S)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2- methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl]acetic acid, regardless of its synthesis method. It has been surprisingly discovered that the 4R- and 4S- enanti omers of 2-[(4R,S)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2- methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl]acetic acid can be efficiently separated via formation of the diastereomeric salts of aminoalcohols and aminoethers with very high enantiomeric purity. A particular advantage is that the synthesis end-product can be directly converted to Letermovir or the desired salt or solvate form thereof. A further advantage is that the method of the present invention is easily scalable for real manufacturing.

[0011] Description of the invention

[0012] The first aspect of the present invention relates to a method for producing 2-{(4S)8-fluoro- 2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetic acid (“Letermovir”) or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof, comprising the steps: i) providing a mixture comprising Letermovir and 2-{(4R)8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetic acid (“R-Enantiomer”) or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof; ii) contacting said mixture with an enantiomerically enriched compound of Formula (I) wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxy phenyl, benzyl and CH2OH,

[0013] R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4 -nitrophenyl, quinolinyl and methoxyquinolinyl,

[0014] R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3-C5-cycloalkyl,

[0015] R7 is H or C1-C6-alkyl, whereinR1 and R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, whereinR1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R1 and R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3-C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6- alkenyl, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring, thereby producing a Letermovir salt of the compound of Formula (I) and an R-Enantiomer salt of the compound of Formula (I), iii-1) separating the Letermovir salt of the compound of Formula (I); iv-1) converting the Letermovir salt of the compound of Formula (I) into Letermovir or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co- crystal thereof; and optionally v-1) isolating Letermovir or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof.

[0016] Another aspect of the present invention relates to a method for producing a Letermovir salt of a compound of Formula (I), comprising the steps: i) providing a mixture comprising Letermovir and R-Enantiomer or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co- crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof; ii) contacting said mixture with an enantiomerically enriched compound of Formula (I) wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxy phenyl, benzyl and CH2OH,

[0017] R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4 -nitrophenyl, quinolinyl and methoxyquinolinyl,

[0018] R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3-C5-cycloalkyl,

[0019] R7 is H or C1-C6-alkyl, whereinR1 and R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, whereinR1 and R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3-C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6- alkenyl, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring, thereby producing a Letermovir salt of the compound of Formula (I) and an R-Enantiomer salt of the compound of Formula (I); iii-1) separating the Letermovir salt of the compound of Formula (I).

[0020] Another aspect of the present invention relates to a method for producing an R- Enantiomer salt of a compound of Formula (I), comprising the steps: i) providing a mixture comprising Letermovir and R-Enantiomer or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co- crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof; ii) contacting said mixture with an enantiomerically enriched compound of Formula (I) wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxy phenyl, benzyl and CH2OH,

[0021] R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4 -nitrophenyl, quinolinyl and methoxyquinolinyl,

[0022] R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3-C5-cycloalkyl,

[0023] R7 is H or C1-C6-alkyl, whereinR1 and R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, whereinR1 and R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3-C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6- alkenyl, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring, thereby producing a Letermovir salt of the compound of Formula (I) and an R-Enantiomer salt of the compound of Formula (I); iii-2) separating the R-Enantiomer salt of the compound of Formula (I).

[0024] Another aspect of the present invention relates to a method for enantiomeric separation of a mixture comprising Letermovir and R-Enantiomer comprising the steps: i) providing a mixture comprising Letermovir and R-Enantiomer or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co- crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof; ii) contacting said mixture with an enantiomerically enriched compound of Formula (I) wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxy phenyl, benzyl and CH2OH,

[0025] R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4 -nitrophenyl, quinolinyl and methoxyquinolinyl,

[0026] R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3-C5-cycloalkyl,

[0027] R7 is H or C1-C6-alkyl, wherein R1 and R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R1 and R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring, thereby producing a Letermovir salt of the compound of Formula (I) and an R-Enantiomer salt of the compound of Formula (I), iii-1) separating the Letermovir salt of the compound of Formula (I); iv-1) transferring the Letermovir salt of the compound of Formula (I) into the compound of Formula (I) and Letermovir and optionally v-1) isolating Letermovir.

[0028] Another aspect of the present invention relates to a method for enantiomeric separation of a mixture comprising Letermovir and R-Enantiomer comprising the steps: i) providing a mixture comprising Letermovir and R-Enantiomer or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co- crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof; ii) contacting said mixture with an enantiomerically enriched compound of Formula (I) wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxy phenyl, benzyl and CH2OH,

[0029] R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4 -nitrophenyl, quinolinyl and methoxyquinolinyl,

[0030] R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3-C5-cycloalkyl,

[0031] R7 is H or C1-C6-alkyl, wherein R1 and R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R1 and R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3-C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6- alkenyl, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring, thereby producing a Letermovir salt of the compound of Formula (I) and an R-Enantiomer salt of the compound of Formula (I); iii-2) separating the R-Enantiomer salt of the compound of Formula (I); iv-2) transferring the R-Enantiomer salt of the compound of Formula (I) into the compound of Formula (I) and R-Enantiomer; and optionally v-2) isolating R-Enantiomer.

[0032] Another aspect of the present invention relates to use of a compound of Formula (I) for producing Letermovir or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof, wherein the compound of Formula (I) is wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxy phenyl, benzyl and CH2OH,

[0033] R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4 -nitrophenyl, quinolinyl and methoxyquinolinyl,

[0034] R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3-C5-cycloalkyl,

[0035] R7 is H or C1-C6-alkyl, wherein R1 and R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R1 and R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3-C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6- alkenyl, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring, in particular by the method as described in the present invention.

[0036] Another aspect of the present invention relates to use of a compound of Formula (I) for producing R-Enantiomer or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof, wherein the compound of Formula (I) is wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxy phenyl, benzyl and CH2OH, R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4 -nitrophenyl, quinolinyl and methoxyquinolinyl,

[0037] R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3-C5-cycloalkyl,

[0038] R7 is H or C1-C6-alkyl, wherein R1 and R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R1 and R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3-C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6- alkenyl, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring, in particular by the method as described in the present invention.

[0039] Another aspect of the present invention relates to use of a compound of Formula (I) for enantiomeric separation of a mixture comprising Letermovir and R-Enantiomer, or salts thereof or solvates thereof or solvates of salts thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof, wherein the compound of Formula (I) is wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxy phenyl, benzyl and CH2OH,

[0040] R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4 -nitrophenyl, quinolinyl and methoxyquinolinyl,

[0041] R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3-C5-cycloalkyl,

[0042] R7 is H or C1-C6-alkyl, wherein R1 and R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R1 and R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3-C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6- alkenyl, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring, in particular by the method as described in the present invention.

[0043] Another aspect of the present invention relates to aminoalcohol and aminoether salts of Letermovir and R-Enantiomer, in particular those specifically described in the present invention.

[0044] It has been surprisingly discovered that the 4R- and 4S-enantiomers of 2-[(4R,S)-8- fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5- (trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl]acetic acid can be efficiently separated via formation of the diastereomeric salts of enantiomerically enriched aminoalcohols and aminoethers. In particular, diastereomeric aminoalcohol / aminoether salts of enantiomeric pairs have different solubilities, which can be used for efficient separation via selective crystallization so that one diastereomeric salt precipitates out of the solution, whereas the second diastereomeric salt remains in a solution or vice versa. The selectivity can be controlled by the stereoisomeric configuration of the chiral agent. This stereoisomeric configuration has a good match with the Cahn-Ingold-Prelog nomenclature. For example, the S / S and R / R enantiomeric pairs of Letermovir and the R- Enantiomer with 1,2-aminoalcohols are commonly significantly less soluble than their respective diastereomers (R / S and S / R). It has been surprisingly discovered that the enantiomeric purity of the obtained diastereomeric salts, which can be easily converted to respectively Letermovir, R-Enantiomer or salts or solvates or co-crystals thereof, is very high and enantiomeric excess of more than 95% can be achieved.

[0045] Detailed description

[0046] It is noted that the term “comprising” also encompasses the meaning “consisting of’, e.g., a group of members comprising said members also encompasses a group of members consisting only of these members. As used herein, the terms “Letermovir” or “4S-Enantiomer” refer to 2-[(4S)-8-fluoro-2- [4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl]acetic acid.

[0047] As used herein, the terms “R-Enantiomer” or “4R-Enantiomer” refer to 2-[(4R)-8-fluoro- 2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl]acetic acid.

[0048] As used herein, the term “Letermovir salt of the compound of Formula (I)” refers to an electrically neutral chemical compound, consisting of positively charged cations and negatively charged anions. In one example, Letermovir salt of the compound of Formula (I) consists of positively charged Letermovir cations and negatively charged anions of the compound of Formula (I). In another example, Letermovir salt of the compound of Formula (I) consists of negatively charged Letermovir anions and positively charged cations of the compound of Formula (I).

[0049] As used herein, the term “R-Enantiomer salt of the compound of Formula (I)” refers to an electrically neutral chemical compound, consisting of positively charged cations and negatively charged anions. In one example, R-Enantiomer salt of the compound of Formula (I) consists of positively charged R-Enantiomer cations and negatively charged anions of the compound of Formula (I). In another example, R-Enantiomer salt of the compound of Formula (I) consists of negatively charged R-Enantiomer anions and positively charged cations of the compound of Formula (I).

[0050] As used herein, the terms “S / S”, “R / R”, “S / R” and “R / S” with respect to enantiomeric pairs of Letermovir and the R-Enantiomer with chiral 1,2-aminoalcohols or 1,2- aminoethers refer to diastereomeric salts, in which the first letter indicates the stereometric configuration of Letermovir or the R-Enantiomer and second letter indicates the stereometric configuration of chiral 1,2-aminoalcohols or 1,2-aminoethers. For example, “S / S” salt refers to Letermovir salt with an S chiral 1,2-aminoalcohol or 1,2- aminoether. “R / R” salt refers to R-Enantiomer salt with an S chiral 1,2-aminoalcohol or 1,2-aminoether. “S / R” salt refers to Letermovir salt with an R chiral 1,2-aminoalcohol or 1,2-aminoether. “R / S” salt refers to R-Enantiomer salt with an S chiral 1,2-aminoalcohol or 1,2-aminoether. As used herein, the term “transferring” with respect to the Letermovir salt of the compound of Formula (I) or the R-Enantiomer salt of the compound of Formula (I) refers to the process of converting said salt consisting of positively charged cations and negatively charged anions into the neutral compound of Formula (I) and the neutral Letermovir or the neutral R-Enantiomer, respectively.

[0051] As used herein, the term “enantiomerically pure” or “enantiomerically enriched” means a composition that comprises one stereoisomer of a compound, in particular an aminoalcohol or an aminoether, and is substantially free of other stereoisomers of that compound. In certain embodiments as used herein, a composition with an enantiomeric excess (“ee”) of at least 80%, preferably at least 85%, more preferably at least 90%, even more preferably at least 95%, most preferred at least 99% is enantiomerically enriched.

[0052] The term "room temperature" as used herein, is synonymous to the term "standard room temperature" and refers to a temperature in the range of from 19°C to 26°C.

[0053] For example, "cooled down to room temperature" means "cooled down to a temperature in the range of from 19°C to 26°C".

[0054] As used herein, the term “crystal” refers to any three-dimensional ordered array of molecules that diffracts X-rays.

[0055] The term "polymorph" refers to a particular crystal form (i.e. structure of crystal lattice) of a compound, in particular Letermovir or a salt, or a solvate, or a solvate of a salt thereof that can exist in more than one crystal form in the solid state.

[0056] As used herein, the term “solvates” refers to those forms of a compound, in particular, Letermovir or R-Enantiomer, which form a complex through coordination with solvent molecules. Hydrates are a special form of solvates in which the coordination takes place with water. The term “solvates” includes also solvates of salts, unless otherwise specified.

[0057] As used herein, the term “salt” refers to derivatives of the disclosed compounds wherein the parent compound, in particular Letermovir, is modified by converting an existing acid or base moiety to its salt form. Examples of salts include but are not limited to mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. Particular examples include sodium, potassium, calcium, besylate and tosylate salts as well as the salts of aminoalcohols and aminoethers described herein. The salts of the present invention can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods, in particular those as described in WO 2013 / 127971, WO 2013 / 127968, WO 2021 / 170874, WO 2021 / 170879 or WO 2021 / 170882.

[0058] As used herein, the term "co-crystal" refers to crystalline materials composed of two or more different molecular and / or ionic compounds in the same crystal lattice excluding solvents so that at least two of them are associated by non-ionic and noncovalent bonds.

[0059] Within the scope of the present invention the terms “obtained by” and “obtainable by” have the same meaning and are used interchangeably.

[0060] As used herein the term "solvent” refers to a liquid or a mixture of liquids which is suitable for dissolving or solvating a component or material described herein. According to the methods of the present invention, a solvent is selected from the group consisting of ketones, such as acetone, methyl ethyl ketone, cyclohexanone, 4-methylcyclohexanone, 4-methyl-2-pentanone or 3 -pentanone; alkanes, such as pentane, hexane, heptane or isooctane; cycloalkanes, such as cyclohexane or cyclopentane; aromatic solvents, such as chlorobenzene, 1,2-dichlorobenzene, cumene, toluene or xylenes; esters such as ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, ethyl propionate, methyl propionate, isoamyl propionate, isobutyl propionate, hexyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, cyclohexyl butyrate, benzyl butyrate, isobutyl formate, ethyl formate, ethyl formate, isopropyl formate, butyl formate, pentyl formate, diethylene glycol monoethyl ether acetate and ethylene glycol diacetate; ethers, such as diisopropyl ether, cyclopentyl methyl ether, butyl ether, diethoxymethane, anisole, ethylene glycol dimethyl ether, diethylene glycol diethyl ether or dimethoxyethane; alcohols such as ethanol, methanol, 2-butanol, isopropanol, n-butanol, diethylene glycol, isobutanol, isopentanol or tert- butanol; nitriles, such as acetonitrile; carbonates, such as dimethyl carbonate or diethyl carbonate; and water, or mixtures thereof. According to the methods of the present invention, preferably the solvent is selected from the group consisting of acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, isoamyl propionate, isobutyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, isoamyl butyrate, diethylene glycol monoethyl ether acetate, ethylene glycol diacetate, cyclohexyl butyrate, benzyl butyrate, diisopropylether, cyclopentyl methyl ether, cumene, isopropanol, 2-butanol, acetonitrile and dimethylcarbonate or mixtures thereof. According to the methods of the present invention, more preferably the solvent is selected from the group consisting of acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, isoamyl propionate, isobutyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, isoamyl butyrate, diethylene glycol monoethyl ether acetate, ethylene glycol diacetate, cyclohexyl butyrate, benzyl butyrate, or mixtures thereof. According to the methods of the present invention, most preferred the solvent is pentyl acetate, ethyl butyrate, propyl butyrate or mixtures thereof.

[0061] As used herein the term “antisolvent” refers to a liquid, which reduces the solubility of Letermovir in a solvent. In one embodiment, the solvent is selected from the group consisting of acetic acid, formic acid, triethylamine, ethyl acetate, butyl acetate, methyl acetate, isobutyl acetate, propyl acetate, isopropyl acetate, ethyl formate, isopropanol, 1- propanol, n-pentanol, ethanol, methanol, n-butanol, 2-butanol, 2-methyl-lpropanol, 3- m ethyl- 1 -butanol, tert-butanol, cyclohexanone, acetone, methyl ethyl ketone, 3- pentanone, methyl butyl ketone, methyl isobutyl ketone, tetrahydrofuran, 1,2- dimethoxyethane, dioxane, 2-ethoxyethanol, 2-methoxyethanol, ethyleneglycol, formamide, N,N-dimethylacetamide, N,N-dimethylformamide, dimethylsulfoxide, nitromethane, pyridine, sulfolane, tetralin, 1,2-di chloroethane, di chloromethane, 1,1,2- tri chloroethane, 1,1,1 -tri chloroethane, chloroform, chlorobenzene, toluene, cumene, xylenes, anisole, acetonitrile, N-methyl pyrrolidone, dimethyl carbonate, pentyl acetate, or mixtures thereof, and the antisolvent is selected from the group consisting of n-heptane, pentane, n-octane, diisopropyl ether, cyclohexane, hexane, methylcyclohexane, tert-butyl methyl ether, methyl tert-butyl ether ethyl ether, cyclopentyl methyl ether, and water, or mixtures thereof. In one embodiment, the solvent is selected from the group consisting of acetone, acetonitrile, ethyl acetate, isobutyl acetate, isopropyl acetate, propyl acetate, butyl acetate, dimethyl carbonate, chlorobenzene, chloroform, 1,2-di chloroethane, dichloromethane, dioxane, ethanol, ethyl formate, isobutanol, isopropanol, methyl acetate, methyl ethyl ketone, methyl isobutyl ketone, methanol, nitromethane, 3- pentanone, 1 -propanol, tert-butanol, 1,1,1 -tri chloroethane, tetrahydrofuran, toluene, 3- m ethyl- 1 -butanol, N,N-dimethylformamide, and xylenes, or mixtures thereof, and the antisolvent is selected from the group consisting of cyclohexane, diisopropyl ether, tert- butyl methyl ether, ethyl ether, water and n-heptane, or mixtures thereof. In one embodiment, the solvent is selected from the group consisting of acetone, acetonitrile, ethyl acetate, isobutyl acetate, isopropyl acetate, propyl acetate, butyl acetate, dimethyl carbonate, chlorobenzene, chloroform, 1,2-di chloroethane, di chloromethane, dioxane, ethanol, ethyl formate, isobutanol, isopropanol, methyl acetate, methyl ethyl ketone, methyl isobutyl ketone, methanol, nitromethane, 3 -pentanone, 1 -propanol, tert-butanol, 1,1,1 -tri chloroethane, tetrahydrofuran, toluene, and xylenes, or mixtures thereof, and the antisolvent is selected from the group consisting of cyclohexane, diisopropyl ether, water and n-heptane, or mixtures thereof. In a preferred embodiment the solvent is selected from the group consisting of acetone, acetonitrile, ethyl acetate, ethanol, isopropanol, methanol, methyl ethyl ketone, tetrahydrofuran, dioxane, toluene, 3 -methyl- 1 -butanol, tert-butanol, N,N-dimethylformamide and dichloromethane or mixtures thereof, and the antisolvent is selected from the group consisting of n-heptane, diisopropyl ether, tert- butyl methyl ether, ethyl ether and water, or mixtures thereof. In a more preferred embodiment, the solvent is acetone or acetonitrile and the antisolvent is water.

[0062] As used herein, the term “seeding” refers to a procedure in which a small quantity of crystals (known as seeds) is added in order to promote and control crystallization in a given supersaturated solution. In the particular case of the enantiomeric resolution of the racemate, the added crystals are those of the less soluble diastereomeric salt of the chiral agent and Letermovir (or R-Enantiomer).

[0063] As used herein the term "contacting” with respect to two materials refers to the addition of the first material to the second material or the addition of the second material to the first material. In particular, the term “contacting” refers to the addition of a solid to a solvent or the addition of a solvent to a solid.

[0064] As used herein, the term “racemic” or “racemate” means about 50%±5% of one enantiomer and about 50%±5% of the other enantiomer relative to all chiral centers in the molecule. As used herein the term "alkyl" by itself or as part of another substituent refers to a radical of alkane having the number of carbon atoms designated (i.e. C1-C6-alkyl means one to six carbon atoms, C1-C5-alkyl means one to five carbon atoms, C1-C4-alkyl means one to four carbon atoms, C1-C3-alkyl means one to three carbon atoms) and includes straight and branched chains. Non-limiting examples include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, neopentyl, and hexyl. For the avoidance of doubt where two alkyl moieties are present in a group, the alkyl moieties may be the same or different.

[0065] As used herein the term "alkenyl" by itself or as part of another substituent refers to an alkyl group containing one or more carbon-carbon double bonds, wherein the position of the double bond may vary along the carbon chain. Examples of alkenyl groups include ethylenyl (-CH=CH2) and propenyl (-CH2-CH=CH2).

[0066] As used herein the term "cycloalkyl" refers to a monocyclic nonaromatic group wherein each of the atoms forming the ring (i.e. skeletal atoms) is a carbon atom. In one embodiment, the cycloalkyl group is saturated or partially unsaturated. In one embodiment, cycloalkyl groups include groups having 3 to 5 ring atoms (C3-C5- cycloalkyl), such as cyclopropyl, cyclobutyl or cyclopentyl.

[0067] As used herein, the term “oxocyclic ring” refers to a monocyclic nonaromatic group, wherein one of the atoms forming the ring is oxygen and each of the remaining atoms forming the ring is a carbon atom. In one embodiment the oxocyclic ring has 3 to 7 ring carbon atoms (C3-C7-oxocyclic ring), preferably 3 to 6 carbon atoms (G-Ce-oxocyclic ring). Illustrative examples include, but are not limited to tetrahydrofuran, tetrahydropyran and oxepane.

[0068] As used herein, the term “methoxyphenyl” refers to a phenyl group, which is substituted with one or more, in particular, one, two or three methoxy groups, e.g. -Ph -OCH3. Similarly, the term “methoxyquinolinyl” refers to a quinolinyl group, which is substituted with one or more, in particular, one, two or three methoxy groups.

[0069] As used herein, the term “quinolinyl” refers to a radical derived from quinoline, i.e. an aromatic heterocycle, characterized by a double-ring structure composed of a benzene and a pyridine ring fused at two adjacent carbon atoms. As used herein, the term “quinine” refers to (R)-[(2S,4S,5R)-5-ethenyl-l- azabicyclo[2.2.2]octan-2-yl](6-methoxyqinolin-4-yl)methanol.

[0070] As used herein, the term “quinidine” refers to (S)-[(2R,4S,5R)-5-ethenyl-l- azabicyclo[2.2.2]octan-2-yl](6-methoxyqinolin-4-yl)methanol.

[0071] As used herein, a wavy bond in a Markush formula denotes at least one chiral center, which is either in the R- or S-configuration. For example, the compound of Formula (I) encompasses the following structures (la)-(Id):

[0072] (la) (lb) (Ic) (Id).

[0073] Analogously, the compound of Formula (VI) encompasses the following structures (Via) and (VIb):

[0074] (Via) (VIb).

[0075] Analogously, the compound of Formula (VII) encompasses the following structures (Vila) and (Vllb):

[0076] (Vila) (Vllb).

[0077] If not specified otherwise, particular embodiments of the present invention refer to any method for producing Letermovir, any method for producing an aminoalcohol / aminoether salt of Letermovir, any method for producing an aminoalcohol / aminoether salt of R-Enantiomer or any method for enantiomeric separation disclosed herein.

[0078] The first aspect of the present invention relates to a method for producing 2-{(4S)8-fluoro- 2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetic acid (“Letermovir”) or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof, comprising the steps: i) providing a mixture comprising Letermovir and 2-{(4R)8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetic acid (“R-Enantiomer”) or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof; ii) contacting said mixture with an enantiomerically enriched compound of Formula (I) wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxy phenyl, benzyl and CH2OH,

[0079] R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4 -nitrophenyl, quinolinyl and methoxyquinolinyl,

[0080] R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3-C5-cycloalkyl,

[0081] R7 is H or C1-C6-alkyl, wherein R1 and R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R1 and R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3-C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6- alkenyl, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring, thereby producing a Letermovir salt of the compound of Formula (I) and an R-Enantiomer salt of the compound of Formula (I), iii-1) separating the Letermovir salt of the compound of Formula (I); iv-1) converting the Letermovir salt of the compound of Formula (I) into Letermovir or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co- crystal thereof; and optionally v-1) isolating Letermovir or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof.

[0082] In one embodiment, the present invention relates to a method for producing 2-{(4S)8- fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-

[0083] (trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetic acid (“Letermovir”) or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof, comprising the steps: i) providing a mixture comprising Letermovir and 2-{(4R)8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetic acid (“R-Enantiomer”) or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof; ii) contacting said mixture with an enantiomerically enriched compound of Formula (I) wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxyphenyl, benzyl and CH2OH,

[0084] R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4 -nitrophenyl, quinolinyl and methoxyquinolinyl,

[0085] R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3-C5-cycloalkyl,

[0086] R7 is H or C1-C6-alkyl, wherein R1 and R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R1 and R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring, thereby producing a Letermovir salt of the compound of Formula (I) and an R-Enantiomer salt of the compound of Formula (I), iii-1) separating the Letermovir salt of the compound of Formula (I); iv-1) converting the Letermovir salt of the compound of Formula (I) into Letermovir or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co- crystal thereof; and optionally v-1) isolating Letermovir or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof.

[0087] In one embodiment of said method for producing Letermovir said Letermovir is in an amorphous state and said method further comprises precipitation of Letermovir obtained in step iv-1) or v-1) from a solvent selected from the group consisting of acetic acid, formic acid, triethylamine, ethyl acetate, butyl acetate, methyl acetate, isobutyl acetate, propyl acetate, isopropyl acetate, ethyl formate, isopropanol, 1 -propanol, n-pentanol, ethanol, methanol, n-butanol, 2-butanol, 2-methyl-l propanol, 3 -methyl- 1 -butanol, tert- butanol, cyclohexanone, acetone, methyl ethyl ketone, 3 -pentanone, methyl butyl ketone, methyl isobutyl ketone, tetrahydrofuran, 1,2-dimethoxy ethane, dioxane, 2-ethoxy ethanol, 2-methoxyethanol, ethyleneglycol, formamide, N,N-dimethylacetamide, N,N- dimethylformamide, dimethylsulfoxide, nitromethane, pyridine, sulfolane, tetralin, 1,2- di chloroethane, di chloromethane, 1,1,2-tri chloroethane, 1,1,1 -tri chloroethane, chloroform, chlorobenzene, toluene, cumene, xylenes, anisole, acetonitrile, N-methyl pyrrolidone, dimethyl carbonate, pentyl acetate, or mixtures thereof, by an antisolvent selected from the group consisting of n-heptane, pentane, n-octane, diisopropyl ether, cyclohexane, hexane, methylcyclohexane, tert-butyl methyl ether, ethyl ether, cyclopentyl methyl ether, and water, or mixtures thereof, preferably from a solvent selected from the group consisting of acetone, acetonitrile, ethyl acetate, isobutyl acetate, isopropyl acetate, propyl acetate, butyl acetate, dimethylcarbonate, chlorobenzene, chloroform, 1,2-di chloroethane, dichloromethane, dioxane, ethanol, ethyl formate, isobutanol, isopropanol, methyl acetate, methyl ethyl ketone, methyl isobutyl ketone, methanol, nitromethane, 3 -pentanone, 1 -propanol, tert-butanol, 1,1,1 -tri chloroethane, tetrahydrofuran, toluene, 3 -methyl- 1 -butanol, N,N-dimethylformamide and xylenes, or mixtures thereof, by an antisolvent selected from the group consisting of cyclohexane, diisopropyl ether, water, tert-butyl methyl ether, ethyl ether, and n-heptane, or mixtures thereof, more preferably from a solvent is selected from the group consisting of acetone, acetonitrile, ethyl acetate, isobutyl acetate, isopropyl acetate, propyl acetate, butyl acetate, dimethyl carbonate, chlorobenzene, chloroform, 1,2-di chloroethane, dichloromethane, dioxane, ethanol, ethyl formate, isobutanol, isopropanol, methyl acetate, methyl ethyl ketone, methyl isobutyl ketone, methanol, nitromethane, 3-pentanone, 1-propanol, tert- butanol, 1,1,1 -tri chloroethane, tetrahydrofuran, toluene, and xylenes, or mixtures thereof, and the antisolvent is selected from the group consisting of cyclohexane, diisopropyl ether, water and n-heptane, or mixtures thereof, even more preferably from a solvent selected from the group consisting of acetone, acetonitrile, ethyl acetate, ethanol, isopropanol, methanol, methyl ethyl ketone, tetrahydrofuran, dioxane, toluene, 3-methyl- 1 -butanol, tert-butanol, N,N-dimethylformamide and di chloromethane or mixtures thereof, by an antisolvent selected from the group consisting of n-heptane, diisopropyl ether, tert-butyl methyl ether, ethyl ether and water, or mixtures thereof, most preferred from a water miscible solvent acetone or acetonitrile into excess stirred water, to obtain amorphous Letermovir, followed by isolation via filtration or centrifugation, e.g. by the method as described in Example 3b in WO 2014 / 202737 and in Example 6A in WO 2013 / 127971.

[0088] Another aspect of the present invention relates to a method for producing a Letermovir salt of a compound of Formula (I), comprising the steps: i) providing a mixture comprising Letermovir and R-Enantiomer or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co- crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof; ii) contacting said mixture with an enantiomerically enriched compound of Formula (I) wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxy phenyl, benzyl and CH2OH,

[0089] R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4 -nitrophenyl, quinolinyl and methoxyquinolinyl,

[0090] R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3-C5-cycloalkyl,

[0091] R7 is H or C1-C6-alkyl, wherein R1 and R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R1 and R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3-C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6- alkenyl, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring , thereby producing a Letermovir salt of the compound of Formula (I) and an R-Enantiomer salt of the compound of Formula (I); iii-1) separating the Letermovir salt of the compound of Formula (I).

[0092] In one embodiment the present invention relates to a method for producing a Letermovir salt of a compound of Formula (I), comprising the steps: i) providing a mixture comprising Letermovir and R-Enantiomer or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co- crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof; ii) contacting said mixture with an enantiomerically enriched compound of Formula (I) wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxy phenyl, benzyl and CH2OH,

[0093] R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4 -nitrophenyl, quinolinyl and methoxyquinolinyl,

[0094] R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3-C5-cycloalkyl,

[0095] R7 is H or C1-C6-alkyl, wherein R1 and R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R1 and R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring , thereby producing a Letermovir salt of the compound of Formula (I) and an R-Enantiomer salt of the compound of Formula (I); iii-1) separating the Letermovir salt of the compound of Formula (I).

[0096] In one embodiment, said Letermovir salt of a compound of Formula (I) in step iii-1) is isolated in a form of a precipitate, in particular by filtration or centrifugation.

[0097] In one embodiment, said Letermovir salt of a compound of Formula (I) in step iii-1) is isolated in a form of a mother liquor, in particular by filtration or centrifugation, optionally followed by evaporation of the mother liquor.

[0098] Another aspect of the present invention relates to a method for producing an R- Enantiomer salt of a compound of Formula (I), comprising the steps: i) providing a mixture comprising Letermovir and R-Enantiomer or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co- crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof; ii) contacting said mixture with an enantiomerically enriched compound of Formula (I) wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxy phenyl, benzyl and CH2OH,

[0099] R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4 -nitrophenyl, quinolinyl and methoxyquinolinyl,

[0100] R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3-C5-cycloalkyl,

[0101] R7 is H or C1-C6-alkyl, wherein R1 and R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R1 and R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3-C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6- alkenyl, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring, thereby producing a Letermovir salt of the compound of Formula (I) and an R-Enantiomer salt of the compound of Formula (I); iii-2) separating the R-Enantiomer salt of the compound of Formula (I).

[0102] In one embodiment, said R-Enantiomer salt of a compound of Formula (I) in step iii-2) is isolated in a form of a precipitate, in particular by filtration or centrifugation.

[0103] In one embodiment, said R-Enantiomer salt of a compound of Formula (I) in step iii-2) is isolated in a form of a mother liquor, in particular by filtration or centrifugation, optionally followed by evaporation of the mother liquor.

[0104] Another aspect of the present invention relates to a method for enantiomeric separation of a mixture comprising Letermovir and R-Enantiomer comprising the steps: i) providing a mixture comprising Letermovir and R-Enantiomer or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co- crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof; ii) contacting said mixture with an enantiomerically enriched compound of Formula (I) wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxy phenyl, benzyl and CH2OH, R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4 -nitrophenyl, quinolinyl and methoxyquinolinyl,

[0105] R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3-C5-cycloalkyl,

[0106] R7 is H or C1-C6-alkyl, wherein R1 and R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R1 and R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3-C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6- alkenyl, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring, thereby producing a Letermovir salt of the compound of Formula (I) and an R-Enantiomer salt of the compound of Formula (I), iii-1) separating the Letermovir salt of the compound of Formula (I); iv-1) transferring the Letermovir salt of the compound of Formula (I) into the compound of Formula (I) and Letermovir and optionally v-1) isolating Letermovir. In one embodiment, said Letermovir in step v-1) is isolated in a form of a precipitate, in particular by filtration or centrifugation.

[0107] In one embodiment, said Letermovir in step v-1) is isolated in a form of a mother liquor, in particular by filtration or centrifugation, optionally followed by evaporation of the mother liquor.

[0108] In one embodiment, said method for enantiomeric separation further comprises precipitation of Letermovir obtained in step iv-1) or v-1) from a solvent selected from the group consisting of acetic acid, formic acid, triethylamine, ethyl acetate, butyl acetate, methyl acetate, isobutyl acetate, propyl acetate, isopropyl acetate, ethyl formate, isopropanol, 1 -propanol, n-pentanol, ethanol, methanol, n-butanol, 2-butanol, 2-methyl- 1 propanol, 3 -methyl- 1 -butanol, tert-butanol, cyclohexanone, acetone, methyl ethyl ketone, 3-pentanone, methyl butyl ketone, methyl isobutyl ketone, tetrahydrofuran, 1,2- dimethoxyethane, dioxane, 2-ethoxyethanol, 2-methoxyethanol, ethyleneglycol, formamide, N,N-dimethylacetamide, N,N-dimethylformamide, dimethylsulfoxide, nitromethane, pyridine, sulfolane, tetralin, 1,2-di chloroethane, di chloromethane, 1,1,2- tri chloroethane, 1,1,1 -tri chloroethane, chloroform, chlorobenzene, toluene, cumene, xylenes, anisole, acetonitrile, N-methyl pyrrolidone, dimethyl carbonate, pentyl acetate, or mixtures thereof, by an antisolvent selected from the group consisting of n-heptane, pentane, n-octane, diisopropyl ether, cyclohexane, hexane, methylcyclohexane, tert-butyl methyl ether, ethyl ether, cyclopentyl methyl ether, and water, or mixtures thereof, preferably from a solvent selected from the group consisting of acetone, acetonitrile, ethyl acetate, isobutyl acetate, isopropyl acetate, propyl acetate, butyl acetate, dimethylcarbonate, chlorobenzene, chloroform, 1,2-di chloroethane, di chloromethane, dioxane, ethanol, ethyl formate, isobutanol, isopropanol, methyl acetate, methyl ethyl ketone, methyl isobutyl ketone, methanol, nitromethane, 3-pentanone, 1-propanol, tert- butanol, 1,1,1 -tri chloroethane, tetrahydrofuran, toluene, 3 -methyl- 1 -butanol, N,N- dimethylformamide and xylenes, or mixtures thereof, by an antisolvent selected from the group consisting of cyclohexane, diisopropyl ether, tert-butyl methyl ether, ethyl ether water and n-heptane, or mixtures thereof, more preferably from a solvent selected from the group consisting of acetone, acetonitrile, ethyl acetate, isobutyl acetate, isopropyl acetate, propyl acetate, butyl acetate, dimethyl carbonate, chlorobenzene, chloroform, 1,2-dichloroethane, di chloromethane, dioxane, ethanol, ethyl formate, isobutanol, isopropanol, methyl acetate, methyl ethyl ketone, methyl isobutyl ketone, methanol, nitromethane, 3 -pentanone, 1 -propanol, tert-butanol, 1,1,1 -tri chloroethane, tetrahydrofuran, toluene, and xylenes, or mixtures thereof, and the antisolvent is selected from the group consisting of cyclohexane, diisopropyl ether, water and n-heptane, or mixtures thereof, even more preferably from a solvent selected from the group consisting of acetone, acetonitrile, ethyl acetate, ethanol, isopropanol, methanol, methyl ethyl ketone, tetrahydrofuran, dioxane, toluene, 3 -methyl- 1 -butanol, tert-butanol, N,N- dimethylformamide and dichloromethane or mixtures thereof, by an antisolvent selected from the group consisting of n-heptane, diisopropyl ether, tert-butyl methyl ether, ethyl ether and water, or mixtures thereof, most preferred from a water miscible solvent acetone or acetonitrile into excess stirred water, to obtain amorphous Letermovir, followed by isolation via filtration or centrifugation.

[0109] In one embodiment, said method for enantiomeric separation of a mixture comprising Letermovir and R-Enantiomer further comprises the steps: vi-1) isolating the R-Enantiomer salt of the compound of Formula (I); vii-1) transferring the R-Enantiomer salt of the compound of Formula (I) into the compound of Formula (I) and R-Enantiomer; and optionally viii-1) isolating R-Enantiomer.

[0110] In one embodiment, said R-Enantiomer in step viii-1) is isolated in a form of a precipitate, in particular by filtration or centrifugation.

[0111] In one embodiment, said R-Enantiomer in step viii-1) is isolated in a form of a mother liquor, in particular by filtration or centrifugation, optionally followed by evaporation of the mother liquor.

[0112] Another aspect of the present invention relates to a method for enantiomeric separation of a mixture comprising Letermovir and R-Enantiomer comprising the steps: i) providing a mixture comprising Letermovir and R-Enantiomer or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co- crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof; ii) contacting said mixture with an enantiomerically enriched compound of Formula (I) wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxy phenyl, benzyl and CH2OH,

[0113] R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4 -nitrophenyl, quinolinyl and methoxyquinolinyl,

[0114] R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3-C5-cycloalkyl,

[0115] R7 is H or C1-C6-alkyl, wherein R1 and R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R1 and R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3-C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6- alkenyl, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring, thereby producing a Letermovir salt of the compound of Formula (I) and an R-Enantiomer salt of the compound of Formula (I); iii-2) separating the R-Enantiomer salt of the compound of Formula (I); iv-2) transferring the R-Enantiomer salt of the compound of Formula (I) into the compound of Formula (I) and R-Enantiomer; and optionally v-2) isolating R-Enantiomer.

[0116] In one embodiment, the present invention relates to a method for enantiomeric separation of a mixture comprising Letermovir and R-Enantiomer comprising the steps: i) providing a mixture comprising Letermovir and R-Enantiomer or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co- crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof; ii) contacting said mixture with an enantiomerically enriched compound of Formula (I) wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxy phenyl, benzyl and CH2OH, R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4 -nitrophenyl, quinolinyl and methoxyquinolinyl,

[0117] R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3-C5-cycloalkyl,

[0118] R7 is H or C1-C6-alkyl, wherein R1 and R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R1 and Rs, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring, wherein Rs and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring, thereby producing a Letermovir salt of the compound of Formula (I) and an R-Enantiomer salt of the compound of Formula (I); iii-2) separating the R-Enantiomer salt of the compound of Formula (I); iv-2) transferring the R-Enantiomer salt of the compound of Formula (I) into the compound of Formula (I) and R-Enantiomer; and optionally v-2) isolating R-Enantiomer. In one embodiment, said R-Enantiomer in step v-2) is isolated in a form of a precipitate, in particular by filtration or centrifugation.

[0119] In one embodiment, said R-Enantiomer in step v-2) is isolated in a form of a mother liquor, in particular by filtration or centrifugation, optionally followed by evaporation of the mother liquor.

[0120] In one embodiment, said method for enantiomeric separation of a mixture comprising Letermovir and R-Enantiomer further comprises the steps: vi-2) isolating the Letermovir salt of the compound of Formula (I); vii-2) transferring the Letermovir salt of the compound of Formula (I) into the compound of Formula (I) and Letermovir; and optionally viii-2) isolating Letermovir.

[0121] In one embodiment, said Letermovir in step viii-2) is isolated in a form of a precipitate, in particular by filtration or centrifugation.

[0122] In one embodiment, said Letermovir in step viii-2) is isolated in a form of a mother liquor, in particular by filtration or centrifugation, optionally followed by evaporation of the mother liquor.

[0123] In one embodiment, said method for enantiomeric separation further comprises precipitation of Letermovir obtained in step vii-2) or viii-2) from a solvent selected from the group consisting of acetic acid, formic acid, triethylamine, ethyl acetate, butyl acetate, methyl acetate, isobutyl acetate, propyl acetate, isopropyl acetate, ethyl formate, isopropanol, 1 -propanol, n-pentanol, ethanol, methanol, n-butanol, 2-butanol, 2-methyl- 1 -propanol, 3 -methyl- 1 -butanol, tert-butanol, cyclohexanone, acetone, methyl ethyl ketone, 3-pentanone, methyl butyl ketone, methyl isobutyl ketone, tetrahydrofuran, 1,2- dimethoxyethane, dioxane, 2-ethoxyethanol, 2-methoxyethanol, ethyleneglycol, formamide, N,N-dimethylacetamide, N,N-dimethylformamide, dimethyl sulfoxide, nitromethane, pyridine, sulfolane, tetralin, 1,2-di chloroethane, di chloromethane, 1,1,2- tri chloroethane, 1,1,1 -tri chloroethane, chloroform, chlorobenzene, toluene, cumene, xylenes, anisole, acetonitrile, N-methyl pyrrolidone, dimethyl carbonate, pentyl acetate, or mixtures thereof, by an antisolvent selected from the group consisting of n-heptane, pentane, n-octane, diisopropyl ether, cyclohexane, hexane, methylcyclohexane, tert-butyl methyl ether, ethyl ether, cyclopentyl methyl ether, and water, or mixtures thereof, preferably from a solvent selected from the group consisting of acetone, acetonitrile, ethyl acetate, isobutyl acetate, isopropyl acetate, propyl acetate, butyl acetate, dimethylcarbonate, chlorobenzene, chloroform, 1,2-di chloroethane, di chloromethane, dioxane, ethanol, ethyl formate, isobutanol, isopropanol, methyl acetate, methyl ethyl ketone, methyl isobutyl ketone, methanol, nitromethane, 3-pentanone, 1-propanol, tert- butanol, 1,1,1 -tri chloroethane, tetrahydrofuran, toluene, 3 -methyl- 1 -butanol, N,N- dimethylformamide and xylenes, or mixtures thereof, by an antisolvent selected from the group consisting of cyclohexane, diisopropyl ether, tert-butyl methyl ether, ethyl ether, water and n-heptane, or mixtures thereof, more preferably from a solvent selected from the group consisting of acetone, acetonitrile, ethyl acetate, isobutyl acetate, isopropyl acetate, propyl acetate, butyl acetate, dimethyl carbonate, chlorobenzene, chloroform, 1,2-dichloroethane, di chloromethane, dioxane, ethanol, ethyl formate, isobutanol, isopropanol, methyl acetate, methyl ethyl ketone, methyl isobutyl ketone, methanol, nitromethane, 3-pentanone, 1-propanol, tert-butanol, 1,1,1 -tri chloroethane, tetrahydrofuran, toluene, and xylenes, or mixtures thereof, and the antisolvent is selected from the group consisting of cyclohexane, diisopropyl ether, water and n-heptane, or mixtures thereof, even more preferably from a solvent selected from the group consisting of acetone, acetonitrile, ethyl acetate, ethanol, isopropanol, methanol, methyl ethyl ketone, tetrahydrofuran, dioxane, toluene, 3 -methyl- 1 -butanol, tert-butanol, N,N- dimethylformamide and dichloromethane or mixtures thereof, by an antisolvent selected from the group consisting of n-heptane, diisopropyl ether, tert-butyl methyl ether, ethyl ether and water, or mixtures thereof, most preferred from a water miscible solvent acetone or acetonitrile into excess stirred water, to obtain amorphous Letermovir, followed by isolation via filtration or centrifugation.

[0124] In one embodiment of said method for producing Letermovir or a salt thereof or a solvate thereof or a salt of solvate thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof, the method for producing a Letermovir salt or an R-Enantiomer salt of a compound of Formula (I) or said method for enantiomeric separation step (ii) is carried out in a solid state. In one embodiment step (ii) is carried without a solvent. In one embodiment step (ii) is conducted by means of mixing a mixture comprising Letermovir and R-Enantiomer or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof with the compound of formula (I) in a solid state and grinding in a ball mill.

[0125] In one embodiment, step ii) is carried out in a solid state and separating the Letermovir salt of the compound of Formula (I) in step iii-1) is conducted by means of dissolving the R-Enantiomer salt of the compound of Formula (I) in a solvent selected from the group consisting of ketones, such as acetone, methyl ethyl ketone, cyclohexanone, 4- m ethylcyclohexanone, 4-methyl-2-pentanone or 3 -pentanone; alkanes, such as pentane, hexane, heptane or isooctane; cycloalkanes, such as cyclohexane or cyclopentane; aromatic solvents, such as chlorobenzene, 1,2-di chlorobenzene, cumene, toluene or xylenes; esters such as ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, ethyl propionate, methyl propionate, isoamyl propionate, isobutyl propionate, hexyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, cyclohexyl butyrate, benzyl butyrate, isobutyl formate, ethyl formate, ethyl formate, isopropyl formate, butyl formate, pentyl formate, diethylene glycol monoethyl ether acetate and ethylene glycol diacetate; ethers, such as diisopropyl ether, cyclopentyl methyl ether, butyl ether, diethoxymethane, anisole, ethylene glycol dimethyl ether, diethylene glycol diethyl ether or dimethoxyethane; alcohols such as ethanol, methanol, 2-butanol, isopropanol, n-butanol, diethylene glycol, isobutanol, isopentanol or tert-butanol; nitriles, such as acetonitrile; and carbonates, such as dimethyl carbonate or diethyl carbonate; or mixtures thereof, preferably selected from the group consisting of acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, isoamyl propionate, isobutyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, isoamyl butyrate, diethylene glycol monoethyl ether acetate, ethylene glycol diacetate, cyclohexyl butyrate, benzyl butyrate, diisopropylether, cyclopentyl methyl ether, cumene, isopropanol, 2- butanol, acetonitrile and dimethylcarbonate or mixtures thereof, and isolating the solid phase comprising the Letermovir salt of the compound of Formula (I).

[0126] In one embodiment, step ii) is carried out in a solid state and separating the Letermovir salt of the compound of Formula (I) in step iii-1) is conducted by means of dissolving the R-Enantiomer salt of the compound of Formula (I) in a solvent selected from the group consisting of isopropanol, acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate isobutyl acetate and pentyl acetate, or mixtures thereof, preferably selected from the group consisting of ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate isobutyl acetate and pentyl acetate, or mixtures thereof, more preferably selected from the group consisting of pentyl acetate, ethyl butyrate, propyl butyrate or mixtures thereof, and isolating the solid phase comprising the Letermovir salt of the compound of Formula (I).

[0127] In one embodiment, step ii) is carried out in a solid state and separating the Letermovir salt of the compound of Formula (I) in step iii-1) is conducted by means of dissolving the R-Enantiomer salt of the compound of Formula (I) in a solvent selected from the group consisting of isopropanol, acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate isobutyl acetate and pentyl acetate, or mixtures thereof, preferably selected from the group consisting of ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate isobutyl acetate and pentyl acetate, or mixtures thereof, more preferably selected from the group consisting of pentyl acetate, ethyl butyrate, propyl butyrate or mixtures thereof, and isolating the solid phase comprising the Letermovir salt of the compound of Formula (I), wherein the compound of Formula (I) is a compound of Formula (II) or (III) wherein

[0128] R3 is selected from the group consisting of H, C1-C3-alkyl and phenyl,

[0129] R7 is H or C1-C3-alkyl, R8 is selected from the group consisting of H, OH, methyl or ethyl, wherein R7 and R8, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring.

[0130] In one embodiment, step ii) is carried out in a solid state and separating the Letermovir salt of the compound of Formula (I) in step iii-1) is conducted by means of dissolving the R-Enantiomer salt of the compound of Formula (I) in a solvent selected from the group consisting of isopropanol, acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate isobutyl acetate and pentyl acetate, or mixtures thereof, preferably selected from the group consisting of ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate isobutyl acetate and pentyl acetate, or mixtures thereof, more preferably selected from the group consisting of pentyl acetate, ethyl butyrate, propyl butyrate or mixtures thereof, and isolating the liquid phase comprising the R-Enantiomer salt of the compound of Formula (I), wherein the compound of Formula (I) is a compound of Formula (II) or (III) wherein

[0131] R3 is selected from the group consisting of H, C1-C3-alkyl and phenyl,

[0132] R7 is H or C1-C3-alkyl, R8 is selected from the group consisting of H, OH, methyl or ethyl, wherein R7 and R8, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring. In a preferred embodiment, the compound of Formula (II) is a compound of Formula (Ila) wherein

[0133] R3 is selected from the group consisting of H, C1-C3-alkyl, and phenyl,

[0134] R7 is H or C1-C3-alkyl, R8 is H or OH, wherein R7 and R8, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a tetrahydrofuran ring.

[0135] In another preferred embodiment, the compound of Formula (II) is a compound of Formula (lib) wherein R8 is H, methyl or ethyl.

[0136] In another preferred embodiment, the compound of Formula (III) is a compound of Formula (Illa) wherein R3 is H, CH2OH or methyl.

[0137] In one embodiment, step ii) is carried out in a solid state and separating the Letermovir salt of the compound of Formula (I) in step iii-1) is conducted by means of dissolving the Letermovir salt of the compound of Formula (I) in a solvent selected from the group consisting of isopropanol, acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate isobutyl acetate and pentyl acetate, or mixtures thereof, preferably selected from the group consisting of ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate isobutyl acetate and pentyl acetate, or mixtures thereof, more preferably selected from the group consisting of pentyl acetate, ethyl butyrate, propyl butyrate or mixtures thereof, and isolating the solid phase comprising the R-Enantiomer salt of the compound of Formula (I), wherein the compound of Formula (I) is a compound of Formula (IV) or (V)

[0138] (IV) (V) wherein

[0139] R3 is selected from the group consisting of H, C1-C3-alkyl and phenyl,

[0140] R7 is H or C1-C3-alkyl, R8 is selected from the group consisting of H, OH, methyl or ethyl, wherein R7 and R8, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring.

[0141] In one embodiment, step ii) is carried out in a solid state and separating the Letermovir salt of the compound of Formula (I) in step iii-1) is conducted by means of dissolving the Letermovir salt of the compound of Formula (I) in a solvent selected from the group consisting of isopropanol, acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate isobutyl acetate and pentyl acetate, or mixtures thereof, preferably selected from the group consisting of ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate isobutyl acetate and pentyl acetate, or mixtures thereof, more preferably selected from the group consisting of pentyl acetate, ethyl butyrate, propyl butyrate or mixtures thereof, and isolating the liquid phase comprising the Letermovir salt of the compound of Formula (I), wherein the compound of Formula (I) is a compound of Formula (IV) or (V)

[0142] (IV) (V) wherein

[0143] R3 is selected from the group consisting of H, C1-C3-alkyl and phenyl,

[0144] R7 is H or C1-C3-alkyl, R8 is selected from the group consisting of H, OH, methyl or ethyl, wherein R7 and R8, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring.

[0145] In a preferred embodiment, the compound of Formula (IV) is a compound of Formula (IVa) wherein

[0146] R3 is selected from the group consisting of H, C1-C3-alkyl, and phenyl,

[0147] R7 is H or C1-C3-alkyl, R8 is H or OH, wherein R7 and R8, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a tetrahydrofuran ring.

[0148] In another preferred embodiment, the compound of Formula (IV) is a compound of Formula (IVb) wherein R8 is H, methyl, or ethyl.

[0149] In another preferred embodiment, the compound of Formula (V) is a compound of Formula (Va) wherein R3 is H, CH2OH or methyl.

[0150] In one embodiment, step ii) is carried out in a solid state according to any of the preceding embodiments and said method further comprises precipitation of Letermovir obtained in step iv-1) or v-1) from a solvent selected from the group consisting of acetic acid, formic acid, triethylamine, ethyl acetate, butyl acetate, methyl acetate, isobutyl acetate, propyl acetate, isopropyl acetate, ethyl formate, isopropanol, 1 -propanol, n-pentanol, ethanol, methanol, n-butanol, 2-butanol, 2-methyl-l propanol, 3 -methyl- 1 -butanol, tert-butanol, cyclohexanone, acetone, methyl ethyl ketone, 3 -pentanone, methyl butyl ketone, methyl isobutyl ketone, tetrahydrofuran, 1,2-dimethoxy ethane, dioxane, 2-ethoxy ethanol, 2- methoxyethanol, ethyleneglycol, formamide, N,N-dimethylacetamide, N,N- dimethylformamide, dimethylsulfoxide, nitromethane, pyridine, sulfolane, tetralin, 1,2- di chloroethane, di chloromethane, 1,1,2-tri chloroethane, 1,1,1 -tri chloroethane, chloroform, chlorobenzene, toluene, cumene, xylenes, anisole, acetonitrile, N-methyl pyrrolidone, dimethyl carbonate, pentyl acetate, or mixtures thereof, by an antisolvent selected from the group consisting of n-heptane, pentane, n-octane, diisopropyl ether, cyclohexane, hexane, methylcyclohexane, tert-butyl methyl ether, ethyl ether, cyclopentyl methyl ether, and water, or mixtures thereof, preferably from a solvent selected from the group consisting of acetone, acetonitrile, ethyl acetate, isobutyl acetate, isopropyl acetate, propyl acetate, butyl acetate, dimethylcarbonate, chlorobenzene, chloroform, 1,2-di chloroethane, dichloromethane, dioxane, ethanol, ethyl formate, isobutanol, isopropanol, methyl acetate, methyl ethyl ketone, methyl isobutyl ketone, methanol, nitromethane, 3 -pentanone, 1 -propanol, tert-butanol, 1,1,1 -tri chloroethane, tetrahydrofuran, toluene, 3 -methyl- 1 -butanol, N,N-dimethylformamide and xylenes, or mixtures thereof, by an antisolvent selected from the group consisting of cyclohexane, diisopropyl ether, tert-butyl methyl ether, ethyl ether, water and n-heptane, or mixtures thereof, more preferably from a solvent selected from the group consisting of acetone, acetonitrile, ethyl acetate, isobutyl acetate, isopropyl acetate, propyl acetate, butyl acetate, dimethyl carbonate, chlorobenzene, chloroform, 1,2-di chloroethane, dichloromethane, dioxane, ethanol, ethyl formate, isobutanol, isopropanol, methyl acetate, methyl ethyl ketone, methyl isobutyl ketone, methanol, nitromethane, 3 -pentanone, 1 -propanol, tert- butanol, 1,1,1 -tri chloroethane, tetrahydrofuran, toluene, and xylenes, or mixtures thereof, and the antisolvent is selected from the group consisting of cyclohexane, diisopropyl ether, water and n-heptane, or mixtures thereof, even more preferably from a solvent selected from the group consisting of acetone, acetonitrile, ethyl acetate, ethanol, isopropanol, methanol, methyl ethyl ketone, tetrahydrofuran, dioxane, toluene, 3-methyl- 1 -butanol, tert-butanol, N,N-dimethylformamide and di chloromethane or mixtures thereof, by an antisolvent selected from the group consisting of n-heptane, diisopropyl ether, tert-butyl methyl ether, ethyl ether and water, or mixtures thereof, most preferred from a water miscible solvent acetone or acetonitrile into excess stirred water, to obtain amorphous Letermovir, followed by isolation via filtration or centrifugation.

[0151] In one embodiment of said method for producing Letermovir or a salt thereof or a solvate thereof or a salt of solvate thereof, the method for producing a Letermovir salt or an R- Enantiomer salt of a compound of Formula (I) or said method for enantiomeric separation step (ii) is carried out in a liquid phase. In one embodiment, step (ii) is carried out in presence of a solvent selected from the group consisting of ketones, such as acetone, methyl ethyl ketone, cyclohexanone, 4-methylcyclohexanone, 4-methyl-2-pentanone or 3-pentanone; alkanes, such as pentane, hexane, heptane or isooctane; cycloalkanes, such as cyclohexane or cyclopentane; aromatic solvents, such as chlorobenzene, 1,2- dichlorobenzene, cumene, toluene or xylenes; esters such as ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, ethyl propionate, methyl propionate, isoamyl propionate, isobutyl propionate, hexyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, cyclohexyl butyrate, benzyl butyrate, isobutyl formate, ethyl formate, ethyl formate, isopropyl formate, butyl formate, pentyl formate, diethylene glycol monoethyl ether acetate and ethylene glycol diacetate; ethers, such as diisopropyl ether, cyclopentyl methyl ether, butyl ether, di ethoxy methane, anisole, ethylene glycol dimethyl ether, diethylene glycol diethyl ether or dimethoxyethane; alcohols such as ethanol, methanol, 2-butanol, isopropanol, n- butanol, diethylene glycol, isobutanol, isopentanol or tert-butanol; nitriles, such as acetonitrile; and carbonates, such as dimethyl carbonate or diethyl carbonate; or mixtures thereof, preferably selected from the group consisting of acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, isoamyl propionate, isobutyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, isoamyl butyrate, di ethylene glycol monoethyl ether acetate, ethylene glycol diacetate, cyclohexyl butyrate, benzyl butyrate, diisopropylether, cyclopentyl methyl ether, cumene, isopropanol, 2-butanol, acetonitrile and dimethylcarbonate or mixtures thereof.

[0152] In one embodiment, the mixture comprising Letermovir or R-Enantiomer or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof is provided in a solid phase and the compound of Formula (I) is provided in a form of a solution in a solvent selected from the group consisting of ketones, such as acetone, methyl ethyl ketone, cyclohexanone, 4-methylcyclohexanone, 4-methyl-2- pentanone or 3-pentanone; alkanes, such as pentane, hexane, heptane or isooctane; cycloalkanes, such as cyclohexane or cyclopentane; aromatic solvents, such as chlorobenzene, 1,2-dichlorobenzene, cumene, toluene or xylenes; esters such as ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, ethyl propionate, methyl propionate, isoamyl propionate, isobutyl propionate, hexyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, cyclohexyl butyrate, benzyl butyrate, isobutyl formate, ethyl formate, ethyl formate, isopropyl formate, butyl formate, pentyl formate, diethylene glycol monoethyl ether acetate and ethylene glycol diacetate; ethers, such as diisopropyl ether, cyclopentyl methyl ether, butyl ether, diethoxymethane, anisole, ethylene glycol dimethyl ether, diethylene glycol diethyl ether or dimethoxyethane; alcohols such as ethanol, methanol, 2-butanol, isopropanol, n-butanol, diethylene glycol, isobutanol, isopentanol or tert- butanol; nitriles, such as acetonitrile; and carbonates, such as dimethyl carbonate or diethyl carbonate; or mixtures thereof, preferably selected from the group consisting of acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, isoamyl propionate, isobutyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, isoamyl butyrate, diethylene glycol monoethyl ether acetate, ethylene glycol diacetate, cyclohexyl butyrate, benzyl butyrate, diisopropylether, cyclopentyl methyl ether, cumene, isopropanol, 2-butanol, acetonitrile and dimethylcarbonate or mixtures thereof.

[0153] In one embodiment, the mixture comprising Letermovir or R-Enantiomer or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof is provided in a form of a solution in a solvent selected from the group consisting of ketones, such as acetone, methyl ethyl ketone, cyclohexanone, 4- methylcyclohexanone, 4-methyl-2-pentanone or 3 -pentanone; alkanes, such as pentane, hexane, heptane or isooctane; cycloalkanes, such as cyclohexane or cyclopentane; aromatic solvents, such as chlorobenzene, 1,2-di chlorobenzene, cumene, toluene or xylenes; esters such as ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, ethyl propionate, methyl propionate, isoamyl propionate, isobutyl propionate, hexyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, cyclohexyl butyrate, benzyl butyrate, isobutyl formate, ethyl formate, ethyl formate, isopropyl formate, butyl formate, pentyl formate, diethylene glycol monoethyl ether acetate and ethylene glycol diacetate; ethers, such as diisopropyl ether, cyclopentyl methyl ether, butyl ether, diethoxymethane, anisole, ethylene glycol dimethyl ether, diethylene glycol diethyl ether or dimethoxyethane; alcohols such as ethanol, methanol, 2-butanol, isopropanol, n-butanol, diethylene glycol, isobutanol, isopentanol or tert-butanol; nitriles, such as acetonitrile; and carbonates, such as dimethyl carbonate or diethyl carbonate; or mixtures thereof, preferably selected from the group consisting of acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, isoamyl propionate, isobutyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, isoamyl butyrate, diethylene glycol monoethyl ether acetate, ethylene glycol diacetate, cyclohexyl butyrate, benzyl butyrate, diisopropylether, cyclopentyl methyl ether, cumene, isopropanol, 2- butanol, acetonitrile and dimethylcarbonate or mixtures thereof, and the compound of Formula (I) is provided in a solid state.

[0154] In one embodiment, step ii) is carried out in a liquid state according to any of the preceding embodiments and said method further comprises precipitation of Letermovir obtained in step iv-1) or v-1) from a solvent selected from the group consisting of acetic acid, formic acid, triethylamine, ethyl acetate, butyl acetate, methyl acetate, isobutyl acetate, propyl acetate, isopropyl acetate, ethyl formate, isopropanol, 1 -propanol, n- pentanol, ethanol, methanol, n-butanol, 2-butanol, 2-methyl-l propanol, 3 -methyl- 1- butanol, tert-butanol, cyclohexanone, acetone, methyl ethyl ketone, 3 -pentanone, methyl butyl ketone, methyl isobutyl ketone, tetrahydrofuran, 1,2-dimethoxy ethane, dioxane, 2- ethoxyethanol, 2-methoxyethanol, ethylene glycol, formamide, N,N-dimethylacetamide, N,N-dimethylformamide, dimethylsulfoxide, nitromethane, pyridine, sulfolane, tetralin, 1,2-dichloroethane, di chloromethane, 1,1,2-tri chloroethane, 1,1,1 -tri chloroethane, chloroform, chlorobenzene, toluene, cumene, xylenes, anisole, acetonitrile, N-methyl pyrrolidone, dimethyl carbonate, pentyl acetate, or mixtures thereof, by an antisolvent selected from the group consisting of n-heptane, pentane, n-octane, diisopropyl ether, cyclohexane, hexane, methylcyclohexane, tert-butyl methyl ether, ethyl ether, cyclopentyl methyl ether, and water, or mixtures thereof, preferably from a solvent selected from the group consisting of acetone, acetonitrile, ethyl acetate, isobutyl acetate, isopropyl acetate, propyl acetate, butyl acetate, dimethylcarbonate, chlorobenzene, chloroform, 1,2-dichloroethane, dichloromethane, dioxane, ethanol, ethyl formate, isobutanol, isopropanol, methyl acetate, methyl ethyl ketone, methyl isobutyl ketone, methanol, nitromethane, 3 -pentanone, 1 -propanol, tert-butanol, 1,1,1 -tri chloroethane, tetrahydrofuran, toluene, 3 -methyl- 1 -butanol, N,N-dimethylformamide and xylenes, or mixtures thereof, by an antisolvent selected from the group consisting of cyclohexane, diisopropyl ether, tert-butyl methyl ether, ethyl ether, water and n-heptane, or mixtures thereof, more preferably from a solvent selected from the group consisting of acetone, acetonitrile, ethyl acetate, isobutyl acetate, isopropyl acetate, propyl acetate, butyl acetate, dimethyl carbonate, chlorobenzene, chloroform, 1,2-dichloroethane, dichloromethane, dioxane, ethanol, ethyl formate, isobutanol, isopropanol, methyl acetate, methyl ethyl ketone, methyl isobutyl ketone, methanol, nitromethane, 3 -pentanone, 1 -propanol, tert- butanol, 1,1,1 -tri chloroethane, tetrahydrofuran, toluene, and xylenes, or mixtures thereof, and the antisolvent is selected from the group consisting of cyclohexane, diisopropyl ether, water and n-heptane, or mixtures thereof, even more preferably from a solvent selected from the group consisting of acetone, acetonitrile, ethyl acetate, ethanol, isopropanol, methanol, methyl ethyl ketone, tetrahydrofuran, dioxane, toluene, 3-methyl- 1 -butanol, tert-butanol, N,N-dimethylformamide and di chloromethane or mixtures thereof, by an antisolvent selected from the group consisting of n-heptane, diisopropyl ether, tert-butyl methyl ether, ethyl ether and water, or mixtures thereof, most preferred from a water miscible solvent acetone or acetonitrile into excess stirred water, to obtain amorphous Letermovir, followed by isolation via filtration or centrifugation.

[0155] A mixture comprising Letermovir and R-Enantiomer or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof provided in step i), in particular the racemate, may be present in different forms, such as crystalline or amorphous free acid form, or a salt thereof, a solvate thereof or a solvate of salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof, e.g. those described in WO 2013 / 127971, WO 2013 / 127968, WO 2021 / 170874, WO 2021 / 170879 or WO 2021 / 170882. The crystalline form may be present in different polymorph and co-crystal forms. Polymorphs are different crystalline forms of the same compound which may have substantially different physicochemical properties, such as solubility, stability, and bioavailability.

[0156] Different methods for examination of polymorphs can be used. Such methods include microscopy, IR-spectroscopy, Raman spectroscopy, Solid-state NMR, TGA, DSC, PXRD, PDF, SCXRD, Electron Diffraction and other techniques. A combination of different techniques can be applied. In particular, PXRD is a powerful technique for examination of polymorphs. X-rays are reflected from crystals only when the angle between the beam and the planes in the crystal satisfies the Bragg condition. There is an infinite number of possible planes in the crystal. Each molecular repetition gives a unique set of reflections and, therefore, generates a unique pattern, which can be recorded as a spectrum. In one embodiment, a mixture comprising Letermovir and R-Enantiomer, in particular the racemate, is provided in step i) in free acid form.

[0157] In one embodiment, a mixture comprising Letermovir and R-Enantiomer, in particular the racemate, is provided in step i) by means of the following steps: a) reacting R-Enantiomer with a C1-C2-alcohol in the presence of an acid to obtain an ester of R-Enantiomer, and b) treating the ester of R-Enantiomer obtained in step a) with a base to obtain a mixture comprising Letermovir and R-Enantiomer.

[0158] In one embodiment, a mixture comprising Letermovir and R-Enantiomer, in particular the racemate, is provided in step i) by means of the following steps: a) reacting R-Enantiomer of Formula (VIII)

[0159] Formula (VIII) with a C1-C2-alcohol in the presence of an acid to obtain an ester of R-Enantiomer of Formula (IX)

[0160]

[0161] Formula (IX) wherein R' is methyl or ethyl, and b) treating the ester of R-Enantiomer of Formula (IX) obtained in step a) with a base to obtain a mixture comprising Letermovir and R-Enantiomer of Formula (X)

[0162] Formula (X).

[0163] In one embodiment said C1-C2-alcohol in step a) is methanol.

[0164] In one embodiment said C1-C2-alcohol in step a) is ethanol.

[0165] In one embodiment, R-Enantiomer is dissolved in said C1-C2-alcohol in step a), wherein the concentration of R-Enantiomer in said C1-C2-alcohol is in the range of from 0.05 M to 0.3 M, preferably from 0.1 to 0.2 M.

[0166] In one embodiment said acid in step a) is selected from the group consisting of sulfuric acid, hydrochloric acid, perchloric acid, nitric acid, a sulfonic acid, such as methanesulfonic acid (MsOH), p-toluenesulfonic acid (TsOH) or trifluoromethanesulfonic acid (TfOH), and a Lewis acid, such as FeCh, TiO(acac)2, Sc(OTf)2, or mixtures thereof. In a preferred embodiment said acid in step a) is selected from the group consisting of sulfuric acid, hydrochloric acid, perchloric acid and nitric acid, or mixtures thereof. In a more preferred embodiment said acid in step a) is sulfuric acid.

[0167] In one embodiment said acid in step a) is added in an amount of from 0.5 to 2.0 equivalents, preferably from 1.0 to 1.5 equivalents with respect to R-Enantiomer.

[0168] In one embodiment, said acid in step a) is selected from the group consisting of sulfuric acid, hydrochloric acid, perchloric acid and nitric acid, wherein said acid is added in an amount of from 1.0 to 1.5 equivalents, preferably from 1.1 to 1.3 equivalents with respect to R-Enantiomer.

[0169] In one embodiment, said acid in step a) is a Lewis acid, such as FeCh, TiO(acac)2, Sc(OTf)2, or mixtures thereof, wherein said acid is added in an amount of from 1.0 to 1.2 equivalents, preferably 1.0 to 1.1 equivalents with respect to R-Enantiomer.

[0170] In one embodiment, step a) is conducted at a temperature in the range of from 60 to 110 °C.

[0171] In one embodiment, step a) is conducted for at least 1 hour. In one embodiment, step a) is conducted for 1 to 96 hours, preferably for 15 to 20 hours.

[0172] In one embodiment, in step a) R-Enantiomer reacts with methanol in the presence of sulfuric acid to obtain a methyl ester of R-Enantiomer, preferably at a temperature in the range of from 60 to 110 °C.

[0173] In one embodiment said base in step b) is selected from the group consisting of alkali hydroxides, alkali earth metal hydroxides, alkoxides, l,5,7-Triazabicyclo[4.4.0]dec-5- ene (TBD) and DBU - l,8-Diazabicyclo[5.4.0]undec-7-ene (DBU). In a preferred embodiment said base in step b) is selected from the group consisting of alkali hydroxides, such as LiOH, NaOH, KOH, CsOH, alkali earth metal hydroxides, such as Ca(OH)2, Sr(OH)2, Ba(OH)2, and alkoxides, such as lithium ethoxide (EtOLi), sodium ethoxide (EtONa), potassium ethoxide (EtOK), lithium isopropoxide (iPrOLi), sodium isopropoxide (iPrONa), potassium isopropoxide (iPrOK), lithium tert-butoxide (tBuOLi), sodium tert-butoxide (tBuONa) and potassium tert-butoxide (tBuOK). In a more preferred embodiment said base in step b) is potassium tert-butoxide (tBuOK) or potassium hydroxide (KOH).

[0174] In one embodiment said base in step b) is added is added in an amount of 1 to 5 equivalents, preferably 1.5 to 4.0 equivalents with respect to the ester of R-Enantiomer.

[0175] In one embodiment, step b) is conducted in a polar aprotic solvent, such as acetonitrile (ACN), dimethylformamide (DMF), 2-methyltetrahydrofuran (2-MeTHF), propionitrile, 1,4-di oxane, chlorobenzene, methyl tert-butyl ether (MTBE), N-methyl-2-pyrrolidone (NMP) or tetrahydrofuran (THF). In one embodiment step b) is conducted in a polar aprotic solvent selected from the group consisting of dimethylformamide, propionitrile and acetonitrile.

[0176] In one embodiment, step b) is conducted at a temperature in the range of from 20 to 110 °C, preferably from 40 to 60 °C.

[0177] In one embodiment, step b) is conducted for at least 10 minutes, preferably for at least 30 minutes. In one embodiment, step b) is conducted for 10 minutes to 96 hours, preferably from 1.5 to 15 hours.

[0178] In one embodiment, step b) is followed by a step of adding an aqueous solution, such as water.

[0179] In one embodiment converting the Letermovir salt of a compound of Formula (I) in step iv-1) is conducted by means of transferring said salt into the compound of Formula (I) and Letermovir, which can be in turn converted to a salt or a solvate or a solvate of salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof, in particular by methods as described in WO 2013 / 127971, WO 2013 / 127968, WO 2021 / 170874, WO 2021 / 170879 or WO 2021 / 170882. The R-Enantiomer salt of a compound of Formula (I) can be converted in a similar way. In one embodiment, said transferring of the Letermovir salt of a compound of Formula (I) is conducted by treating a solution of said salt with an aqueous solution with a pH of from 1 to 4, wherein Letermovir in said salt acts as an acid.

[0180] In one embodiment, said transferring of the R-Enantiomer salt of a compound of Formula (I) is conducted by treating a solution of said salt with an aqueous solution with a pH of from 1 to 4, wherein R-Enantiomer in said salt acts as an acid.

[0181] In one embodiment, said transferring of the Letermovir salt of a compound of Formula (I) is conducted by treating a solution of said salt with an aqueous solution with a pH of from 8 to 12, wherein Letermovir in said salt acts as a base.

[0182] In one embodiment, said transferring of the R-Enantiomer salt of a compound of Formula (I) is conducted by treating a solution of said salt with an aqueous solution with a pH of from 8 to 12, wherein R-Enantiomer in said salt acts as a base.

[0183] In one embodiment, the ratio of Letermovir to R-Enantiomer in said mixture is in the range of from 10:90 to 90: 10, preferably from 20:80 to 80:20, more preferably from 30:70 to 70:30, even more preferably from 40:60 to 60:40, most preferred from 45:55 to 55:45. In a preferred embodiment, said mixture is racemic 2-{(4R,S)8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetic acid or a salt thereof, or a solvate thereof, or a salt of a solvate thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co- crystal thereof or a solvate of a salt of a co-crystal thereof.

[0184] In a more preferred embodiment said mixture is racemic 2-{(4R,S)8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetic acid.

[0185] In one embodiment, step (ii) is carried out in presence of a solvent selected from the group consisting of ketones, such as acetone, methyl ethyl ketone, cyclohexanone, 4- methylcyclohexanone, 4-methyl-2-pentanone or 3 -pentanone; alkanes, such as pentane, hexane, heptane or isooctane; cycloalkanes, such as cyclohexane or cyclopentane; aromatic solvents, such as chlorobenzene, 1,2-di chlorobenzene, cumene, toluene or xylenes; esters such as ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, ethyl propionate, methyl propionate, isoamyl propionate, isobutyl propionate, hexyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, cyclohexyl butyrate, benzyl butyrate, isobutyl formate, ethyl formate, ethyl formate, isopropyl formate, butyl formate, pentyl formate, diethylene glycol monoethyl ether acetate and ethylene glycol diacetate; ethers, such as diisopropyl ether, cyclopentyl methyl ether, butyl ether, diethoxymethane, anisole, ethylene glycol dimethyl ether, diethylene glycol diethyl ether or dimethoxyethane; alcohols such as ethanol, methanol, 2-butanol, isopropanol, n-butanol, diethylene glycol, isobutanol, isopentanol or tert-butanol; nitriles, such as acetonitrile; and carbonates, such as dimethyl carbonate or diethyl carbonate; or mixtures thereof, preferably selected from the group consisting of acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, isoamyl propionate, isobutyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, isoamyl butyrate, diethylene glycol monoethyl ether acetate, ethylene glycol diacetate, cyclohexyl butyrate, benzyl butyrate, diisopropylether, cyclopentyl methyl ether, cumene, isopropanol, 2- butanol, acetonitrile and dimethylcarbonate or mixtures thereof, more preferably selected from the group consisting of acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, isoamyl propionate, isobutyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, isoamyl butyrate, diethylene glycol monoethyl ether acetate, ethylene glycol diacetate, cyclohexyl butyrate, benzyl butyrate, or mixtures thereof, most preferred from the group consisting of pentyl acetate, ethyl butyrate and propyl butyrate or mixtures thereof.

[0186] In one embodiment, said separating in step iii-1) or iii-2) comprises seeding by means of adding between 0.1% and a 10% of crystals, preferably between 0.1% and 5% of crystals, more preferably between 0.1% and 1% of crystals of the less soluble diastereomeric pure salt (prepared beforehand), referred to the total amount of the dissolved solid, to a supersaturated solution of the Letermovir salt of the compound of Formula (I) and an R- Enantiomer of the compound of Formula (I). Depending on the behavior of the formed diastereomeric salts, the temperature and time at which the crystal seeds are added may differ. In one embodiment the seeding is performed having the dissolution at a temperature between 90°C and 0°C. In one embodiment the seeds are added from 1 minute after reaching the seeding temperature (t=l min) to 5 hours after reaching the seeding temperature. In the enantiomeric resolution, the seeding process is particularly effective in promoting the crystallization of the less soluble diastereomeric salt, which may crystallize in a much more controlled fashion improving the yield and providing a better crystallization selectivity with a higher degree of crystallinity and a higher enantiomeric excess in a shorter process time, compared to the resolution without the seeding process.

[0187] In one embodiment, said compound of Formula (I) produces in step ii) diastereomeric salts of Letermovir and R-Enantiomer, which have essentially different solubilities, such as at least 1.1 times, preferably at least 1.2 times, more preferably at least 1.5 times, yet more preferably at least 2 times, yet more preferably at least 2.5 times, most preferred 3.5 times lower in a solvent selected from the group consisting of acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, isoamyl propionate, isobutyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, isoamyl butyrate, diethylene glycol monoethyl ether acetate, ethylene glycol diacetate, cyclohexyl butyrate, benzyl butyrate, diisopropylether, cyclopentyl methyl ether, cumene, isopropanol, 2-butanol, acetonitrile and dimethylcarbonate or mixtures thereof, preferably selected from the group consisting of pentyl acetate, ethyl butyrate and propyl butyrate or mixtures thereof. In one embodiment, diastereomeric salts of Letermovir and R-Enantiomer have from 1.1 to 5 times different solubilities, preferably from 1.5 to 5 times different solubilities, more preferably from 2.5 to 5 times different solubilities, in particular, from 3.5 to 5 times different solubilities.

[0188] In one embodiment, the Letermovir salt of a compound of Formula (I) in step ii) has essentially lower solubility than the R-Enantiomer salt of a compound of Formula (I), such as at least 1.1 times lower, preferably at least 1.2 times lower, more preferably at least 1.5 times lower, yet more preferably at least 2 times lower, yet more preferably at least 2.5 times lower, most preferred 3.5 times lower in a solvent selected from the group consisting of acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, isoamyl propionate, isobutyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, isoamyl butyrate, diethylene glycol monoethyl ether acetate, ethylene glycol diacetate, cyclohexyl butyrate, benzyl butyrate, diisopropylether, cyclopentyl methyl ether, cumene, isopropanol, 2- butanol, acetonitrile and dimethylcarbonate or mixtures thereof, preferably selected from the group consisting of pentyl acetate, ethyl butyrate and propyl butyrate or mixtures thereof. In one embodiment, the Letermovir salt of a compound of Formula (I) in step ii) has from 1.1 to 5 times lower solubility, preferably from 1.5 to 5 times lower solubility, more preferably from 2.5 to 5 times lower solubility, in particular, from 3.5 to 5 times lower solubility than the R-Enantiomer salt of a compound of Formula (I). In a preferred embodiment, said Letermovir salt of a compound of Formula (I) is separated from said solvent as a precipitate, preferably by filtration or centrifugation. In yet another preferred embodiment, said R-Enantiomer salt of a compound of Formula (I) is separated from said solvent as a mother liquor, preferably by filtration or centrifugation. In a preferred embodiment the compound of Formula (I) is a compound of Formula (II) or (III) wherein

[0189] R3 is selected from the group consisting of H, C1-C3-alkyl and phenyl,

[0190] R7 is H or C1-C3-alkyl, R8 is selected from the group consisting of H, OH, methyl or ethyl, wherein R7 and R8, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring.

[0191] In a more preferred embodiment, the compound of Formula (II) is a compound of Formula (Ila) wherein

[0192] R3 is selected from the group consisting of H, C1-C3-alkyl and phenyl,

[0193] R7 is H or C1-C3-alkyl, R8 is H or OH, wherein R7 and R8, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a tetrahydrofuran ring.

[0194] In another more preferred embodiment, the compound of Formula (II) is a compound of Formula (lib) wherein R8 is H, methyl or ethyl.

[0195] In another more preferred embodiment, the compound of Formula (III) is a compound of Formula (Illa) wherein R3 is H, CH2OH or methyl.

[0196] In one embodiment, the R-Enantiomer salt of a compound of Formula (I) in step ii) has essentially lower solubility than the Letermovir salt of a compound of Formula (I), such as at least 1.1 times lower, preferably at least 1.2 times lower, more preferably at least 1.5 times lower, yet more preferably at least 2 times lower, yet more preferably at least 2.5 times lower, most preferred 3.5 times lower solubility in a solvent selected from the group consisting of acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, isoamyl propionate, isobutyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, isoamyl butyrate, diethylene glycol monoethyl ether acetate, ethylene glycol diacetate, cyclohexyl butyrate, benzyl butyrate, diisopropylether, cyclopentyl methyl ether, cumene, isopropanol, 2- butanol, acetonitrile and dimethylcarbonate or mixtures thereof, preferably selected from the group consisting of pentyl acetate, ethyl butyrate and propyl butyrate or mixtures thereof. In one embodiment, the R-Enantiomer salt of a compound of Formula (I) in step ii) has from 1.1 to 5 times lower solubility, preferably from 1.5 to 5 times lower solubility, more preferably from 2.5 to 5 times lower solubility, in particular from 3.5 to 5 times lower solubility, than the Letermovir salt of a compound of Formula (I). In a preferred embodiment, said R-Enantiomer salt of a compound of Formula (I) is separated from said solvent as a precipitate, preferably by filtration or centrifugation. In yet another preferred embodiment, said Letermovir salt of a compound of Formula (I) is separated from said solvent as a mother liquor, preferably by filtration or centrifugation. In a preferred embodiment the compound of Formula (I) is a compound of Formula (IV) or (V)

[0197] (IV) (V) wherein

[0198] R3 is selected from the group consisting of H, C1-C3-alkyl and phenyl,

[0199] R7 is H or C1-C3-alkyl, R8 is selected from the group consisting of H, OH, methyl or ethyl, wherein R7 and R8, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring. In a more preferred embodiment, the compound of Formula (IV) is a compound of Formula (IVa) wherein

[0200] R3 is selected from the group consisting of H, C1-C3-alkyl and phenyl,

[0201] R7 is H or C1-C3-alkyl, R8 is H or OH, wherein R7 and R8, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a tetrahydrofuran ring.

[0202] In another more preferred embodiment, the compound of Formula (IV) is a compound of Formula (IVb) wherein R8 is H, methyl or ethyl.

[0203] In another more preferred embodiment, the compound of Formula (V) is a compound of Formula (Va) wherein R3 is H, CH2OH or methyl. In one embodiment of said method for producing Letermovir or a salt thereof or a solvate thereof or a salt of solvate thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof, the method for producing a Letermovir salt or an R-Enantiomer salt of a compound of Formula (I) or said method for enantiomeric separation the compound of Formula (I) is a compound of Formula (II) or (III)

[0204] (II) (III) wherein

[0205] R3 is selected from the group consisting of H, C1-C3-alkyl and phenyl,

[0206] R7 is H or C1-C3-alkyl, R8 is selected from the group consisting of H, OH, methyl or ethyl, wherein R7 and R8, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein step iii-1) comprises isolating the solid phase comprising the Letermovir salt of the compound of Formula (II) or (III).

[0207] In a preferred embodiment of said method, the compound of Formula (I) is a compound of Formula (II) or (III) as defined above and step (ii) is carried out in a liquid phase in presence of a solvent selected from the group consisting of acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, isoamyl propionate, isobutyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, isoamyl butyrate, diethylene glycol monoethyl ether acetate, ethylene glycol diacetate, cyclohexyl butyrate, benzyl butyrate, diisopropylether, cyclopentyl methyl ether, cumene, isopropanol, 2-butanol, acetonitrile and dimethylcarbonate or mixtures thereof, preferably selected from the group consisting of pentyl acetate, ethyl butyrate and propyl butyrate or mixtures thereof.

[0208] In one embodiment of said method for producing Letermovir or a salt thereof or a solvate thereof or a salt of solvate thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof, the method for producing a Letermovir salt or an R-Enantiomer salt of a compound of Formula (I) or said method for enantiomeric separation the compound of Formula (I) is a compound of Formula (IV) or (V)

[0209] (IV) (V) wherein

[0210] R3 is selected from the group consisting of H, C1-C3-alkyl and phenyl,

[0211] R7 is H or C1-C3-alkyl, R8 is selected from the group consisting of H, OH, methyl or ethyl, wherein R7 and R8, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein step iii-1) comprises isolating the liquid phase comprising the Letermovir salt of the compound of Formula (IV) or (V).

[0212] In a preferred embodiment of said method, the compound of Formula (I) is a compound of Formula (IV) or (V) as defined above and step (ii) is carried out in a liquid phase in presence of a solvent selected from the group consisting of acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, isoamyl propionate, isobutyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, isoamyl butyrate, diethylene glycol monoethyl ether acetate, ethylene glycol diacetate, cyclohexyl butyrate, benzyl butyrate, diisopropylether, cyclopentyl methyl ether, cumene, isopropanol, 2-butanol, acetonitrile and dimethylcarbonate or mixtures thereof, preferably selected from the group consisting of pentyl acetate, ethyl butyrate and propyl butyrate or mixtures thereof.

[0213] In one embodiment of said method for producing Letermovir or a salt thereof or a solvate thereof or a salt of solvate thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof, the method for producing a Letermovir salt or an R-Enantiomer salt of a compound of Formula (I) or said method for enantiomeric separation the compound of Formula (I) is a compound of Formula (IV) or (V)

[0214] (IV) (V) wherein

[0215] R3 is selected from the group consisting of H, C1-C3-alkyl and phenyl,

[0216] R7 is H or C1-C3-alkyl, R8 is selected from the group consisting of H, OH, methyl or ethyl, wherein R7 and R8, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein step iii-2) comprises isolating the solid phase comprising the R-Enantiomer salt of the compound of Formula (IV) or (V). In a preferred embodiment of said method, the compound of Formula (I) is a compound of Formula (IV) or (V) as defined above and step (ii) is carried out in a liquid phase in presence of a solvent selected from the group consisting of acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, isoamyl propionate, isobutyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, isoamyl butyrate, di ethylene glycol monoethyl ether acetate, ethylene glycol diacetate, cyclohexyl butyrate, benzyl butyrate, diisopropylether, cyclopentyl methyl ether, cumene, isopropanol, 2-butanol, acetonitrile and dimethylcarbonate or mixtures thereof, preferably selected from the group consisting of pentyl acetate, ethyl butyrate and propyl butyrate or mixtures thereof.

[0217] In one embodiment of said method for producing Letermovir or a salt thereof or a solvate thereof or a salt of solvate thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof, the method for producing a Letermovir salt or an R-Enantiomer salt of a compound of Formula (I) or said method for enantiomeric separation the compound of Formula (I) is a compound of Formula (II) or (III)

[0218] (II) (III) wherein

[0219] R3 is selected from the group consisting of H, C1-C3-alkyl and phenyl,

[0220] R7 is H or C1-C3-alkyl, R8 is selected from the group consisting of H, OH, methyl or ethyl, wherein R7 and R8, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein step iii-2) comprises isolating the liquid phase comprising the R-Enantiomer salt of the compound of Formula (II) or (III).

[0221] In a preferred embodiment of said method, the compound of Formula (I) is a compound of Formula (II) or (III) as defined above and step (ii) is carried out in a liquid phase in presence of a solvent selected from the group consisting of acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, isoamyl propionate, isobutyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, isoamyl butyrate, di ethylene glycol monoethyl ether acetate, ethylene glycol diacetate, cyclohexyl butyrate, benzyl butyrate, diisopropylether, cyclopentyl methyl ether, cumene, isopropanol, 2-butanol, acetonitrile and dimethylcarbonate or mixtures thereof, preferably selected from the group consisting of pentyl acetate, ethyl butyrate and propyl butyrate or mixtures thereof.

[0222] In a preferred embodiment, the compound of Formula (II) is a compound of Formula (Ila) wherein

[0223] R3 is selected from the group consisting of H, C1-C3-alkyl and phenyl,

[0224] R7 is H or C1-C3-alkyl, R8 is H or OH, wherein R7 and R8, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a tetrahydrofuran ring.

[0225] In another preferred embodiment, the compound of Formula (II) is a compound of Formula (lib) wherein R8 is H, methyl or ethyl.

[0226] In another preferred embodiment, the compound of Formula (III) is a compound of Formula (Illa) wherein R3 is H, CH2OH or methyl.

[0227] In a more preferred embodiment of said method, the compound of Formula (II) is a compound of Formula (Ila) or (lib) and the compound of Formula (III) is a compound of Formula (Illa) as defined above and step (ii) is carried out in a liquid phase in presence of a solvent selected from the group consisting of acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, isoamyl propionate, isobutyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, isoamyl butyrate, diethylene glycol monoethyl ether acetate, ethylene glycol diacetate, cyclohexyl butyrate, benzyl butyrate, diisopropylether, cyclopentyl methyl ether, cumene, isopropanol, 2-butanol, acetonitrile and dimethylcarbonate or mixtures thereof, preferably selected from the group consisting of pentyl acetate, ethyl butyrate and propyl butyrate or mixtures thereof.

[0228] In a more preferred embodiment, the compound of Formula (IV) is a compound of Formula (IVa) wherein

[0229] R3 is selected from the group consisting of H, C1-C3-alkyl and phenyl,

[0230] R7 is H or C1-C3-alkyl, R8 is H or OH, wherein R7 and Rs, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a tetrahydrofuran ring.

[0231] In another more preferred embodiment, the compound of Formula (IV) is a compound of Formula (IVb) wherein Rs is H, methyl or ethyl.

[0232] In another more preferred embodiment, the compound of Formula (V) is a compound of Formula (Va) wherein R3 is H, CH2OH or methyl.

[0233] In a more preferred embodiment of said method, the compound of Formula (IV) is a compound of Formula (IVa) or (IVb) and the compound of Formula (V) is a compound of Formula (Va) as defined above and step (ii) is carried out in a liquid phase in presence of a solvent selected from the group consisting of acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, isoamyl propionate, isobutyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, isoamyl butyrate, diethylene glycol monoethyl ether acetate, ethylene glycol diacetate, cyclohexyl butyrate, benzyl butyrate, diisopropylether, cyclopentyl methyl ether, cumene, isopropanol, 2-butanol, acetonitrile and dimethylcarbonate or mixtures thereof, preferably selected from the group consisting of pentyl acetate, ethyl butyrate and propyl butyrate or mixtures thereof. In one embodiment of said method for producing Letermovir or a salt thereof or a solvate thereof or a salt of solvate thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof, the method for producing a Letermovir salt or an R-Enantiomer salt of a compound of Formula (I) or said method for enantiomeric separation, said method further comprises adding the compound of Formula (II) or (III) as defined above, to said mother liquor comprising said Letermovir salt of a compound of Formula (I) followed by isolating the precipitate comprising the Letermovir salt of the compound of Formula (II) or (III). In a preferred embodiment the compound of Formula (II) is a compound of Formula (Ila) or (lib) as defined above. In another preferred embodiment the compound of Formula (III) is a compound of Formula (Illa) as defined above.

[0234] In another embodiment of said method for producing Letermovir or a salt thereof or a solvate thereof or a salt of solvate thereof or a co-crystal thereof or a solvate of a co- crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof, the method for producing a Letermovir salt or an R-Enantiomer salt of a compound of Formula (I) or said method for enantiomeric separation, said method further comprises adding the compound of Formula (IV) or (V) as defined above, to said mother liquor comprising said R-Enantiomer salt of a compound of Formula (I) followed by isolating the precipitate comprising the R-Enantiomer salt of the compound of Formula (IV) or (V). In a preferred embodiment the compound of Formula (IV) is a compound of Formula (IVa) or (IVb) as defined above. In another preferred embodiment the compound of Formula (V) is a compound of Formula (Va) as defined above.

[0235] In one embodiment, the enantiomeric purity of the compound of Formula (I) is at least 80% ee, preferably et least 85% ee, more preferably at least 90% ee, more preferably at least 95% ee, more preferably at least 98% ee, most preferred at least 99% ee.

[0236] In one embodiment of said method for producing Letermovir or a salt thereof or a solvate thereof or a salt of solvate thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof, the method for producing a Letermovir salt or an R-Enantiomer salt of a compound of Formula (I) or said method for enantiomeric separation the compound of Formula (I) is a compound of Formula (VI) or (VII) wherein R1 is selected from the group consisting of H, C1-C3-alkyl and CH2OH,

[0237] R3 is selected from the group consisting of H, C1-C3-alkyl, phenyl and 4-nitrophenyl,

[0238] R5 and R6 each is independently selected from the group consisting of H and C1-C3-alkyl, preferably each is H,

[0239] R7 is H or C1-C3-alkyl, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C7-oxocyclic ring, and wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring.

[0240] In one embodiment of said method for producing Letermovir or a salt thereof or a solvate thereof or a salt of solvate thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof, the method for producing a Letermovir salt or an R-Enantiomer salt of a compound of Formula (I) or said method for enantiomeric separation the compound of Formula (I) is a compound of Formula (VI) or (VII)

[0241] (VI) (VII) wherein R1 is selected from the group consisting of H, C1-C3-alkyl and CH2OH,

[0242] Rs is selected from the group consisting of H, C1-C3-alkyl, phenyl and 4-nitrophenyl,

[0243] R5 and R6 each is independently selected from the group consisting of H and C1-C3-alkyl, preferably each is H,

[0244] R7 is H or C1-C3-alkyl, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a Cs-Cv-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring and wherein R1 and R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3-C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6- alkenyl, such as 5-ethenyl-l-azabicyclo[2.2.2]octan-2-yl.

[0245] In a preferred embodiment of said method, the compound of Formula (I) is a compound of Formula (VI) or (VII) as defined above and step (ii) is carried out in a liquid phase in presence of a solvent selected from the group consisting of acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, isoamyl propionate, isobutyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, isoamyl butyrate, di ethylene glycol monoethyl ether acetate, ethylene glycol diacetate, cyclohexyl butyrate, benzyl butyrate, diisopropylether, cyclopentyl methyl ether, cumene, isopropanol, 2-butanol, acetonitrile and dimethylcarbonate or mixtures thereof, preferably selected from the group consisting of pentyl acetate, ethyl butyrate and propyl butyrate or mixtures thereof.

[0246] In one embodiment of said method for producing Letermovir or a salt thereof or a solvate thereof or a salt of solvate thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof, the method for producing a Letermovir salt or an R-Enantiomer salt of a compound of Formula (I) or said method for enantiomeric separation the compound of Formula (I), the compound of Formula (I) is selected from the group consisting of (S)-(+)-2 -Amino- 1 -butanol, (2R)-3- amino-2-methoxy-propan-l-ol, (R)-2 -Methoxypropan- 1 -amine, (S)-(+)-2- Amino- 1- hexanol, (S)-(+)-2- Amino- 1 -pentanol, (R)-(-)-2 -Amino- 1 -butanol, L-Phenylalaninol, (1 S,2S)-2-Amino-l-(4-nitrophenyl)-l,3-propanediol, (R)-(-)-2-Phenylglycinol, (R)- (Tetrahydrofuran-2-yl)methanamine, and (1 S,2S)-2-amino-l-phenylpropane-l,3-diol, preferably (S)-(+)-2- Amino- 1 -butanol, (2R)-3-amino-2-m ethoxy-propan- l-ol, (R)-2- Methoxypropan-1 -amine, (S)-(+)-2- Amino- 1 -hexanol, (S)-(+)-2 -Amino- 1 -pentanol, (lS,2S)-2-amino-l -phenylpropane- 1,3 -diol, (R)-[(2S,4S,5R)-5-ethenyl-l- azabicyclo[2.2.2]octan-2-yl](6-methoxyqinolin-4-yl)methanol (quinine) and (S)- [(2R,4S,5R)-5-ethenyl-l-azabicyclo[2.2.2]octan-2-yl](6-methoxyqinolin-4-yl)methanol (quinidine).

[0247] In one embodiment of said method for producing Letermovir or a salt thereof or a solvate thereof or a salt of solvate thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof, the method for producing a Letermovir salt or an R-Enantiomer salt of a compound of Formula (I) or said method for enantiomeric separation the compound of Formula (I), the compound of also depicted with the respective nomenclature in

[0248] Table 1 :

[0249] Table 1

[0250] In one embodiment, the compound of Formula (I) is (S)-(+)-2-Amino-l -butanol and the solvent is pentyl acetate.

[0251] Another aspect of the present invention relates to use of a compound of Formula (I) for producing Letermovir or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof, wherein the compound of Formula (I) is wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxy phenyl, benzyl and CH2OH,

[0252] R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4 -nitrophenyl, quinolinyl and methoxyquinolinyl, R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3-C5-cycloalkyl,

[0253] R? is H or C1-C6-alkyl, wherein R1 and R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R1 and R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3-C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6- alkenyl, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring, in particular by the method as described in the present invention.

[0254] Another aspect of the present invention relates to use of a compound of Formula (I) for producing R-Enantiomer or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof, wherein the compound of Formula (I) is wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxy phenyl, benzyl and CH2OH,

[0255] R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4 -nitrophenyl, quinolinyl and methoxyquinolinyl,

[0256] R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3-C5-cycloalkyl,

[0257] R7 is H or C1-C6-alkyl, wherein R1 and R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R1 and R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form C5-C8-heterobicyclic system, wherein said C3-C6-heterocyclic ring or said Cs-Cs-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6- alkenyl, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring, in particular by the method as described in the present invention.

[0258] Another aspect of the present invention relates to use of a compound of Formula (I) for enantiomeric separation of a mixture comprising Letermovir and R-Enantiomer, or salts thereof or solvates thereof or solvates of salts thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof, wherein the compound of Formula (I) is wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxy phenyl, benzyl and CH2OH,

[0259] R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4 -nitrophenyl, quinolinyl and methoxyquinolinyl,

[0260] R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3-C5-cycloalkyl,

[0261] R7 is H or C1-C6-alkyl, wherein R1 and R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R1 and R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3-C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6- alkenyl, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring, in particular by the method as described in the present invention.

[0262] In one embodiment of said use, the compound of Formula (I) is a compound of Formula (VI) or (VII) R1 is selected from the group consisting of H, C1-C3-alkyl and CH2OH,

[0263] R3 is selected from the group consisting of H, C1-C3-alkyl, phenyl and 4-nitrophenyl,

[0264] R5 and R6 each is independently selected from the group consisting of H and C1-C3-alkyl, preferably each is H,

[0265] R7 is H or C1-C3-alkyl, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C7-oxocyclic ring, and wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring.

[0266] In one embodiment of said use, the compound of Formula (I) is a compound of Formula (VI) or (VII) wherein R1 is selected from the group consisting of H, C1-C3-alkyl and CH2OH,

[0267] R3 is selected from the group consisting of H, C1-C3-alkyl, phenyl and 4-nitrophenyl,

[0268] R5 and R6 each is independently selected from the group consisting of H and C1-C3-alkyl, preferably each is H,

[0269] R7 is H or C1-C3-alkyl, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C7-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein R1 and R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3-C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6- alkenyl, such as 5-ethenyl-l-azabicyclo[2.2.2]octan-2-yl.

[0270] In one aspect, the present invention refers to an R-Enantiomer salt of a compound of Formula (I) wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxy phenyl, benzyl and CH2OH,

[0271] R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4 -nitrophenyl, quinolinyl and methoxyquinolinyl,

[0272] R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3-C5-cycloalkyl,

[0273] R7 is H or C1-C6-alkyl, wherein R1 and R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R1 and R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3-C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6- alkenyl, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring.

[0274] In one embodiment, the present invention refers to an R-Enantiomer salt of a compound of Formula (I), wherein the compound of Formula (I) is a compound of Formula (VI) or (VII) wherein R1 is selected from the group consisting of H, C1-C3-alkyl and CH2OH,

[0275] R3 is selected from the group consisting of H, C1-C3-alkyl, phenyl and 4-nitrophenyl,

[0276] R5 and R6 each is independently selected from the group consisting of H and C1-C3-alkyl,

[0277] R7 is H or C1-C3-alkyl, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C7-oxocyclic ring, and wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring.

[0278] In one embodiment, the present invention refers to an R-Enantiomer salt of a compound of Formula (I), wherein the compound of Formula (I) is a compound of Formula (VI) or (VII) wherein R1 is selected from the group consisting of H, C1-C3-alkyl and CH2OH,

[0279] R3 is selected from the group consisting of H, C1-C3-alkyl, phenyl and 4-nitrophenyl,

[0280] R5 and R6 each is independently selected from the group consisting of H and C1-C3-alkyl,

[0281] R7 is H or C1-C3-alkyl, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a Cs-Cv-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring and wherein R1 and R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3-C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6- alkenyl, such as 5-ethenyl-l-azabicyclo[2.2.2]octan-2-yl.

[0282] In one embodiment, the present invention refers to an R-Enantiomer salt of a compound of Formula (I), wherein said salt is (R)-l-hydroxy-2-methoxypropan-3-aminium salt of 2-{(4R)8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5- (trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetate (1 : 1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 6.0, 9.2, 12.0, 15.2, 17.5, 18.6, 20.4, 21.3, 21.8 and 26.0 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°.

[0283] In one embodiment, the present invention refers to an R-Enantiomer salt of a compound of Formula (I), wherein said salt is (R)-[(2S,4S,5R)-5-ethenyl-l-azabicyclo[2.2.2]octan- 2-yl](6-methoxyqinolin-4-yl)methanol (quinine) salt of 2-{(4R)8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 :1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 5.1, 9.9, 13.3, 13.5, 15.4, 15.7, 16.0, 16.8, 17.2, 18.0, 18.7, 19.1, 20.4, 21.4 and 22.6 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°.

[0284] In one aspect, the present invention refers to a Letermovir salt of a compound of Formula

[0285] (I), wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxy phenyl, benzyl and CH2OH,

[0286] R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4 -nitrophenyl, quinolinyl and methoxyquinolinyl

[0287] R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3-C5-cycloalkyl,

[0288] R7 is H or C1-C6-alkyl, wherein R1 and R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R1 and R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3-C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6- alkenyl, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring.

[0289] In one embodiment, the present invention refers to a Letermovir salt of a compound of Formula (I), wherein the compound of Formula (I) is a compound of Formula (VI) or (VII) wherein R1 is selected from the group consisting of H, C1-C3-alkyl and CH2OH,

[0290] R3 is selected from the group consisting of H, C1-C3-alkyl, phenyl and 4-nitrophenyl,

[0291] R5 and R6 each is independently selected from the group consisting of H and C1-C3-alkyl,

[0292] R7 is H or C1-C3-alkyl, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C7-oxocyclic ring, and wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring.

[0293] In one embodiment, the present invention refers to a Letermovir salt of a compound of Formula (I), wherein the compound of Formula (I) is a compound of Formula (VI) or (VII) wherein R1 is selected from the group consisting of H, C1-C3-alkyl and CH2OH,

[0294] R3 is selected from the group consisting of H, C1-C3-alkyl, phenyl and 4-nitrophenyl,

[0295] R5 and Re each is independently selected from the group consisting of H and C1-C3-alkyl,

[0296] R7 is H or C1-C3-alkyl, wherein R1 and R7, together with the atoms to which they are attached, are optionally connected to form a Cs-Cv-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein R1 and R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3-C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6- alkenyl, such as 5-ethenyl-l-azabicyclo[2.2.2]octan-2-yl.

[0297] In one embodiment, the present invention refers to a Letermovir salt of a compound of Formula (I), wherein the compound of Formula (I) is selected from the group consisting of (R)-(-)-2- Amino- 1 -butanol, L-Phenylalaninol, (lS,2S)-2-Amino-l-(4-nitrophenyl)-

[0298] 1.3 -propanediol, (R)-(-)-2-Phenylglycinol, (S)-(+)-2- Amino- 1 -butanol, (S)-(+)-2- Amino- 1 -hexanol, (S)-(+)-2- Amino- 1 -pentanol, (1 S,2S)-2-amino- 1 -phenyl-propane-

[0299] 1.3-diol, (R)-2-Methoxy propan- 1 -amine, (R)-(Tetrahydrofuran-2-yl)methanamine, (S)- (+)-l-Amino-2-propanol, (S)-(+)-Leucinol and (S)-[(2R,4S,5R)-5-ethenyl-l- azabicyclo[2.2.2]octan-2-yl](6-methoxyqinolin-4-yl)methanol (quinidine).

[0300] In one embodiment, the present invention refers to a Letermovir salt of a compound of selected from the group consisting of respective nomenclature in Table 2:

[0301] Table 2

[0302]

[0303] In one embodiment, the present invention refers to a Letermovir salt of a compound of Formula (I), wherein said salt is (R)-l-hydroxybutan-2-aminium salt of 2-{(4S)-8-fluoro- 2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 :1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 6.1, 8.9, 12.3, 15.3, 16.8, 17.6, 17.9, 20.6, 21.4 and 22.4 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°.

[0304] In one embodiment, the present invention refers to a Letermovir salt of a compound of Formula (I), wherein said salt is (S)-l -hydroxy-3 -phenylpropan-2-aminium salt of 2- {(4S)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5- (trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetate (1 : 1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 5.4, 5.8, 14.3, 14.8, 15.2, 17.8, 18.4, 19.1, 19.5, 19.9, 21.4, 21.8 and 22.2 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°.

[0305] In one embodiment, the present invention refers to a Letermovir salt of a compound of Formula (I), wherein said salt is (lS,2S)-l,3-dihydroxy-l-(4-nitrophenyl)propan-2- aminium salt of 2-{(4S)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy- 5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetate (1 : 1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 5.8, 8.9, 11.7, 14.4, 17.5, 19.2, 19.8, 20.8 and 21.2 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°.

[0306] In one embodiment, the present invention refers to a Letermovir salt of a compound of Formula (I), wherein said salt is (R)-2-hydroxy-l-phenylethan-l-aminium salt of 2-{(4S)- 8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5- (trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetate (1 : 1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 5.6, 5.9, 11.8, 14.5, 15.4, 16.9, 17.5, 18.2, 19.4, 20.5, 21.1 and 21.6 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°.

[0307] In one embodiment, the present invention refers to a Letermovir salt of a compound of Formula (I), wherein said salt is (S)-l-hydroxybutan-2-aminium salt of2-{(4S)-8-fluoro- 2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 :1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 6.1, 8.9, 12.3, 15.2, 17.6, 17.9, 20.6 and 22.3 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°.

[0308] In one embodiment, the present invention refers to a Letermovir salt of a compound of Formula (I), wherein said salt is (S)-l-hydroxyhexan-2-aminium salt of2-{(4S)-8-fluoro- 2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 :1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 6.2, 9.9, 12.4, 13.2, 14.6, 16.6, 18.2, 18.8, 19.8, 20.3, 22.6 and 23.9 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°.

[0309] In one embodiment, the present invention refers to a Letermovir salt of a compound of Formula (I), wherein said salt is (S)-l-hydroxypentan-2-aminium salt of2-{(4S)8-fluoro- 2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 :1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 6.3, 9.9, 12.7, 13.3, 14.8, 16.5, 18.4, 18.8, 20.5, 23.0 and 24.2 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°.

[0310] In one embodiment, the present invention refers to a Letermovir salt of a compound of Formula (I), wherein said salt is (lS,2S)-l,3-dihydroxy-l-phenylpropan-2-aminium salt of 2-{(4S)8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-

[0311] (trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetate (1 : 1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 5.7, 5.8, 9.3, 11.7, 14.5, 15.3, 18.6, 19.4, 20.6 and 21.1 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°.

[0312] In one embodiment, the present invention refers to a Letermovir salt of a compound of Formula (I), wherein said salt is (R)-2-methoxypropan-l-aminium salt of 2-{(4S)8- fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5- (trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetate (1 : 1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 6.0, 9.3, 12.0, 15.2, 17.5, 18.8, 20.4, 21.7 and 25.9 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°. In one embodiment, the present invention refers to a Letermovir salt of a compound of Formula (I), wherein said salt is (R)-(tetrahydrofuran-2-yl)methanaminium salt of 2- {(4S)8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5- (trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetate (1 : 1) said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 6.0, 9.3, 12.0, 15.2, 17.5, 18.7, 20.4 and 21.8 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°.

[0313] In one embodiment, the present invention refers to a Letermovir salt of a compound of Formula (I), wherein said salt is (S)-l-hydroxybutan-2-aminium salt of2-{(4S)-8-fluoro- 2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 :1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 6.0, 9.3, 12.1, 15.3, 18.6, 19.0, 20.6, 21.9 and 22.3 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°.

[0314] In one embodiment, the present invention refers to a Letermovir salt of a compound of Formula (I), wherein said salt is (2S)-l-hydroxy-4-methylpentan-2-aminium salt of 2- {(4S)8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5- (trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetate (1 : 1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 6.3, 9.8, 13.3, 16.2, 18.6, 20.5 and 23.0 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°.

[0315] In one embodiment, the present invention refers to a Letermovir salt of a compound of Formula (I), wherein said salt is (S)-[(2R,4S,5R)-5-ethenyl-l-azabicyclo[2.2.2]octan-2- yl](6-methoxyqinolin-4-yl)methanol (quinidine) salt of 2-{(4S)8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 :1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 4.2, 9.4, 13.4, 14.2, 14.4, 16.5, 16.7, 17.4, 17.7, 18.3, 18.5, 18.8, 19.6, 22.2 and 23.9 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°. In one aspect, the present invention further relates to Letermovir or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co- crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof which is obtainable by the method disclosed herein.

[0316] In one aspect, the present invention further relates to a Letermovir or R-Enantiomer salt of a compound of Formula (I) which is obtainable by a method disclosed herein.

[0317] Abbreviations h hour(s)

[0318] DSC differential scanning calorimetry

[0319] DVS dynamic vapour sorption eq equivalent

[0320] HPLC high pressure liquid chromatography min minutes

[0321] NMR nuclear magnetic resonance

[0322] TGA thermogravimetric analysis

[0323] PXRD powder X-ray diffraction

[0324] 3D-ED electron diffraction

[0325] UPC2 UltraPerformance Convergence Chromatography

[0326] Description of the figures

[0327] Figure 1 shows PXRD analyses of the obtained salts with Letermovir and the R- Enantiomer with both 2-Amino-l -butanol enantiomers.

[0328] Figure 2a shows PXRD of the Letermovir / (R)-(-)-2-Amino-l -butanol salt.

[0329] Figure 2b shows TGA (above) and DSC (below) of the Letermovir / (R)-(-)-2-Amino-l- butanol salt.

[0330] Figure 2c shows DVS of the Letermovir / (R)-(-)-2- Amino- 1 -butanol salt. Figure 3a shows PXRD of the Letermovir / L-Phenylalaninol salt Phase 1.

[0331] Figure 3b shows TGA (above) and DSC (below) of the Letermovir / L-Phenylalaninol salt Phase 1.

[0332] Figure 3c shows DVS of the Letermovir / L-Phenylalaninol salt Phase 1. Figure 3d shows PXRD of the Letermovir / L-Phenylalaninol salt Phase 2.

[0333] Figure 4a shows PXRD of the Letermovir / (lS,2S)-2-Amino-l-(4-nitrophenyl)-l,3- propanediol salt.

[0334] Figure 4b shows TGA (above) and DSC (below) of the Letermovir / (lS,2S)-2-Amino- 1 -(4-nitrophenyl)- 1 ,3 -propanediol salt.

[0335] Figure 4c shows DVS of the Letermovir / (lS,2S)-2-Amino-l-(4-nitrophenyl)-l,3- propanediol salt.

[0336] Figure 5a shows PXRD of the Letermovir / (R)-(-)-2-Phenylglycinol salt.

[0337] Figure 5b shows TGA (above) and DSC (below) of the Letermovir / (R)-(-)-2- Phenylglycinol salt.

[0338] Figure 5c shows DVS of the Letermovir / (R)-(-)-2-Phenylglycinol salt.

[0339] Figure 6a shows PXRD of the Letermovir / (S)-(+)-2- Amino- 1 -butanol salt.

[0340] Figure 6b shows 'H-NMR spectrum of Letermovir / (S)-(+)-2-Amino-l -butanol salt.

[0341] Figure 6c shows TGA (above) and DSC (below) of Letermovir / (S)-(+)-2-Amino-l- butanol salt.

[0342] Figure 6d shows SCXRD of Letermovir / (S)-(+)-2-Amino-l -butanol salt.

[0343] Figure 7a shows PXRD of the Letermovir / (S)-(+)-2- Amino- 1 -hexanol salt.

[0344] Figure 7b shows 'H-NMR spectrum of the Letermovir / (S)-(+)-2- Amino- 1 -hexanol salt.

[0345] Figure 7c shows TGA (above) and DSC (below) of the Letermovir / (S)-(+)-2-Amino-l- hexanol salt.

[0346] Figure 8a shows PXRD of the Letermovir / (S)-(+)-2- Amino- 1 -pentanol salt.

[0347] Figure 9a shows PXRD of the Letermovir / (lS,2S)-2-amino-l-phenyl-propane-l,3-diol salt.

[0348] Figure 10a shows PXRD of the R-Enantiomer / (2R)-3-amino-2-m ethoxy -propan- l-ol salt.

[0349] Figure 10b shows ’H-NMR spectrum of the R-Enantiomer / (2R)-3-amino-2-m ethoxy- propan- l-ol salt.

[0350] Figure 10c shows TGA (above) and DSC (below) of the R-Enantiomer / (2R)-3-amino- 2-m ethoxy-propan- l-ol salt.

[0351] Figure lOd shows SCXRD of the R-Enantiomer / (2R)-3-amino-2-m ethoxy -propan- l-ol salt.

[0352] Figure Ila shows PXRD of the Letermovir / (R)-2-Methoxypropan-l -amine salt.

[0353] Figure 11b shows 'H-NMR spectrum of the Letermovir / (R)-2-Methoxypropan-l -amine salt. Figure 11c shows TGA (above) and DSC (below) of the Letermovir / (R)-2- Methoxypropan-1 -amine salt.

[0354] Figure lid shows SCXRD of the Letermovir / (R)-2-Methoxypropan-l -amine salt.

[0355] Figure 12a shows PXRD of the Letermovir / (R)-(Tetrahydrofuran-2-yl)methanamine salt.

[0356] Figure 12b shows TGA (above) and DSC (below) of the Letermovir / (R)- (T etrahydrofuran-2-yl)methanamine salt.

[0357] Figure 12c shows SCXRD of the Letermovir / (R)-(Tetrahydrofuran-2-yl)methanamine salt.

[0358] Figure 13 shows PXRD of the R-Enantiomer / (R)-(-)-2- Amino- 1 -butanol salt.

[0359] Figure 14 shows PXRD of the R-Enantiomer / (S)-(+)-2- Amino- 1 -butanol salt.

[0360] Figure 15 shows PXRD of the R-Enantiomer / (R)-(-)-2-Phenylglycinol salt.

[0361] Figure 16 shows PXRD of the R-Enantiomer / (R)-(-)-2- Amino- 1 -hexanol salt.

[0362] Figure 17 shows PXRD of the R-Enantiomer / (R)-(-)-2- Amino- 1 -pentanol salt.

[0363] Figure 18 shows PXRD of the R-Enantiomer / (R)-(-)-2- Amino- 1 -propanol salt.

[0364] Figure 19 shows PXRD of the R-Enantiomer / (R)-(-)-l-Amino-2 -propanol salt.

[0365] Figure 20 shows PXRD of the Letermovir / (S)-(+)-l-Amino-2-propanol salt.

[0366] Figure 21 shows PXRD of the R-Enantiomer / (R)-(-)-Leucinol salt.

[0367] Figure 22 shows PXRD of the Letermovir / (S)-(+)-Leucinol salt.

[0368] Figure 23a shows PXRD of the / / -Enantiomer / Quinine salt.

[0369] Figure 23b shows 'H-NMR spectrum of the A-Enantiomer / Quinine salt.

[0370] Figure 23c shows TGA (above) and DSC (below) of the A-Enantiomer / Quinine salt.

[0371] Figure 24a shows PXRD of the Letermovir / Quinidine salt.

[0372] Figure 24b shows 'H-NMR spectrum of the Letermovir / Quinidine salt.

[0373] Figure 24c shows TGA (above) and DSC (below) of the Letermovir / Quinidine salt.

[0374] Figure 25 shows PXRD of amorphous Letermovir obtained in Example 2.10.

[0375] Figure 26a shows PXRD of thejacemic tosylate salt.

[0376] Figure 26b shows TGA (above) and DSC (below) of the racemic tosylate salt.

[0377] Figure 26c shows DVS of the racemic tosylate salt.

[0378] Figure 27a shows PXRD of the racemic calcium salt.

[0379] Figure 27b shows TGA (above) and DSC (below) of the racemic calcium salt.

[0380] Figure 27c shows DVS of the racemic calcium salt.

[0381] Figure 28a shows PXRD of the racemate diphenylurea co-crystal. Figure 28b shows TGA (above) and DSC (below) of the racemate diphenylurea co- crystal.

[0382] Figure 28c shows DVS of the racemate diphenylurea co-crystal.

[0383] The following examples are included to demonstrate preferred embodiments of the invention. It should be appreciated by those of skilled in the art that the techniques disclosed in the examples which follow represent techniques discovered by the inventor to function well in the practice of the invention, and thus can be considered to constitute preferred modes for its practice. However, those of skilled in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention.

[0384] EXAMPLES

[0385] Methods and equipment

[0386] Powder X-Ray Diffraction analysis (PXRD): Approximately 20 mg of sample were prepared in standard sample holders using two foils of polyacetate. The samples were analysed without further manipulation. Powder diffraction patterns were acquired on a D8 Advance Series 2Theta / Theta powder diffraction system using CuKai-radiation (1.54060 A) in transmission geometry. The system was equipped with a VANTEC-1 single photon counting PSD, a Germanium monochromator, a ninety positions autochanger sample stage, fixed divergence slits and a radial soller. The generator intensity for the generation of the X-ray beam is set to 40 mA and 40 kV. Programs used: Data collection with DIFFRAC plus XRD Commander V.2.5.1, and evaluation with High Score Plus 4.9 (Malvern Panalytical). The samples were measured at room temperature in a 0.5 to 1 hour measurement in a range from 4 to 40° in 20 using an angular step of 0.049° and a time per step of 2787 s.

[0387] Proton nuclear magnetic resonance spectroscopy (’H-NMR): Proton nuclear magnetic resonance analyses were recorded in deuterated DMSO (DMSO-tC) in a Bruker Avance 400 Ultrashield NMR spectrometer. Spectra were acquired solving 8 to 10 mg of sample in 0.6 mL of deuterated solvent.

[0388] Differential scanning calorimetry analysis (DSC): Approximately 1 to 4 mg of sample were weighed (using a MX5 Mettler Toledo microbalance) into 40 pL aluminium crucibles with a pinhole lid. DSC analyses were recorded in a Mettler Toledo DSC822e calorimeter. Programs used: Data collection and evaluation with software STARe. The samples were heated under dry nitrogen (flow rate: 50 mL / min) at 10°C / min from 30 to 300°C.

[0389] Thermogravimetric analysis (TGA): Approximately 1 to 10 mg of sample were weighed (using a MX5 Mettler Toledo microbalance) into 40 pL aluminium crucibles with a pinhole lid. Thermogravimetric analyses were recorded in a Mettler Toledo TGA / DSC 3+ with a balance XP1 type. Programs used:

[0390] Data collection and evaluation with software STARe. The samples were heated under dry nitrogen (flow rate: 10 mL / min) at 10°C / min from 30 to 300°C.

[0391] Dynamic Vapour Sorption (DVS): Approximately 10 to 20 mg of sample were weighed into 150 pL platinum crucibles without lid. The experiments were performed in a Mettler Toledo TGA / DSC 1 LF instrument equipped with a LF SDTA FRS2 sensor and coupled with a Modular Humidity Generator MHG 32. Data collection and evaluation was done with STARe software.

[0392] UltraPerformance Convergence Chromatography (UPC2): The enantiomeric excess (%ee) was determined by means of chiral Ultra Performance Convergence Chromatography (UPC2) using two methodologies. The method parameters are available in Table 3:

[0393] Table 3: UPC methodologies

[0394] Electron diffraction (3D-ED)

[0395] Sample preparation: The sample was gently grinded using two glass slides and prepared on a standard copper-graphite grid (Cu200J from JEOL) by lightly contacting the grid with the pulverized sample and removing the excess amount by shaking.

[0396] For the room temperature (RT) measurements: The grid with the sample was mounted on a JEOL standard sample holder.

[0397] For the low temperature samples: The grid with the sample was cryo-prepared on an ELSA sample holder and using the cryo-preparation stage from GATAN. The measurements were performed at 100 K (LT).

[0398] Device: The sample was measured on a XtalLAB Synergy-ED from Rigaku-JEOL provided with a HyPix-ED detector and a LiB6 200 kV electron source (200 kV, 101.20 pA) using shutterless operation. Wavelength: 0.0251 A. Total dose: 5.508e'01e / A2, condenser strength 3, Magnification diffraction: 50 cm, IL1 projection focus: hex 51C1 (21185), CL 10 pm, SA 100 pm, distance (camera length): 644 mm, scan width: 0.25° and exposure time 0.25 s.

[0399] Accessories: ELSA (GATAN) sample holder and sample preparation stage for preparation and measurement of samples at low temperatures.

[0400] Software: CrysAlisPro 43.98a (Rigaku), Olex2 Version 1.5-ac6 (Olex2 vl .5-ac6-012 © OlexSys Ltd. 2004 - 2023).

[0401] Single Crystal X-Ray Diffraction (SCXRD)

[0402] Crystal selection was made using a Zeiss stereomicroscope using polarized light and prepared under inert conditions immersed in perfluoropolyether as protecting oil for manipulation. Crystal structure determination was carried out using a Rigaku diffractometer equipped with a Pilatus 200K area detector, a Rigaku MicroMax-007HF microfocus rotating anode with MoKa radiation, Confocal Max Flux optics and an Oxford Cryosystems low temperature device Cryostream 700 plus (T= -173°C). Full-sphere data collection was used with a> and (p scans. Programs used: Data collection and reduction with CrysAlisPro (Rigaku OD, 2015). V / .60A and absorption correction with Scale3 Abspack scaling algorithm (CrysAlisPro 1.171.39.12b (Rigaku OD, 2015)). Crystal structure solution was achieved using the computer program SHELXT (Sheldrick, G.M. Acta Cryst. 2015 A71, 3-8.) and visualized using the program SHELXle (C.B. Huebschle, G.M. Sheldrick & B. Dittrich; J.Appl.Cryst., 2011 44, 1281-1284). Missing atoms were subsequently located from difference Fourier synthesis and added to the atom list. Least- squares refinement on Fo2using all measured intensities was carried out using the program SHELXL 2015 (SHELXL; Sheldrick, G.M. Acta Cryst., 2015 A71, 3-8.). All non- hydrogen atoms were refined including anisotropic displacement parameters.

[0403] Example 1. Preparation of pure chiral salts of Letermovir and R-Enantiomer with chiral aminoalcohols.

[0404] Experimental procedure: A suspension / solution of Letermovir or the R-Enantiomer and the respective chiral agent at 75°C was prepared. The suspensions were stirred for 1 to 2 hours, then cooled down to room temperature and stirred for 15 hours. The obtained solid was filtered off, washed with the respective solvent and dried under vacuum.

[0405] Table 4 shows the salts that were prepared with 1,2-aminoalcohol derivatives and the solvents used. In the case of 2- Amino- 1 -butanol, all the possible stereoisomers (S / S, R / R, S / R and R / S) were successfully prepared and compared. PXRD analyses are available in Figure 1.

[0406] Table 4: Preparation of pure chiral salts of 1,2-aminoalcohol derivatives

[0407] It must be noted that the results that afford R / R and S / R salts are equivalent (but mirrored) to those affording S / S and R / S salts. That means, if a specific chiral agent (5) provides Letermovir, the same chiral agent (R) will provide the R-Enantiomer. Thus, all the results with R chiral agents can be translated to the S chiral agents but inverting the chirality of the enantiomer obtained.

[0408] Characterization of the obtained salts

[0409] Letermovir / (R)-(-)-2- Amino- 1 -butanol salt

[0410] Table 5: Characterization of Letermovir / (R)-(-)-2-Amino-l -butanol salt

[0411] Table 6: Peak List for the PXRD analysis of the Letermovir / (R)-(-)-2- Amino- 1 -butanol salt

[0412] Letermovir / L-Phenylalaninol salt Phase 1

[0413] Table 7: Characterization of Letermovir / L-Phenylalaninol salt Phase 1

[0414] Table 8: Peak List for the PXRD analysis of the Letermovir / L-Phenylalaninol salt Phase Letermovir / L-Phenylalaninol salt Phase 2

[0415] Table 9: Characterization of Letermovir / L-Phenylalaninol salt Phase 2

[0416] Table 10: Peak List for the PXRD analysis of the Letermovir / L-Phenylalaninol salt

[0417] Phase 2

[0418] Letermovir / (lS,2S)-2-Amino-l-(4-nitrophenyl)-L3-propanediol salt

[0419] Table 11: Characterization of Letermovir / (lS,2S)-2-Amino-l-(4-nitrophenyl)-l,3- propanediol salt Table 12: Peak List for the PXRD analysis of the Letermovir / (lS,2S)-2-Amino-l-(4- nitrophenyl)- 1 , 3 -propanediol salt

[0420] Letermovir / (R)-(-)-2-Phenylglycinol Table 13: Characterization of the Letermovir / (R)-(-)-2-Phenylglycinol salt

[0421] Table 14: Peak List for the PXRD analysis of the Letermovir / (R)-(-)-2-Phenylglycinol salt

[0422] Letermovir / (X)-(+)-2- Amino- 1 -butanol salt

[0423] Table 15: Characterization of the Letermovir / (5)-2-Amino-l -butanol salt

[0424] Table 16: Peak List for the PXRD analysis of the Letermovir / (5)-2- Amino- 1 -butanol salt Table 17: Crystal data and structure refinement for the Letermovir / S-(+)-2- Amino- 1- butanol salt

[0425] Letermovir / (S)-(+)-2- Amino- 1 -hexanol salt

[0426] Table 18: Characterization of the Letermovir / (5)-2-Amino-l -hexanol salt

[0427] Table 19: Peak List for the PXRD analysis of the Letermovir / (5)-2- Amino- 1 -hexanol salt Letermovir / (S)-(+)-2- Amino- 1 -pentanol salt

[0428] Table 20: Characterization of the Letermovir / (5)-2-Amino-l -pentanol salt

[0429] Table 21: Peak List for the PXRD analysis of the Letermovir / (5)-2- Amino- 1 -pentanol salt Letermovir / (lS,2S)-2-amino-l-phenyl-propane-L3-diol salt

[0430] Table 22: Characterization of the Letermovir / (75,25)-2-amino-l-phenyl-propane-l,3-diol salt

[0431] Table 23: Peak List for the PXRD analysis of the Letermovir / (75, 25)-2-amino-l -phenyl- propane- 1,3 -diol salt

[0432] R-Enantiomer / (2R)-3-amino-2-methoxy -propan- l-ol salt

[0433] Table 24: Characterization of the R-Enantiomer / (2A’)-3-amino-2-m ethoxy -propan- l-ol salt

[0434] Table 25: Crystal data and structure refinement for the R-Enantiomer / (2A’)-3-amino-2- methoxy-propan-l-ol salt

[0435] Table 26: Peak List for the PXRD analysis of the R-Enantiomer / (2A’)-3-amino-2-m ethoxy- propan- l-ol salt Letermovir / (R)-2-Meth oxypropan- 1 -amine salt

[0436] Table 27: Characterization of the_Letermovir / (7?)-2 -Methoxypropan- 1 -amine salt

[0437] Table 28: Peak List for the PXRD analysis of the Letermovir / (7?)-2 -Methoxypropan- 1 -amine salt Table 29: Crystal data and structure refinement for the Letermovir / (A)-2 -Methoxypropan- 1 - amine

[0438] Letermovir / (R)-(Tetrahy drofuran -2 -yl)m ethanamine salt

[0439] Table 30: Characterization of the Letermovir / (A)-(Tetrahydrofuran-2-yl)methanamine salt

[0440] Table 31: Peak List for the PXRD analysis of the Letermovir / ( / ?)-(Tetrahydrofuran-2- yl)methanamine salt

[0441] Table 32: Crystal data and structure refinement for the Letermovir / (R)-(Tetrahydrofuran-2- yl)methanamine salt

[0442] R-Enantiomer / (R)-(-)-2- Amino- 1 -butanol salt

[0443] Table 33: Characterization of the R-Enantiomer / (R)-(-)-2-Amino-l -butanol salt

[0444] Table 34: Peak List for the PXRD analysis of the R-Enantiomer / (R)-(-)-2-Amino-l -butanol salt

[0445] R-Enantiomer / (S)-(+)-2- Amino- 1 -butanol salt

[0446] Table 35: Characterization of the R-Enantiomer / (S)-(+)-2-Amino-l -butanol salt Table 36: Peak List for the PXRD analysis of the R-Enantiomer / (S)-(+)-2- Amino- 1 -butanol salt

[0447] R-Enantiomer / (R)-(-)-2-Phenylglycinol salt

[0448] Table 37: Characterization of the R-Enantiomer / (R)-(-)-2-Phenylglycinol salt

[0449] Table 38: Peak List for the PXRD analysis of the R-Enantiomer / (R)-(-)-2-Phenylglycinol salt

[0450] R-Enantiomer / (R)-(-)-2- Amino- 1 -hexanol salt

[0451] Table 39: Characterization of the R-Enantiomer / (R)-(-)-2-Amino-l -hexanol salt

[0452] Table 40: Peak List for the PXRD analysis of the R-Enantiomer / (R)-(-)-2- Amino- 1 -hexanol salt

[0453] R-Enantiomer / (R)-(-)-2- Amino- 1 -pentanol salt

[0454] Table 41: Characterization of the R-Enantiomer / (R)-(-)-2-Amino-l -pentanol salt Table 42: Peak List for the PXRD analysis of the R-Enantiomer / (R)-(-)-2 -Amino- 1 -pentanol salt

[0455] R-Enantiomer / (R)-(-)-2- Amino- 1 -propanol salt

[0456] Table 43: Characterization of the R-Enantiomer / (R)-(-)-2-Amino-l -propanol salt

[0457] Table 44: Peak List for the PXRD analysis of the R-Enantiomer / (R)-(-)-2- Amino- 1 -propanol salt

[0458] R-Enantiomer / (R)-(-)-l-Amino-2-propanol salt

[0459] Table 45: Characterization of the R-Enantiomer / (R)-(-)-l-Amino-2-propanol salt

[0460] Table 46: Peak List for the PXRD analysis of the R-Enantiomer / (R)-(-)-l-Amino-2-propanol salt

[0461] Letermovir / (S)-(+)-l-Amino-2-propanol salt

[0462] Table 47: Characterization of the Letermovir / (S)-(+)-l-Amino-2 -propanol salt

[0463] Table 48: Peak List for the PXRD analysis of the Letermovir / (S)-(+)-l-Amino-2-propanol salt

[0464] R-Enantiomer / (R)-(-)-Leucinol salt

[0465] Table 49: Characterization of the R-Enantiomer / (R)-(-)-Leucinol salt

[0466] Table 50: Peak List for the PXRD analysis of the R-Enantiomer / (R)-(-)-Leucinol salt

[0467] Letermovir / (S)-(+)-Leucinol salt

[0468] Table 51: Characterization of the Letermovir / (S)-(+)-Leucinol salt

[0469] Table 52: Peak List for the PXRD analysis of the Letermovir / (S)-(+)-Leucinol salt

[0470] A’-Enantiomer / -r(2X4X57?)-5-ethenyl-l-azabicyclor2.2.21octan-2-yl1(6-methoxyqinolin- 4-yl)methanol (quinine) salt

[0471] Table 53: Characterization of the A’-Enantiomer / (7?)-[(25,45,57?)-5-ethenyl-l- azabicyclo[2.2.2]octan-2-yl](6-methoxyqinolin-4-yl)methanol (quinine) salt

[0472] Table 54: Peak List for the PXRD analysis of the A’-Enantiomer / (7?)-[(25',45',57?)-5-ethenyl-l- azabicyclo[2.2.2]octan-2-yl](6-methoxyqinolin-4-yl)methanol (quinine) salt

[0473] Letermovir / (y)-r(27?,4X57?)-5-ethenyl-l-azabicyclor2.2.21octan-2-yl1(6-methoxyqinolin-4- vDmethanol (quinidine) salt

[0474] Table 55: Characterization of the Letermovir / (5)-[(27?,45,57?)-5-ethenyl-l- azabicyclo[2.2.2]octan-2-yl](6-methoxyqinolin-4-yl)methanol (quinidine) salt

[0475] Table 56: Peak List for the PXRD analysis of the Letermovir / (k)-[(2 / ?,4k,5 / ?)-5-ethenyl- l - azabicyclo[2.2.2]octan-2-yl](6-methoxyqinolin-4-yl)methanol (quinidine) salt

[0476] Solubility assessment

[0477] Solubility assessments in isobutyl acetate showed that the S / S and R / R enantiomeric pairs of Letermovir and R-Enantiomer with 1,2-aminoalcohols are surprisingly significantly less soluble than their respective diastereomers (R / S and S / R). This suggests that chiral aminoalcohols may be especially suited for enantiomeric resolution via selective crystallization.

[0478] Example 2. Enantiomeric resolution

[0479] General procedures for the enantiomeric resolution Procedure 1 : Direct enantiomeric resolution

[0480] A 200 to 700 mg / mL (500 mg / mL) solution / suspension of the racemic 2-{(4R,S)-8-fluoro-2- [4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetic acid, or a basic or an acidic salt thereof, or a solvate thereof or a solvate of a salt thereof, or a co-crystal thereof, or a solvate of a co-crystal thereof, or a co- crystals of a salt thereof, or a solvate of a co-crystal of a salt thereof is prepared in the respective solvent at 40 tolOO°C (85°C). Then, 0.5 to 10 eq (preferably 1.1 eq if the free racemate or a co- crystal or a solvate of the racemate is used; 2 eq if an acidic or basic salt of the racemate is used) of the aminoalcohol or the aminoether are added directly or as a 50 to 400 mg / mL solution (150 mg / mL) in the respective solvent. When an acidic salt of the racemate is used, additional 0.5 to 1.5 eq of a non-chiral base (e.g. triethylamine, isopropylamine, butylamine or diethylamine) may be added. The obtained solution / suspension is cooled down to 25 to 85°C (75°C). At this point, the solution / suspension may be seeded with the pure less soluble diastereomeric salt. 1 to 10 temperature cycles of heating and cooling may be applied at this stage.

[0481] The solution / suspension is then stirred for 0.5 to 4 hours (2 hours) and allowed to cool down to room temperature for 3 to 24 hours (4 hours) whilst stirring. The obtained solid (Letermovir salt) is filtered off, washed with the respective solvent and dried under vacuum (2 to 20 mbar) for 5 to 48 hours (15 hours).

[0482] Procedure 2: Inverse enantiomeric resolution

[0483] A 200 to 700 mg / mL (500 mg / mL) solution / suspension of the racemic 2-{(4R,S)-8-fluoro-2- [4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetic acid or a basic or an acidic salt thereof, or a solvate thereof or a solvate of a salt thereof, or a co-crystal thereof, or a solvate of a co-crystal thereof, or a co-crystals of a salt thereof, or a solvate of a co-crystal of a salt thereof is prepared in the respective solvent at 40 to 100°C (85°C). Then, 0.5 to 10 eq (preferably 1.1 eq if the free racemate or a co-crystal or a solvate of the racemate is used; 2 eq if an acidic or basic salt of the racemate is used) of the aminoalcohol or the aminoether are added directly or as a 50 to 400 mg / mL solution (150 mg / mL) in the respective solvent. The obtained solution / suspension is cooled down to 25 to 85°C (75°C). At this point, the solution / suspension may be seeded with the pure less soluble diastereomeric salt. The solution / suspension is then stirred for 0.5 to 4 hours and allowed to cool down to room temperature for 5 to 24 hours (15 hours) whilst stirring. The solid (R-Enantiomer salt) is then separated by filtration and the solution (enriched with Letermovir) is subjected to a work-up, which can be either work-up 1 or work-up 2:

[0484] Work-up 1: The aminoalcohol or the aminoether of the solution is extracted with an acetate buffer (pH 3 to 4). The aqueous phase is discarded. The organic phase is washed 1 to 3 times with water. Procedure 1 is applied to the resulting Letermovir enriched solution.

[0485] Work-up 2: Procedure 1 is directly applied without removing the aminoalcohol or the aminoether.

[0486] Cooling: Whilst stirring, lowering the temperature of the solution / suspension at a rate of 0.1 to 20°C / min

[0487] Heating: Whilst stirring, raising the temperature of the solution / suspension at a rate of 0.1 to 20°C / min

[0488] Temperature Cycle: Heating followed by a Cooling procedure, or vice versa. The cycles can be repeated, and the temperature ranges modified in each cycle. The temperature ranges may be between 90°C and 0°C.

[0489] Procedure 3 : Release of the Letermovir free base from the chiral salt

[0490] The chiral salt of Letermovir or the R-Enantiomer was dissolved in dichloromethane (concentration: 100 to 500 mg / mL) and extracted 1 to 5 times with < 0.1 M acetate buffer (pH = 3 to 4). The organic phase was then evaporated under reduced pressure, and the white foamy residue was dissolved in acetone (final concentration: 100 to 500 mg / mL) and precipitated via addition of water (final ratio: 1 :5 - 1 :20 acetone / water). The suspension was stirred for 15 to 60 hours, filtered off and then dried under vacuum, affording a white solid.

[0491] Procedure 4: Solid-state enantiomeric resolution

[0492] The racemic 2-{(4R,S)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5- (trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetic acid or a basic or an acidic salt thereof, or a solvate thereof or a solvate of a salt thereof, or a co-crystal thereof, or a solvate of a co-crystal thereof, or a co-crystals of a salt thereof, or a solvate of a co-crystal of a salt thereof and 1 to 10 equivalents of the respective chiral agent were mixed and grinded in a ball mill (5 to 120 minutes, frequency 5 to 30 s'1). A catalytic amount of a given solvent, such as ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate isobutyl acetate, acetonitrile, isopropanol or pentyl acetate may be added (1 to 100 pL) before the grinding procedure.

[0493] The obtained solids were suspended in ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate isobutyl acetate or pentyl acetate (preferably pentyl acetate, final concentration ca. 100 to 500 mg / mL, stirred for 0.5 to 15 hours at room temperature, filtered off, washed 1 to 3 times with pentyl acetate and dried under vacuum.

[0494] Procedure 5: Letermovir free base release (liquid-liquid extraction)

[0495] The chiral salt of Letermovir or the R-Enantiomer was dissolved in dichloromethane (concentration: 100 - 500 mg / mL) and extracted 1 to 5 times with < 0.1 M acetate buffer (pH 3 to 4). The organic phase was then evaporated under reduced pressure to afford Letermovir as a foamy, resinous solid.

[0496] Procedure 6: Precipitation of amorphous Letermovir

[0497] Direct antisolvent addition:

[0498] The Letermovir free base was dissolved in a solvent or solvent mixture (concentration 100 - 1000 mg / mL). Then, 1 to 20 volumes, preferably 5 to 10 volumes, of an antisolvent or antisolvent mixture were added. The obtained suspension was stirred for 3 to 60 hours, preferably ca 15 hours. The obtained off-white solid was filtered off and dried under vacuum (3 to 100 mBar, 40 to 70°C, 2 to 15 hours).

[0499] Inverse antisolvent addition:

[0500] To 2 to 20 volumes of a given antisolvent, a solution of Letermovir in a given solvent (concentration 400 - 1200 mg / mL, preferably 800 mg / mL), was slowly added whilst stirring (controlled addition via syringe pump). The suspension was stirred for 3 to 60 hours, preferably 15 hours, filtered off and dried under vacuum (3 to 100 mBar, 40 to 70°C, 2 to 15 hours).

[0501] The results of the experiments are summarized in Tables 57 and 58. Table 57: Selection of solvent and antisolvent pairs which afford amorphous Letermovir.

[0502] The amorphous nature of the obtained product was confirmed by PXRD for all the performed experiments. The PXRD data is in all cases identical and matches the PXRD pattern as depicted in Figure 25.

[0503] Table 58: Selection of results using 1,2-aminoalcohols and 1,2-aminoethers.

[0504] Yields are expressed with respect to the racemate (maximum yield for a perfect resolution through crystallization of one enantiomer: 50%). % ee values may refer to an excess of the R- Enantiomer (R) or to an excess of Letermovir (Let).

[0505] Example 2.1: (S)-(+)-2-Amino-l-butanol / butyl acetate (90 hours)

[0506] Experimental procedure: A 160 mg / mL solution of (S)-(+)-2- Amino- 1 -butanol in butyl acetate (80 mg in 0.5 mL) was added over 1 eq of a 500 mg / mL solution (500 mg in 1 mL) of the racemic 2-{(4R,S)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-

[0507] (trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetic acid in butyl acetate at 75°C. The solution was seeded with Letermovir / (S)-(+)-2- Amino- 1 -butanol salt, then stirred for 1 hour and allowed to cool down for 90 hours whilst stirring. The obtained solid was filtered off, washed with butyl acetate (0.5 mL, twice) and dried under vacuum overnight (2 to 3 mBar, 50°C). 242 mg of crystalline Letermovir / (S)-(+)-2-Amino-l -butanol salt were obtained (42% with respect to the racemate, enantiomeric excess: 79%).

[0508] Example 2.2: (S)-(+)-2-Amino-l-butanol / pentyl acetate (15 hours)

[0509] Experimental procedure: A 160 mg / mL solution of (S)-(+)-2- Amino- 1 -butanol in pentyl acetate (80 mg in 0.5 mL) was added over 1 eq of a 500 mg / mL solution (500 mg in 1 mL) of the racemic 2-{(4R,S)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-

[0510] (trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetic acid in pentyl acetate at 85°C. The solution was cooled down to 70 to 80°C and seeded with Letermovir / (S)-(+)-2 -Amino- 1- butanol salt, then stirred for 1 hour and allowed to cool down for 15 hours whilst stirring. The obtained solid was filtered off, washed with pentyl acetate (0.5 mL, twice) and dried under vacuum overnight (2 to 3 mBar, 50°C). 225 mg of crystalline Letermovir / (S)-(+)-2-Amino-l- butanol salt were obtained (39% with respect to the racemate, enantiomeric excess: 95%).

[0511] Example 2.3: (R)-(-)-2-Amino-l-pentanol / pentyl acetate (15 hours)

[0512] Experimental procedure: An 80 mg / mL solution of (R)-2-Amino-l -pentanol in pentyl acetate (40 mg in 0.5 mL) was added over 1 eq of a 500 mg / mL solution (250 mg in 0.5 mL) of the racemic 2-{(4R,S)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-

[0513] (trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetic acid in pentyl acetate at 85°C. The solution was cooled down to 50°C and seeded with pure R-Enantiomer / (R)-2-Amino-l- pentanol salt, then stirred for 1 hour and allowed to cool down for 15 hours whilst stirring. The obtained solid was filtered off, washed with pentyl acetate (0.5 mL) and dried under vacuum overnight (2 to 3 mBar, 50°C). 87 mg of crystalline R-Enantiomer / (R)-2-Amino-l -pentanol saltwere obtained (30% with respect to the racemate, enantiomeric excess: 94%).

[0514] Example 2.4: Inverse resolution. 1) (R)-(-)-2-Amino-l-butanol, 2) (S)-(+)-2-Amino-l- butanol / pentyl acetate

[0515] Experimental procedure: The racemic 2- {(4R,S)-8 -fluoro-2-[4-(3 -methoxy phenyl)piperazin- 1- yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetic acid (1 g) and 1 eq of (R)-(-)-2- Amino- 1 -butanol (160 mg) were dissolved in pentyl acetate at 85°C (concentration of the racemate 200 mg / mL). The solution was cooled down to 75°C and seeded with the R-Enantiomer / (R)-(-)-2-Amino-l -butanol salt.

[0516] The suspension was cooled down to 65°C, then heated up to 85°C and finally cooled down to room temperature and slurried for 15 hours.

[0517] The suspension was filtered off and washed with pentyl acetate (0.5 mL, twice). 441 mg of the R-Enantiomer / (R)-(-)-2-Amino-l -butanol salt were obtained (38% with respect to the racemate, enantiomeric excess: >95%).

[0518] The mother liquor was extracted with 10 mL of HC1 0.15 M, then washed with 10 mL of water and dried with CaCL. The resulting yellow solution was then reacted with 78 mg of (S)-(+)-2- Amino-1 -butanol salt (1 eq with respect to the theoretical remaining Letermovir in solution), seeded at room temperature with Letermovir / (S)-(+)-2- Amino- 1 -butanol salt and allowed to slurry overnight.

[0519] The suspension was filtered off and washed with pentyl acetate (0.5 mL, twice). 100 mg of Letermovir / (S)-(+)-2- Amino- 1 -butanol salt were obtained (18% with respect to the racemate, enantiomeric excess: 94%).

[0520] Example 2.5: (S)-(+)-2-Amino-l-butanol / pentyl acetate (heating-cooling cycles, 24 hours) Experimental procedure: The racemic 2- {(4R,S)-8 -fluoro-2-[4-(3 -methoxy phenyl)piperazin- 1- yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetic acid (1 g) and 1 eq of (S)-(+)-2- Amino- 1 -butanol were dissolved in 3 mL of pentyl acetate at 85°C. The solution was cooled down to 70°C and seeded with Letermovir / (S)-(+)-2- Amino- 1 -butanol salt, then subjected to the following heating-cooling cycles:

[0521] • 1stCycle: Heating to 85°C, then cooling down to 30 to 35°C (ca. 1 hour).

[0522] • 2ndCycle: Heating to 85°C, then cooling down to 30 to 35°C (ca. 1 hour). • 3rdCycle: Heating to 85°C, then cooling down to 30 to 35°C and slurry overnight (ca. 15 hours).

[0523] • 4thCycle: Heating to 85°C, then cooling down to 30 to 35°C (ca. 1 hour).

[0524] • 5thCycle: Heating to 85°C, then cooling down to 30 to 35°C (ca. 1 hour).

[0525] The obtained solid was filtered off, washed with pentyl acetate (0.5 mL, twice) and dried under vacuum (2 to 3 mBar, 50°C, 15 hours). 457 mg of crystalline Letermovir / (S)-(+)-2-Amino-l- butanol salt were obtained (40% with respect to the racemate; enantiomeric excess: 95%).

[0526] Example 2.6: (S)-2-Methoxypropan-l-amine / pentyl acetate (cooling-heating cycle, 6 hours)

[0527] Experimental procedure: The racemic 2- {(4R,S)-8 -fluoro-2-[4-(3 -methoxy phenyl)piperazin- 1- yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetic acid (1 g) and 1.1 eq of (S)-2-Methoxypropan-l -amine were dissolved in 3 mL of pentyl acetate at 90°C (concentration of the racemate: 333 mg / mL).

[0528] The solution was cooled down to 60 to 70°C, seeded with the R-Enantiomer / (S)-2- Methoxypropan-1 -amine salt, cooled down to 35°C, then subjected to one heating-cooling cycle (heating to 60 to 70°C, followed by cooling to room temperature). The solution was stirred for 3 hours, filtered off, washed with pentyl acetate (0.5 mL, three times) and dried under vacuum overnight. 416 mg of crystalline Letermovir / (S)-2 -Methoxypropan- 1 -amine salt were obtained (36% with respect to the racemate; enantiomeric excess: 99%).

[0529] Example 2.7: (S)-(+)-2-Amino-l-butanol salt / pentyl acetate (solid state enantiomeric resolution.

[0530] Experimental procedure: The racemic 2- {(4R,S)-8 -fluoro-2-[4-(3 -methoxy phenyl)piperazin- 1- yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetic acid (100 mg) and 1.1 eq of (S)-(+)-2-Amino-l -butanol (20 mg) were grinded in a ball mill for 15 minutes at a 15 s'1frequency. A catalytic amount (ca. 50 pL) of pentyl acetate was added to the mixture before the grinding procedure (LAG: liquid assisted grinding).

[0531] The obtained resinous residue was then suspended in 0.2 mL of pentyl acetate and stirred for 1 hour at room temperature. The solvent was decanted, and the resulting white powder was washed with 0.2 mL of pentyl acetate. Ca. 30 mg of solid of crystalline Letermovir / (S)-(+)-2- Amino- 1 -butanol salt were obtained (25% with respect to the racemate; enantiomeric excess: 81%).

[0532] Example 2.8: (R)-2-Methoxypropan-l-amine salt / pentyl acetate (solid state enantiomeric resolution

[0533] Experimental procedure: The racemic 2- {(4R,S)-8 -fluoro-2-[4-(3 -methoxy phenyl)piperazin- 1- yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetic acid (100 mg) and 1.1 eq of (R)-2-Methoxypropan-l -amine (18 mg) were grinded in a ball mill for 15 minutes at a 15 s'1frequency. A catalytic amount (ca. 50 pL) of pentyl acetate was added to the mixture before the grinding procedure (LAG: liquid assisted grinding).

[0534] The obtained resinous residue was then suspended in 0.2 mL of pentyl acetate and stirred for 1 hour at room temperature. The solvent was decanted, and the resulting white powder was washed with 0.2 mL of pentyl acetate. Ca. 30 mg of solid of crystalline Letermovir / (R)-2- Methoxypropan-1 -amine salt were obtained (25% with respect to the racemate; enantiomeric excess: 75%).

[0535] Example 2.9: Letermovir Free Base release from the Letermovir / (S)-(+)-2-Amino-l- butanol salt (liquid - liquid extraction)

[0536] Experimental procedure: The Letermovir / (S)-(+)-2-Amino-l -butanol salt (1.5 g) was dissolved in 15 mL of di chloromethane. The organic phase was extracted twice with 20 mL of an acetate buffer (pH = 4), and the aqueous phase was extracted once with 20 mL of di chloromethane. The organic solution was evaporated to dryness in a rotary evaporator, affording 1.38 g (>99% yield) of Letermovir free base as a foamy, resinous solid.

[0537] Example 2.10: Letermovir Free Base precipitation

[0538] Experimental procedure: The Letermovir free base (150 mg) was dissolved in 0.5 mL of acetone. 5 mL of water were added (1 : 10 acetone / water ratio). The obtained suspension was stirred for 15 hours. The obtained off-white solid was filtered off and dried under vacuum (3 to 5 mBar, 40°C, 15 hours). 128 mg of solid Letermovir free base (85% yield) were obtained. PXRD confirmed the amorphous nature of the obtained solid product (see Figure 25).

[0539] Example 2.11: (5)-(+)-2-Amino-l-butanol salt / ethyl acetate (solid state enantiomeric resolution) Experimental procedure: The racemic 2- {(4R,S)-8 -fluoro-2-[4-(3 -methoxy phenyl)piperazin- 1- yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetic acid (200 mg) and 1 eq of (5)-(+)-2- Amino- 1 -butanol were grinded in a ball mill for 60 minutes at a 30 s'1frequency. A catalytic amount (ca. 50 pL) of ethyl acetate was added to the mixture before the grinding procedure (LAG: liquid assisted grinding).

[0540] The obtained mixture was then suspended in 0.5 mL of pentyl acetate and stirred for 30 minutes at room temperature. The resulting suspension was filtered off and washed with 0.5 mL of pentyl acetate, affording ca. 75 mg of crystalline Letermovir / (S)-(+)-2- Amino- 1 -butanol salt (yield: 29% with respect to the racemate, enantiomeric excess: 84%).

[0541] Example 2.12: (5)-(+)-2-Amino-l-butanol salt / acetonitrile (solid state enantiomeric resolution)

[0542] Experimental procedure: The racemic 2- {(4R,S)-8 -fluoro-2-[4-(3 -methoxy phenyl)piperazin- 1- yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetic acid (200 mg) and 1 eq of (5)-(+)-2- Amino- 1 -butanol were grinded in a ball mill for 60 minutes at a 30 s'1frequency. A catalytic amount (ca. 50 pL) of acetonitrile was added to the mixture before the grinding procedure (LAG: liquid assisted grinding).

[0543] The obtained mixture was then suspended in 0.5 mL of pentyl acetate and stirred for 30 minutes at room temperature. The resulting suspension was filtered off and washed with 0.5 mL of pentyl acetate, affording ca. 70 mg of crystalline Letermovir / (S)-(+)-2- Amino- 1 -butanol salt (yield: 25% with respect to the racemate, enantiomeric excess: 84%).

[0544] Example 2.13: Quinine / pentyl acetate (15 hours)

[0545] Experimental procedure: 0.6 g of quinine and 1 g of the racemic 2-{(4R,S)-8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetic acid were dissolved in 3 mL of pentyl acetate at 90 °C. The solution was cooled down to 40 °C, then seeded with R Enantiomer / quinine salt, then stirred for 2 hours and allowed to cool down for 15 hours whilst stirring. The obtained solid was filtered off, washed with pentyl acetate (0.2 mL, twice) and dried under vacuum overnight (3 to 6 mBar, 50 °C). 500 mg of crystalline R-Enantiomer / quinine salt were obtained (yield: 32% with respect to the racemate, enantiomeric excess: 84%).

[0546] Example 2.14: Quinidine / pentyl acetate (15 hours) Experimental procedure: 1.7 g of quinidine and 3 g of the racemic 2-{(4R,S)-8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetic acid were dissolved in 6 mL of pentyl acetate at 85 °C. The solution was cooled down to 40 °C, then seeded with Letermovir / quinidine salt, then stirred for 5 hours and allowed to cool down for 15 hours whilst stirring. The obtained solid was filtered off, washed with pentyl acetate (1 mL, thrice) and dried under vacuum (3 to 6 mBar, 50 °C, 4 hours). 1.10 g of crystalline Letermovir / quinidine salt were obtained (yield: 24% with respect to the racemate, enantiomeric excess: 86%).

[0547] Example 2.15: Enantiomeric resolution of a Racemate Tosylate salt

[0548] Experimental procedure: 0.15 g of the racemic 2-{(4R,S)-8-fhioro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate tosylate salt (characterization is provided in Table 59) and 2.1 eq of (S)-(+)-2- Amino- 1 -butanol (20 mg) were dissolved in 0.5 mL of pentyl acetate at 85 °C. The solution was cooled down to room temperature, then seeded with Letermovir / (S)-(+)-2- Amino-1 -butanol salt, then allowed to cool down for 15 hours whilst stirring. The obtained suspension was filtered off, affording ca. 50 mg crystalline Letermovir / (S)-(+)-2- Amino- 1- butanol salt (yield: 30% with respect to the racemate, enantiomeric excess: 91%).

[0549] Table 59: Characterization of the Racemic Tosylate salt

[0550] Example 2.16: Enantiomeric resolution of a Racemate Calcium salt

[0551] Experimental procedure: 0.15 g of the racemic 2-{(4R,S)-8-fhioro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate calcium salt (characterization is provided in Table 60) and 1.1 eq of (S)-(+)-2- Amino- 1 -butanol (20 mg) were dissolved in 0.5 mL of pentyl acetate at 85 °C. The solution was cooled down to room temperature, then seeded with Letermovir calcium salt, then stirred for 5 hours and allowed to cool down for 15 hours whilst stirring. The solution was allowed to partially evaporate under air, affording ca. 50 mg of crystalline Letermovir of (S)- (+)-2-Amino-l -butanol salt (yield: 30% with respect to the racemate, enantiomeric excess: 92%).

[0552] Table 60: Characterization of the Racemic Calcium salt

[0553] Example 2.17: Enantiomeric resolution of a Racemate Diphenylurea co-crystal

[0554] Experimental procedure: 0.15 g of the racemic 2-{(4R,S)-8-fhroro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetic acid diphenylurea co-crystal (characterization is provided in Table 61) and 1.1 eq of (S)-(+)-2- Amino- 1 -butanol (20 mg) were suspended in 0.5 mL of pentyl acetate at 85 °C. The suspension was cooled down to room temperature, then seeded with Letermovir / (S)-(+)-2- Amino- 1 -butanol salt, then allowed to cool down for 15 hours whilst stirring. The obtained suspension was filtered off, affording ca. 40 mg crystalline Letermovir / (S)-(+)-2-Amino-l -butanol salt mixed with excess diphenyl urea (enantiomeric excess > 99%).

[0555] Table 61: Characterization of the Racemate Diphenylurea co-crystal

[0556] Example 2.18: Esterification of the R-Enantiomer

[0557] Experimental procedure: To a solution of R-Enantiomer (531 mg, 1 eq, 927 pmol) in MeOH (6.72 mL), sulfuric acid (126 mg, 76.9 pL, 96% wt, 1.33 eq, 1.23 mmol) was added. The reaction mixture was stirred at 80 °C for 20 hours. The reaction was cooled down to room temperature and concentrated under vacuo. The resulting residue was dissolved in DCM and extracted with NaHCCh saturated aqueous solution. The aqueous phase was extracted with DCM. The combined organic fractions were dried with ISfeSCU, filtered and concentrated under vacuo to obtain the methyl ester of the R-Enantiomer (602 mg, 1.03 mmol, 111%) as a white solid. Yield higher than 100% due to the presence of solvent (DCM) in the crude.

[0558] Example 2.19: Epimerization of the methyl ester of the R-Enantiomer with tBuOK

[0559] Experimental procedure: The methyl ester of the R-Enantiomer (600 mg, 1 eq, 1.02 mmol) was added in a tube, followed by / BuOK (4.1 eq) and acetonitrile (2.56 mL). The reaction mixture was stirred at 50 °C for 2 hours. Then, water (2.40 g, 2.40 mL, 130 eq, 133 mmol) was added and the reaction was stirred at 50 °C for another 2 hours. The reaction was cooled down, concentrated under vacuo and acidified (pH = 4) with an acetate buffer solution (0.1 M, 70 mL) at pH = 4. The resulting suspension was extracted with DCM (3 x 50 mL) and concentrated under vacuo to obtain a mixture of the R-Enantiomer and Letermovir (470 mg). The mixture was dissolved in acetone (1.2 mL, 390 mg / mL). Then, water (15.6 mL, 26.0 vol.) was added via a syringe pump in 1 hour (0.26 mL / min) with vigorous stirring. The suspension was left stirring at room temperature for 15 hours. The suspension was filtered under vacuo and the flask was washed with water (3.0 mL, thrice). The resulting solid was dried under vacuo to obtain the enantiomeric mixture of R-Enantiomer and Letermovir (421.5 mg, 736.2 pmol, 72.0%) as a white solid. The ee was measured via UPLC and it was determined to be 11.0%, with slight excess of the R-Enantiomer. With the above context, the following consecutively numbered embodiments provide further specific aspects of the invention: 1. A method for producing 2-{(4S)8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2- methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetic acid (“Letermovir”) or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof, comprising the steps: i) providing a mixture comprising Letermovir and 2-{(4R)8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetic acid (“R-Enantiomer”) or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof; ii) contacting said mixture with an enantiomerically enriched compound of Formula (I) wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxyphenyl, benzyl and CH2OH,

[0560] R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4-nitrophenyl, quinolinyl and methoxyquinolinyl

[0561] R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3- C5-cycloalkyl,

[0562] R7 is H or C1-C6-alkyl, wherein R a1nd R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R a1nd R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R a1nd Rs, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3- C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6-alkenyl, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring, thereby producing a Letermovir salt of the compound of Formula (I) and an R-Enantiomer salt of the compound of Formula (I), iii-1) separating the Letermovir salt of the compound of Formula (I); iv-1) converting the Letermovir salt of the compound of Formula (I) into Letermovir or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof; and optionally v-1) isolating Letermovir or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof.

[0563] 2. The method for producing Letermovir according to embodiment 1, wherein said Letermovir is in an amorphous state and wherein said method further comprises precipitation of Letermovir obtained in step iv-1) or v-1) from a solvent selected from the group consisting of acetic acid, formic acid, triethylamine, ethyl acetate, butyl acetate, methyl acetate, isobutyl acetate, propyl acetate, isopropyl acetate, ethyl formate, isopropanol, 1 -propanol, n-pentanol, ethanol, methanol, n-butanol, 2-butanol, 2-methyl-l propanol, 3 -methyl- 1 -butanol, tert-butanol, cyclohexanone, acetone, methyl ethyl ketone, 3 -pentanone, methyl butyl ketone, methyl isobutyl ketone, tetrahydrofuran, 1,2-dimeth oxy ethane, dioxane, 2-ethoxy ethanol, 2- methoxyethanol, ethyleneglycol, formamide, N,N-dimethylacetamide, N,N- dimethylformamide, dimethylsulfoxide, nitromethane, pyridine, sulfolane, tetralin, 1,2- di chloroethane, di chloromethane, 1,1,2-tri chloroethane, 1,1,1 -tri chloroethane, chloroform, chlorobenzene, toluene, cumene, xylenes, anisole, acetonitrile, N-methyl pyrrolidone, dimethyl carbonate, pentyl acetate, or mixtures thereof, by an antisolvent selected from the group consisting of n-heptane, pentane, n-octane, diisopropyl ether, cyclohexane, hexane, methylcyclohexane, tert-butyl methyl ether, ethyl ether, cyclopentyl methyl ether, and water, or mixtures thereof, preferably from a solvent selected from the group consisting of acetone, acetonitrile, ethyl acetate, isobutyl acetate, isopropyl acetate, propyl acetate, butyl acetate, dimethylcarbonate, chlorobenzene, chloroform, 1,2-di chloroethane, di chloromethane, dioxane, ethanol, ethyl formate, isobutanol, isopropanol, methyl acetate, methyl ethyl ketone, methyl isobutyl ketone, methanol, nitromethane, 3 -pentanone, 1 -propanol, tert-butanol, 1,1,1- tri chloroethane, tetrahydrofuran, toluene, 3 -methyl- 1 -butanol, N,N-dimethylformamide and xylenes, or mixtures thereof, by an antisolvent selected from the group consisting of cyclohexane, diisopropyl ether, tert-butyl methyl ether, ethyl ether, water and n-heptane, or mixtures thereof, more preferably from a solvent selected from the group consisting of acetone, acetonitrile, ethyl acetate, isobutyl acetate, isopropyl acetate, propyl acetate, butyl acetate, dimethyl carbonate, chlorobenzene, chloroform, 1,2-di chloroethane, di chloromethane, dioxane, ethanol, ethyl formate, isobutanol, isopropanol, methyl acetate, methyl ethyl ketone, methyl isobutyl ketone, methanol, nitromethane, 3 -pentanone, 1 -propanol, tert-butanol, 1,1,1- trichloroethane, tetrahydrofuran, toluene, and xylenes, or mixtures thereof, and the antisolvent is selected from the group consisting of cyclohexane, diisopropyl ether, water and n-heptane, or mixtures thereof, even more preferably from a solvent selected from the group consisting of acetone, acetonitrile, ethyl acetate, ethanol, isopropanol, methanol, methyl ethyl ketone, tetrahydrofuran, dioxane, toluene, 3 -methyl- 1 -butanol, tert-butanol, N,N-dimethylformamide and di chloromethane or mixtures thereof, by an antisolvent selected from the group consisting of n-heptane, diisopropyl ether, tert-butyl methyl ether, ethyl ether and water, or mixtures thereof, most preferred from a water miscible solvent acetone or acetonitrile into excess stirred water, to obtain amorphous Letermovir, followed by isolation via filtration or centrifugation.

[0564] 3. A method for producing a Letermovir salt of a compound of Formula (I), comprising the steps: i) providing a mixture comprising Letermovir and R-Enantiomer or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof; ii) contacting said mixture with an enantiomerically enriched compound of Formula (I), thereby producing a Letermovir salt of the compound of Formula (I) and an R-Enantiomer salt of the compound of Formula (I); iii-1) separating the Letermovir salt of the compound of Formula (I), wherein the compound of Formula (I) is as defined in embodiment 1.

[0565] 4. A method for enantiomeric separation of a mixture comprising Letermovir and R- Enantiomer, comprising the steps: i) providing a mixture comprising Letermovir and R-Enantiomer or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof; ii) contacting said mixture with an enantiomerically enriched compound of Formula (I), thereby producing a Letermovir salt of the compound of Formula (I) and an R-Enantiomer salt of the compound of Formula (I), iii-1) separating the Letermovir salt of the compound of Formula (I); iv-1) transferring the Letermovir salt of the compound of Formula (I) into the compound of Formula (I) and Letermovir and optionally v-1) isolating Letermovir, wherein the compound of Formula (I) is as defined in embodiment 1.

[0566] 5. The method for enantiomeric separation of a mixture comprising Letermovir and R- Enantiomer according to embodiment 4, further comprising the steps: vi-1) isolating the R-Enantiomer salt of the compound of Formula (I); vii-1) transferring the R-Enantiomer salt of the compound of Formula (I) into the compound of Formula (I) and R-Enantiomer; and optionally viii-1) isolating R-Enantiomer, wherein the compound of Formula (I) is as defined in embodiment 1.

[0567] 6. A method for enantiomeric separation of a mixture comprising Letermovir and R- Enantiomer, comprising the steps: i) providing a mixture comprising Letermovir and R-Enantiomer or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof; ii) contacting said mixture with an enantiomerically enriched compound of Formula (I), thereby producing a Letermovir salt of the compound of Formula (I) and an R-Enantiomer salt of the compound of Formula (I); iii-2) separating the R-Enantiomer salt of the compound of Formula (I); iv-2) transferring the R-Enantiomer salt of the compound of Formula (I) into the compound of Formula (I) and R-Enantiomer; and optionally v-2) isolating R-Enantiomer, wherein the compound of Formula (I) is as defined in embodiment 1.

[0568] 7. The method for enantiomeric separation of a mixture comprising Letermovir and R- Enantiomer according to embodiment 6, further comprising the steps: vi-2) isolating the Letermovir salt of the compound of Formula (I); vii-2) transferring the Letermovir salt of the compound of Formula (I) into the compound of Formula (I) and Letermovir; and optionally viii-2) isolating Letermovir.

[0569] 8. The method according to any of embodiments 4, 5 or 7, wherein said method further comprises precipitation of Letermovir obtained in step iv-1), v-1), vii-2) or viii-2) from a solvent selected from the group consisting of acetic acid, formic acid, tri ethyl amine, ethyl acetate, butyl acetate, methyl acetate, isobutyl acetate, propyl acetate, isopropyl acetate, ethyl formate, isopropanol, 1 -propanol, n-pentanol, ethanol, methanol, n-butanol, 2-butanol, 2- m ethyl- 1 propanol, 3 -methyl- 1 -butanol, Zc / V-butanol, cyclohexanone, acetone, methyl ethyl ketone, 3 -pentanone, methyl butyl ketone, methyl isobutyl ketone, tetrahydrofuran, 1,2- dimethoxyethane, dioxane, 2-ethoxyethanol, 2-methoxyethanol, ethyleneglycol, formamide, N,N-dimethylacetamide, N,N-dimethylformamide, dimethylsulfoxide, nitromethane, pyridine, sulfolane, tetralin, 1,2 -di chloroethane, dichloromethane, 1,1,2-tri chloroethane, 1,1,1- trichloroethane, chloroform, chlorobenzene, toluene, cumene, xylenes, anisole, acetonitrile, N- methyl pyrrolidone, dimethyl carbonate, pentyl acetate, or mixtures thereof, by an antisolvent selected from the group consisting of n-heptane, pentane, n-octane, diisopropyl ether, cyclohexane, hexane, methylcyclohexane, tert-butyl methyl ether, ethyl ether, cyclopentyl methyl ether, and water, or mixtures thereof, preferably from a solvent selected from the group consisting of acetone, acetonitrile, ethyl acetate, isobutyl acetate, isopropyl acetate, propyl acetate, butyl acetate, dimethylcarbonate, chlorobenzene, chloroform, 1,2-di chloroethane, di chloromethane, dioxane, ethanol, ethyl formate, isobutanol, isopropanol, methyl acetate, methyl ethyl ketone, methyl isobutyl ketone, methanol, nitromethane, 3 -pentanone, 1 -propanol, tert-butanol, 1,1,1 -tri chloroethane, tetrahydrofuran, toluene, 3 -methyl- 1 -butanol, N,N- dimethylformamide and xylenes, or mixtures thereof, by an anti solvent selected from the group consisting of cyclohexane, diisopropyl ether, tert-butyl methyl ether, ethyl ether, water and n- heptane, or mixtures thereof, more preferably from a solvent selected from the group consisting of acetone, acetonitrile, ethyl acetate, isobutyl acetate, isopropyl acetate, propyl acetate, butyl acetate, dimethyl carbonate, chlorobenzene, chloroform, 1,2-di chloroethane, di chloromethane, dioxane, ethanol, ethyl formate, isobutanol, isopropanol, methyl acetate, methyl ethyl ketone, methyl isobutyl ketone, methanol, nitromethane, 3 -pentanone, 1 -propanol, tert-butanol, 1,1,1- trichloroethane, tetrahydrofuran, toluene, and xylenes, or mixtures thereof, and the antisolvent is selected from the group consisting of cyclohexane, diisopropyl ether, water and n-heptane, or mixtures thereof, even more preferably from a solvent selected from the group consisting of acetone, acetonitrile, ethyl acetate, ethanol, isopropanol, methanol, methyl ethyl ketone, tetrahydrofuran, dioxane, toluene, 3 -methyl- 1 -butanol, tert-butanol, N,N-dimethylformamide and di chloromethane or mixtures thereof, by an antisolvent selected from the group consisting of n-heptane, diisopropyl ether, tert-butyl methyl ether, ethyl ether and water, or mixtures thereof, most preferred from a water miscible solvent acetone or acetonitrile into excess stirred water, to obtain amorphous Letermovir, followed by isolation via filtration or centrifugation.

[0570] 9. The method according to any of embodiments 1 to 8, wherein step ii) is carried out in a solid state.

[0571] 10. The method according to embodiments 1 to 5, wherein step ii) is carried out in a solid state and separating the Letermovir salt of the compound of Formula (I) in step iii-1) is conducted by means of dissolving the R-Enantiomer salt of the compound of Formula (I) in a solvent selected from the group consisting of ketones, such as acetone, methyl ethyl ketone, cyclohexanone, 4-methylcyclohexanone, 4-methyl-2-pentanone or 3 -pentanone; alkanes, such as pentane, hexane, heptane or isooctane; cycloalkanes, such as cyclohexane or cyclopentane; aromatic solvents, such as chlorobenzene, 1,2-di chlorobenzene, cumene, toluene or xylenes; esters such as ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, ethyl propionate, methyl propionate, isoamyl propionate, isobutyl propionate, hexyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, cyclohexyl butyrate, benzyl butyrate, isobutyl formate, ethyl formate, ethyl formate, isopropyl formate, butyl formate, pentyl formate, diethylene glycol monoethyl ether acetate and ethylene glycol diacetate; ethers, such as diisopropyl ether, cyclopentyl methyl ether, butyl ether, diethoxymethane, anisole, ethylene glycol dimethyl ether, diethylene glycol diethyl ether or dimethoxyethane; alcohols such as ethanol, methanol, 2-butanol, isopropanol, n-butanol, diethylene glycol, isobutanol, isopentanol or tert-butanol; nitriles, such as acetonitrile; and carbonates, such as dimethyl carbonate or diethyl carbonate; or mixtures thereof, preferably selected from the group consisting of acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, isoamyl propionate, isobutyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, isoamyl butyrate, diethylene glycol monoethyl ether acetate, ethylene glycol diacetate, cyclohexyl butyrate, benzyl butyrate, diisopropylether, cyclopentyl methyl ether, cumene, isopropanol, 2- butanol, acetonitrile and dimethylcarbonate or mixtures thereof, and isolating the solid phase comprising the Letermovir salt of the compound of Formula (I).

[0572] 11. The method according to embodiments 1 to 5, wherein step ii) is carried out in a solid state and separating the Letermovir salt of the compound of Formula (I) in step iii-1) is conducted by means of dissolving the Letermovir salt of the compound of Formula (I) in a solvent selected from the group consisting of ketones, such as acetone, methyl ethyl ketone, cyclohexanone, 4- methylcyclohexanone, 4-methyl-2-pentanone or 3 -pentanone; alkanes, such as pentane, hexane, heptane or isooctane; cycloalkanes, such as cyclohexane or cyclopentane; aromatic solvents, such as chlorobenzene, 1,2-di chlorobenzene, cumene, toluene or xylenes; esters such as ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, ethyl propionate, methyl propionate, isoamyl propionate, isobutyl propionate, hexyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, cyclohexyl butyrate, benzyl butyrate, isobutyl formate, ethyl formate, ethyl formate, isopropyl formate, butyl formate, pentyl formate, diethylene glycol monoethyl ether acetate and ethylene glycol diacetate; ethers, such as diisopropyl ether, cyclopentyl methyl ether, butyl ether, diethoxymethane, anisole, ethylene glycol dimethyl ether, diethylene glycol diethyl ether or dimethoxyethane; alcohols such as ethanol, methanol, 2-butanol, isopropanol, n-butanol, diethylene glycol, isobutanol, isopentanol or tert-butanol; nitriles, such as acetonitrile; and carbonates, such as dimethyl carbonate or diethyl carbonate; or mixtures thereof, preferably selected from the group consisting of acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, isoamyl propionate, isobutyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, isoamyl butyrate, diethylene glycol monoethyl ether acetate, ethylene glycol diacetate, cyclohexyl butyrate, benzyl butyrate, diisopropylether, cyclopentyl methyl ether, cumene, isopropanol, 2- butanol, acetonitrile and dimethylcarbonate or mixtures thereof, and isolating the solid phase comprising the R-Enantiomer salt of the compound of Formula (I).

[0573] 12. The method according to any of embodiments 1 to 8, wherein step ii) is carried out in a liquid phase.

[0574] 13. The method according to any of embodiments 1 to 12, wherein the ratio of Letermovir to R-Enantiomer in said mixture in step i) is in the range of from 10:90 to 90: 10, preferably from 20:80 to 80:20, more preferably from 30:70 to 70:30, even more preferably from 40:60 to 60:40, most preferred from 45:55 to 55:45.

[0575] 14. The method according to any of embodiments 1 to 13, wherein said mixture in step i) is racemic 2-{(4R,S)8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-

[0576] (trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetic acid or a salt thereof, or a solvate thereof, or a salt of a solvate thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof.

[0577] 15. The method according to any of embodiments 1 to 8 and 12, wherein step (ii) is carried out in presence of a solvent selected from the group consisting of ketones, such as acetone, methyl ethyl ketone, cyclohexanone, 4-methylcyclohexanone, 4-methyl-2-pentanone or 3 -pentanone; alkanes, such as pentane, hexane, heptane or isooctane; cycloalkanes, such as cyclohexane or cyclopentane; aromatic solvents, such as chlorobenzene, 1,2-di chlorobenzene, cumene, toluene or xylenes; esters such as ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, ethyl propionate, methyl propionate, isoamyl propionate, isobutyl propionate, hexyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, cyclohexyl butyrate, benzyl butyrate, isobutyl formate, ethyl formate, ethyl formate, isopropyl formate, butyl formate, pentyl formate, diethylene glycol monoethyl ether acetate and ethylene glycol diacetate; ethers, such as diisopropyl ether, cyclopentyl methyl ether, butyl ether, diethoxymethane, anisole, ethylene glycol dimethyl ether, diethylene glycol diethyl ether or dimethoxyethane; alcohols such as ethanol, methanol, 2-butanol, isopropanol, n-butanol, diethylene glycol, isobutanol, isopentanol or tert-butanol; nitriles, such as acetonitrile; and carbonates, such as dimethyl carbonate or diethyl carbonate; or mixtures thereof, preferably selected from the group consisting of acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, isoamyl propionate, isobutyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, isoamyl butyrate, diethylene glycol monoethyl ether acetate, ethylene glycol diacetate, cyclohexyl butyrate, benzyl butyrate, diisopropylether, cyclopentyl methyl ether, cumene, isopropanol, 2-butanol, acetonitrile and dimethylcarbonate or mixtures thereof.

[0578] 16. The method according to any of embodiments 1 to 15, wherein the enantiomeric purity of said compound of Formula (I) is at least 80% ee, preferably et least 85% ee, more preferably at least 90% ee, more preferably at least 95% ee, more preferably at least 98% ee, most preferred at least 99% ee.

[0579] 17. The method according to any of embodiments 1 to 5, wherein the compound of Formula (I) is a compound of formula (II) or (III) wherein

[0580] R3 is selected from the group consisting of H, C1-C3-alkyl and phenyl,

[0581] R7 is H or C1-C3-alkyl, R8 is selected from the group consisting of H, OH, methyl or ethyl, wherein R7 and R8, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein step iii-1) comprises isolating the solid phase comprising the Letermovir salt of the compound of Formula (II) or (III).

[0582] 18. The method according to any of embodiments 1 to 5, wherein the compound of Formula (I) is a compound of formula (IV) or (V)

[0583] (IV) (V) wherein

[0584] R3 is selected from the group consisting of H, C1-C3-alkyl and phenyl,

[0585] R7 is H or C1-C3-alkyl, R8 is selected from the group consisting of H, OH, methyl or ethyl, wherein R7 and R8, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein step iii-1) comprises isolating the liquid phase comprising the Letermovir salt of the compound of Formula (IV) or (V).

[0586] 19. The method according to embodiment 6 or 7, wherein the compound of Formula (I) is a compound of formula (IV) or (V)

[0587] (IV) (V) wherein

[0588] Rs is selected from the group consisting of H, C1-C3-alkyl and phenyl,

[0589] R7 is H or C1-C3-alkyl, R8 is selected from the group consisting of H, OH, methyl or ethyl, wherein R7 and R8, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein step iii-2) comprises isolating the solid phase comprising the R-Enantiomer salt of the compound of Formula (IV) or (V).

[0590] 20. The method according to embodiment 6 or 7, wherein the compound of Formula (I) is a compound of formula (II) or (III) wherein

[0591] R3 is selected from the group consisting of H, C1-C3-alkyl and phenyl,

[0592] R7 is H or C1-C3-alkyl, R8 is selected from the group consisting of H, OH, methyl or ethyl, wherein R7 and R8, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein step iii-2) comprises isolating the liquid phase comprising the R-Enantiomer salt of the compound of Formula (II) or (III).

[0593] 21. The method according to any of embodiments 1 to 16, wherein the compound of Formula (I) is a compound of formula (VI) or (VII)

[0594] (VI) (VII) wherein R1 is selected from the group consisting of H, C1-C3-alkyl and CH2OH,

[0595] R3 is selected from the group consisting of H, C1-C3-alkyl, phenyl and 4-nitrophenyl,

[0596] R5 and R6 each is independently selected from the group consisting of H and C1-C3-alkyl,

[0597] R7 is H or C1-C3-alkyl, wherein R a1nd R7, together with the atoms to which they are attached, are optionally connected to form a C3-C7-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein R a1nd R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3- C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6-alkenyl, such as 5-ethenyl-l- azabicyclo[2.2.2]octan-2-yl.

[0598] 22. The method according to embodiment 21, wherein R5 and R6 each is H.

[0599] 23. The method according to embodiment 21, wherein the compound of Formula (I) is selected from the group consisting of (S)-(+)-2- Amino- 1 -butanol, (2R)-3-amino-2-methoxy- propan-l-ol, (R)-2-Methoxypropan-l -amine, (S)-(+)-2 -Amino- 1 -hexanol, (S)-(+)-2-Amino-l- pentanol, (R)-(-)-2- Amino- 1 -butanol, L-Phenylalaninol, (lS,2S)-2-Amino-l-(4-nitrophenyl)- 1,3 -propanediol, (R)-(-)-2-Phenylglycinol, (R)-(Tetrahydrofuran-2-yl)methanamine and (lS,2S)-2-amino-l-phenylpropane-l,3-diol, preferably (S)-(+)-2- Amino- 1 -butanol, (2R)-3- amino-2-m ethoxy-propan- 1 -ol, (R)-2-Methoxypropan- 1 -amine, (S)-(+)-2-Amino- 1 -hexanol, (S)-(+)-2-Amino-l -pentanol, (lS,2S)-2-amino-l-phenylpropane-l,3-diol, (R)-[(2S,4S,5R)-5- ethenyl-l-azabicyclo[2.2.2]octan-2-yl](6-methoxyqinolin-4-yl)methanol (quinine) and (S)- [(2R,4S,5R)-5-ethenyl-l-azabicyclo[2.2.2]octan-2-yl](6-methoxyqinolin-4-yl)methanol (quinidine). 24. The method according to embodiment 21, wherein the compound of Formula (I) is selected

[0600] 25. The method according to embodiment 23, wherein the compound of Formula (I) is (S)- (+)-2- Amino- 1 -butanol and the solvent is pentyl acetate.

[0601] 26. The method according to any of embodiments 1 to 25, wherein said mixture in step i) is the mixture comprising Letermovir and R-Enantiomer, in particular the racemate, which is provided in step i) by means of the following steps: a) reacting R-Enantiomer with a C1-C2-alcohol in the presence of an acid to obtain an ester of R-Enantiomer, and b) treating the ester of R-Enantiomer obtained in step a) with a base to obtain a mixture comprising Letermovir and R-Enantiomer.

[0602] 27. Use of a compound of Formula (I) for producing Letermovir, wherein the compound of Formula (I) is defined as in embodiment 1. 28. Use of a compound of Formula (I) for enantiomeric separation of a mixture comprising Letermovir and R-Enantiomer, wherein the compound of Formula (I) is defined as in embodiment 4.

[0603] 29. An R-Enantiomer salt of a compound of Formula (I) wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxyphenyl, benzyl and CH2OH,

[0604] R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4-nitrophenyl, quinolinyl and methoxyquinolinyl

[0605] R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3- C5-cycloalkyl,

[0606] R7 is H or C1-C6-alkyl, wherein R a1nd R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R a1nd R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R a1nd R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3- C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6-alkenyl, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring. 30. The R-Enantiomer salt of a compound of Formula (I) according to embodiment 29, wherein the compound of Formula (I) is a compound of Formula (VI) or (VII) wherein R1 is selected from the group consisting of H, C1-C3-alkyl and CH2OH,

[0607] R3 is selected from the group consisting of H, C1-C3-alkyl, phenyl and 4-nitrophenyl,

[0608] R5 and R6 each is independently selected from the group consisting of H and C1-C3-alkyl,

[0609] R7 is H or C1-C3-alkyl, wherein R a1nd R7, together with the atoms to which they are attached, are optionally connected to form a C3-C7-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein R a1nd R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3- C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6-alkenyl, such as such as 5-ethenyl-l- azabicyclo[2.2.2]octan-2-yl.

[0610] 31. A Letermovir salt of a compound of Formula (I), wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxyphenyl, benzyl and CH2OH, R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4-nitrophenyl, quinolinyl and methoxyquinolinyl

[0611] R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3- C5-cycloalkyl,

[0612] R7 is H or C1-C6-alkyl, wherein R a1nd R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R a1nd R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R a1nd R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3- C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6-alkenyl, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring.

[0613] 32. The Letermovir salt of a compound of Formula (I) according to embodiment 31, wherein the compound of Formula (I) is a compound of Formula (VI) or (VII)

[0614] (VI) (VII) wherein R1 is selected from the group consisting of H, C1-C3-alkyl and CH2OH,

[0615] R3 is selected from the group consisting of H, C1-C3-alkyl, phenyl and 4-nitrophenyl,

[0616] R5 and R6 each is independently selected from the group consisting of H and C1-C3-alkyl,

[0617] R7 is H or C1-C3-alkyl, wherein R a1nd R7, together with the atoms to which they are attached, are optionally connected to form a C3-C7-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein R a1nd R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3- C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6-alkenyl, such as such as 5-ethenyl-l- azabicyclo[2.2.2]octan-2-yl.

[0618] 33. The Letermovir salt of a compound of Formula (I) according to embodiment 32, wherein said salt is selected from the group consisting of (R)-l-hydroxybutan-2-aminium salt of 2- {(4S)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-

[0619] (trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetate (1 : 1), (S)- 1 -hydroxy-3 - phenylpropan-2-aminium salt of 2-{(4S)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3- [2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetate (1 : 1), (1S,2S)- l,3-dihydroxy-l-(4-nitrophenyl)propan-2-aminium salt of 2-{(4S)-8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 :1) , (R)-2-hydroxy-l-phenylethan-l-aminium salt of 2- {(4S)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5- (trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetate (1 : 1), (S)-l-hydroxybutan-2- aminium salt of 2-{(4S)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5- (trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetate (1 : 1), (S)-l-hydroxyhexan-2- aminium salt of 2-{(4S)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5- (trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetate (1 : 1), (S)-l -hydroxypentan -2- aminium salt of 2-{(4S)8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5- (trifhroromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetate (1 : 1), (lS,2S)-l,3-dihydroxy-l- phenylpropan-2-aminium salt of 2-{(4S)8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2- methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetate (1 : 1), (R)-2- methoxypropan-l-aminium salt of 2-{(4S)8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3- [2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetate (1 : 1), (R)-

[0620] (tetrahydrofuran-2-yl)methanaminium salt of 2-{(4S)8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 : 1) and (S)-[(2R,4S,5R)-5-ethenyl-l- azabicyclo[2.2.2]octan-2-yl](6-methoxyqinolin-4-yl)methanol (quinidine) salt of 2-{(4S)8- fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1:1).

[0621] 34. The Letermovir salt of a compound of Formula (I) according to embodiment 32, wherein said salt is selected from the group consisting of

[0622]

[0623] 35. The Letermovir salt of a compound of Formula (I) according to embodiment 32, wherein said salt is (R)-l-hydroxybutan-2-aminium salt of 2-{(4S)-8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 :1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 6.1, 8.9, 12.3, 15.3, 16.8, 17.9, 20.6, 21.4 and 22.4 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°.

[0624] 36. The Letermovir salt of a compound of Formula (I) according to embodiment 32, wherein said salt is (S)-l -hydroxy-3 -phenylpropan-2-aminium salt of 2-{(4S)-8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 :1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 5.4, 5.8, 14.3, 14.8, 15.2, 17.8, 18.4, 19.1, 19.5, 19.9, 21.4, 21.8 and 22.2 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°. 37. The Letermovir salt of a compound of Formula (I) according to embodiment 32, wherein said salt is (lS,2S)-l,3-dihydroxy-l-(4-nitrophenyl)propan-2-aminium salt of 2-{(4S)-8- fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 :1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 5.8, 8.9, 11.7, 14.4, 17.5, 19.2, 19.8, 20.8 and 21.2 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°.

[0625] 38. The Letermovir salt of a compound of Formula (I) according to embodiment 32, wherein said salt is (R)-2-hydroxy-l-phenylethan-l-aminium salt of 2-{(4S)-8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 :1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 5.6, 5.9, 11.8, 14.5, 15.4, 16.9, 17.5, 18.2, 19.4, 20.5, 21.1 and 21.6 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°.

[0626] 39. The Letermovir salt of a compound of Formula (I) according to embodiment 32, wherein said salt is (S)-l-hydroxybutan-2-aminium salt of 2-{(4S)-8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 :1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 6.1, 8.9, 12.3, 15.2, 17.6, 17.9, 20.6 and 22.3 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°.

[0627] 40. The Letermovir salt of a compound of Formula (I) according to embodiment 32, wherein said salt is (S)-l-hydroxyhexan-2-aminium salt of 2-{(4S)-8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 :1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 6.2, 9.9, 12.4, 13.2, 14.6, 16.6, 18.2, 18.8, 19.8, 20.3, 22.6 and 23.9 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°.

[0628] 41. The Letermovir salt of a compound of Formula (I) according to embodiment 32, wherein said salt is (S)-l-hydroxypentan-2-aminium salt of 2-{(4S)8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 :1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 6.3, 9.9, 12.7, 13.3, 14.8, 16.5,

[0629] 18.4, 18.8, 20.5, 23.0 and 24.2 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°.

[0630] 42. The Letermovir salt of a compound of Formula (I) according to embodiment 32, wherein said salt is (lS,2S)-l,3-dihydroxy-l-phenylpropan-2-aminium salt of 2-{(4S)8-fhroro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 :1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 5.7, 5.8, 9.3, 11.7, 14.5, 15.3, 18.6,

[0631] 19.4, 20.6 and 21.1 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°.

[0632] 43. The Letermovir salt of a compound of Formula (I) according to embodiment 32, wherein said salt is (R)-2-methoxypropan-l-aminium salt of 2-{(4S)8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 :1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 6.0, 9.3, 12.0, 15.2, 17.5, 18.8,

[0633] 20.4, 21.7 and 25.9 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°.

[0634] 44. The Letermovir salt of a compound of Formula (I) according to embodiment 32, wherein said salt (R)-(tetrahydrofuran-2-yl)methanaminium salt of 2-{(4S)8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 :1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 6.0, 9.3, 12.0, 15.2, 17.5, 18.7, 20.4 and 21.8 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°.

[0635] 45. The R-Enantiomer salt of a compound of Formula (I) according to embodiment 30, wherein said salt is (R)-l-hydroxy-2-methoxypropan-3-aminium salt of 2-{(4R)8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 :1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 6.0, 9.2, 12.0, 15.2, 17.5, 18.6,

[0636] 20.4, 21.3, 21.8 and 26.0 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°. 46. The Letermovir salt of a compound of Formula (I) according to embodiment 32, wherein said salt is (S)-[(2R,4S,5R)-5-ethenyl-l-azabicyclo[2.2.2]octan-2-yl](6-methoxyqinolin-4- yl)methanol (quinidine) salt of 2-{(4S)8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2- methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetate (1 : 1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 4.2, 9.4, 13.4, 14.2, 14.4, 16.5, 16.7, 17.4, 17.7, 18.3, 18.5, 18.8, 19.6, 22.2 and 23.9 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°.

[0637] 47. The R-Enantiomer salt of a compound of Formula (I) according to embodiment 30, wherein said salt is (R)-[(2S,4S,5R)-5-ethenyl-l-azabicyclo[2.2.2]octan-2-yl](6-methoxyqinolin-4- yl)methanol (quinine) salt of 2-{(4R)8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2- methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetate (1 : 1) and said salt is characterized by having an X-ray diffraction pattern which comprises 2-theta angle values of: 5.1, 9.9, 13.3, 13.5, 15.4, 15.7, 16.0, 16.8, 17.2, 18.0, 18.7, 19.1, 20.4, 21.4 and 22.6 degrees, and said 2-theta angle values have a normal deviation of ± 0.1°.

Claims

CLAIMS1. A method for producing 2-{(4S)8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2- methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetic acid (“Letermovir”) or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof, comprising the steps: i) providing a mixture comprising Letermovir and 2-{(4R)8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetic acid (“R-Enantiomer”) or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof; ii) contacting said mixture with an enantiomerically enriched compound of Formula (I)wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxyphenyl, benzyl and CH2OH,R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4-nitrophenyl, quinolinyl and methoxyquinolinyl,R5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3- C5-cycloalkyl,R7 is H or C1-C6-alkyl, wherein R a1nd R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring,wherein R1 and R7 together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7 together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R a1nd R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3- C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6-alkenyl, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring, thereby producing a Letermovir salt of the compound of Formula (I) and an R-Enantiomer salt of the compound of Formula (I), iii-1) separating the Letermovir salt of the compound of Formula (I); iv-1) converting the Letermovir salt of the compound of Formula (I) into Letermovir or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof; and optionally v-1) isolating Letermovir or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof.

2. The method for producing Letermovir according to claim 1, wherein said Letermovir is in an amorphous state and wherein said method further comprises precipitation of Letermovir obtained in step iv-1) or v-1) from a solvent selected from the group consisting of acetic acid, formic acid, triethylamine, ethyl acetate, butyl acetate, methyl acetate, isobutyl acetate, propyl acetate, isopropyl acetate, ethyl formate, isopropanol, 1 -propanol, n-pentanol, ethanol, methanol, n-butanol, 2-butanol, 2 -m ethyl- 1 propanol, 3 -methyl- 1 -butanol, tert-butanol, cyclohexanone, acetone, methyl ethyl ketone, 3 -pentanone, methyl butyl ketone, methyl isobutyl ketone, tetrahydrofuran, 1,2-dimeth oxy ethane, dioxane, 2-ethoxy ethanol, 2- methoxyethanol, ethyleneglycol, formamide, N,N-dimethylacetamide, N,N- dimethylformamide, dimethylsulfoxide, nitromethane, pyridine, sulfolane, tetralin, 1,2- di chloroethane, di chloromethane, 1,1,2-tri chloroethane, 1,1,1 -tri chloroethane, chloroform,chlorobenzene, toluene, cumene, xylenes, anisole, acetonitrile, N-methyl pyrrolidone, dimethyl carbonate, pentyl acetate, or mixtures thereof, by an antisolvent selected from the group consisting of n-heptane, pentane, n-octane, diisopropyl ether, cyclohexane, hexane, methylcyclohexane, tert-butyl methyl ether, ethyl ether, cyclopentyl methyl ether, and water, or mixtures thereof, preferably from a solvent selected from the group consisting of acetone, acetonitrile, ethyl acetate, isobutyl acetate, isopropyl acetate, propyl acetate, butyl acetate, dimethylcarbonate, chlorobenzene, chloroform, 1,2-di chloroethane, di chloromethane, dioxane, ethanol, ethyl formate, isobutanol, isopropanol, methyl acetate, methyl ethyl ketone, methyl isobutyl ketone, methanol, nitromethane, 3-pentanone, 1-propanol, tert-butanol, 1,1,1- tri chloroethane, tetrahydrofuran, toluene, 3 -methyl- 1 -butanol, N,N-dimethylformamide and xylenes, or mixtures thereof, by an antisolvent selected from the group cyclohexane, diisopropyl ether, tert-butyl methyl ether, ethyl ether, pentane, n-octane, water and n-heptane, or mixtures thereof, more preferably from a solvent selected from the group consisting of acetone, acetonitrile, ethyl acetate, ethanol, isopropanol, methanol, methyl ethyl ketone, tetrahydrofuran, dioxane, toluene, 3 -methyl- 1 -butanol, tert-butanol, N,N-dimethylformamide and di chloromethane or mixtures thereof, by an antisolvent selected from the group consisting of n-heptane, diisopropyl ether, tert-butyl methyl ether, ethyl ether and water, or mixtures thereof, even more preferably from a water miscible solvent acetone or acetonitrile into excess stirred water, to obtain amorphous Letermovir, followed by isolation via filtration or centrifugation.

3. A method for producing a Letermovir salt of a compound of Formula (I), comprising the steps: i) providing a mixture comprising Letermovir and R-Enantiomer or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof; ii) contacting said mixture with an enantiomerically enriched compound of Formula (I), thereby producing a Letermovir salt of the compound of Formula (I) and an R-Enantiomer salt of the compound of Formula (I); iii-1) separating the Letermovir salt of the compound of Formula (I), wherein the compound of Formula (I) is as defined in claim 1.

4. A method for enantiomeric separation of a mixture comprising Letermovir and R- Enantiomer, comprising the steps: i) providing a mixture comprising Letermovir and R-Enantiomer or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof; ii) contacting said mixture with an enantiomerically enriched compound of Formula (I), thereby producing a Letermovir salt of the compound of Formula (I) and an R-Enantiomer salt of the compound of Formula (I), iii-1) separating the Letermovir salt of the compound of Formula (I); iv-1) transferring the Letermovir salt of the compound of Formula (I) into the compound of Formula (I) and Letermovir and optionally v-1) isolating Letermovir, wherein the compound of Formula (I) is as defined in claim 1.

5. The method for enantiomeric separation of a mixture comprising Letermovir and R- Enantiomer according to claim 4, further comprising the steps: vi-1) isolating the R-Enantiomer salt of the compound of Formula (I); vii-1) transferring the R-Enantiomer salt of the compound of Formula (I) into the compound of Formula (I) and R-Enantiomer; and optionally viii-1) isolating R-Enantiomer, wherein the compound of Formula (I) is as defined in claim 1.

6. A method for enantiomeric separation of a mixture comprising Letermovir and R- Enantiomer, comprising the steps:i) providing a mixture comprising Letermovir and R-Enantiomer or a salt thereof or a solvate thereof or a solvate of a salt thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof; ii) contacting said mixture with an enantiomerically enriched compound of Formula (I), thereby producing a Letermovir salt of the compound of Formula (I) and an R-Enantiomer salt of the compound of Formula (I); iii-2) separating the R-Enantiomer salt of the compound of Formula (I); iv-2) transferring the R-Enantiomer salt of the compound of Formula (I) into the compound of Formula (I) and R-Enantiomer; and optionally v-2) isolating R-Enantiomer, wherein the compound of Formula (I) is as defined in claim 1.

7. The method for enantiomeric separation of a mixture comprising Letermovir and R- Enantiomer according to claim 6, further comprising the steps: vi-2) isolating the Letermovir salt of the compound of Formula (I); vii-2) transferring the Letermovir salt of the compound of Formula (I) into the compound of Formula (I) and Letermovir; and optionally viii-2) isolating Letermovir.

8. The method according to any of claims 4, 5 or 7, wherein said method further comprises precipitation of Letermovir obtained in step iv-1), v-1), vii-2) or viii-2) from a solvent selected from the group consisting of acetic acid, formic acid, triethylamine, ethyl acetate, butyl acetate, methyl acetate, isobutyl acetate, propyl acetate, isopropyl acetate, ethyl formate, isopropanol,1 -propanol, n-pentanol, ethanol, methanol, n-butanol, 2-butanol, 2 -m ethyl- 1 propanol, 3- m ethyl- 1 -butanol, tert-butanol, cyclohexanone, acetone, methyl ethyl ketone, 3 -pentanone, methyl butyl ketone, methyl isobutyl ketone, tetrahydrofuran, 1,2-dimethoxy ethane, dioxane,2-ethoxyethanol, 2-methoxyethanol, ethyleneglycol, formamide, N,N-dimethylacetamide, N,N-dimethylformamide, dimethylsulfoxide, nitromethane, pyridine, sulfolane, tetralin, 1,2-di chloroethane, di chloromethane, 1,1,2-tri chloroethane, 1,1,1 -tri chloroethane, chloroform, chlorobenzene, toluene, cumene, xylenes, anisole, acetonitrile, N-methyl pyrrolidone, dimethyl carbonate, pentyl acetate, or mixtures thereof, by an antisolvent selected from the group consisting of n-heptane, pentane, n-octane, diisopropyl ether, cyclohexane, hexane, methylcyclohexane, tert-butyl methyl ether, ethyl ether, cyclopentyl methyl ether, and water, or mixtures thereof, preferably from a solvent selected from the group consisting of acetone, acetonitrile, ethyl acetate, isobutyl acetate, isopropyl acetate, propyl acetate, butyl acetate, dimethylcarbonate, chlorobenzene, chloroform, 1,2-di chloroethane, di chloromethane, dioxane, ethanol, ethyl formate, isobutanol, isopropanol, methyl acetate, methyl ethyl ketone, methyl isobutyl ketone, methanol, nitromethane, 3-pentanone, 1-propanol, tert-butanol, 1,1,1- tri chloroethane, tetrahydrofuran, toluene, 3 -methyl- 1 -butanol, N,N-dimethylformamide and xylenes, or mixtures thereof, by an antisolvent selected from the group consisting of cyclohexane, diisopropyl ether, tert-butyl methyl ether, ethyl ether, pentane, n-octane, water and n-heptane, or mixtures thereof, more preferably from a solvent selected from the group consisting of acetone, acetonitrile, ethyl acetate, ethanol, isopropanol, methanol, methyl ethyl ketone, tetrahydrofuran, dioxane, toluene, 3 -methyl- 1 -butanol, tert-butanol, N,N- dimethylformamide and dichloromethane or mixtures thereof, by an antisolvent selected from the group consisting of n-heptane, diisopropyl ether, tert-butyl methyl ether, ethyl ether and water, or mixtures thereof, even more preferably from a water miscible solvent acetone or acetonitrile into excess stirred water, to obtain amorphous Letermovir, followed by isolation via filtration or centrifugation.

9. The method according to any of claims 1 to 8, wherein step ii) is carried out in a solid state.

10. The method according to claims 1 to 5, wherein step ii) is carried out in a solid state and separating the Letermovir salt of the compound of Formula (I) in step iii-1) is conducted by means of dissolving the R-Enantiomer salt of the compound of Formula (I) in a solvent selected from the group consisting of ketones, such as acetone, methyl ethyl ketone, cyclohexanone, 4- methylcyclohexanone, 4-methyl-2-pentanone or 3-pentanone; alkanes, such as pentane, hexane, heptane or isooctane; cycloalkanes, such as cyclohexane or cyclopentane; aromatic solvents, such as chlorobenzene, 1,2-di chlorobenzene, cumene, toluene or xylenes; esters such as ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, ethyl propionate, methyl propionate, isoamyl propionate, isobutyl propionate, hexyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate,cyclohexyl butyrate, benzyl butyrate, isobutyl formate, ethyl formate, ethyl formate, isopropyl formate, butyl formate, pentyl formate, diethylene glycol monoethyl ether acetate and ethylene glycol diacetate; ethers, such as diisopropyl ether, cyclopentyl methyl ether, butyl ether, diethoxymethane, anisole, ethylene glycol dimethyl ether, diethylene glycol diethyl ether or dimethoxyethane; alcohols such as ethanol, methanol, 2-butanol, isopropanol, n-butanol, diethylene glycol, isobutanol, isopentanol or tert-butanol; nitriles, such as acetonitrile; and carbonates, such as dimethyl carbonate or diethyl carbonate; or mixtures thereof, preferably selected from the group consisting of acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, isoamyl propionate, isobutyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, isoamyl butyrate, diethylene glycol monoethyl ether acetate, ethylene glycol diacetate, cyclohexyl butyrate, benzyl butyrate, diisopropylether, cyclopentyl methyl ether, cumene, isopropanol, 2- butanol, acetonitrile and dimethylcarbonate or mixtures thereof, and isolating the solid phase comprising the Letermovir salt of the compound of Formula (I).

11. The method according to claims 1 to 5, wherein step ii) is carried out in a solid state and separating the Letermovir salt of the compound of Formula (I) in step iii-1) is conducted by means of dissolving the Letermovir salt of the compound of Formula (I) in a solvent selected from the group consisting of ketones, such as acetone, methyl ethyl ketone, cyclohexanone, 4- methylcyclohexanone, 4-methyl-2-pentanone or 3 -pentanone; alkanes, such as pentane, hexane, heptane or isooctane; cycloalkanes, such as cyclohexane or cyclopentane; aromatic solvents, such as chlorobenzene, 1,2-di chlorobenzene, cumene, toluene or xylenes; esters such as ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, ethyl propionate, methyl propionate, isoamyl propionate, isobutyl propionate, hexyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, cyclohexyl butyrate, benzyl butyrate, isobutyl formate, ethyl formate, ethyl formate, isopropyl formate, butyl formate, pentyl formate, diethylene glycol monoethyl ether acetate and ethylene glycol diacetate; ethers, such as diisopropyl ether, cyclopentyl methyl ether, butyl ether, diethoxymethane, anisole, ethylene glycol dimethyl ether, diethylene glycol diethyl ether or dimethoxyethane; alcohols such as ethanol, methanol, 2-butanol, isopropanol, n-butanol, diethylene glycol, isobutanol, isopentanol or tert-butanol; nitriles, such as acetonitrile; and carbonates, such as dimethyl carbonate or diethyl carbonate; or mixtures thereof, preferably selected from the group consisting of acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, isoamylpropionate, isobutyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, isoamyl butyrate, diethylene glycol monoethyl ether acetate, ethylene glycol diacetate, cyclohexyl butyrate, benzyl butyrate, diisopropylether, cyclopentyl methyl ether, cumene, isopropanol, 2- butanol, acetonitrile and dimethylcarbonate or mixtures thereof, and isolating the solid phase comprising the R-Enantiomer salt of the compound of Formula (I).

12. The method according to any of claims 1 to 8, wherein step ii) is carried out in a liquid phase.

13. The method according to any of claims 1 to 12, wherein the ratio of Letermovir to R- Enantiomer in said mixture in step i) is in the range of from 10:90 to 90: 10, preferably from 20:80 to 80:20, more preferably from 30:70 to 70:30, even more preferably from 40:60 to 60:40, most preferred from 45:55 to 55:45.

14. The method according to any of claims 1 to 13, wherein said mixture of step i) is racemic 2-{(4R,S)8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetic acid or a salt thereof, or a solvate thereof, or a salt of a solvate thereof or a co-crystal thereof or a solvate of a co-crystal thereof or a salt of a co-crystal thereof or a solvate of a salt of a co-crystal thereof.

15. The method according to any of claims 1 to 8 and 12, wherein step (ii) is carried out in presence of a solvent selected from the group consisting of ketones, such as acetone, methyl ethyl ketone, cyclohexanone, 4-methylcyclohexanone, 4-methyl-2-pentanone or 3 -pentanone; alkanes, such as pentane, hexane, heptane or isooctane; cycloalkanes, such as cyclohexane or cyclopentane; aromatic solvents, such as chlorobenzene, 1,2-di chlorobenzene, cumene, toluene or xylenes; esters such as ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, ethyl propionate, methyl propionate, isoamyl propionate, isobutyl propionate, hexyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, cyclohexyl butyrate, benzyl butyrate, isobutyl formate, ethyl formate, ethyl formate, isopropyl formate, butyl formate, pentyl formate, diethylene glycol monoethyl ether acetate and ethylene glycol diacetate; ethers, such as diisopropyl ether, cyclopentyl methyl ether, butyl ether, diethoxymethane, anisole, ethylene glycol dimethyl ether, diethylene glycol diethyl ether or dimethoxyethane; alcohols such as ethanol, methanol, 2-butanol, isopropanol, n-butanol, diethylene glycol, isobutanol, isopentanol or tert-butanol; nitriles, such asacetonitrile; and carbonates, such as dimethyl carbonate or diethyl carbonate; or mixtures thereof, preferably selected from the group consisting of acetonitrile, ethyl acetate, methyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, methyl propionate, isoamyl propionate, isobutyl propionate, ethyl butyrate, propyl butyrate, amyl butyrate, isoamyl butyrate, diethylene glycol monoethyl ether acetate, ethylene glycol diacetate, cyclohexyl butyrate, benzyl butyrate, diisopropylether, cyclopentyl methyl ether, cumene, isopropanol, 2-butanol, acetonitrile and dimethylcarbonate or mixtures thereof.

16. The method according to any of claims 1 to 15, wherein the enantiomeric purity of said compound of Formula (I) is at least 80% ee, preferably et least 85% ee, more preferably at least 90% ee, more preferably at least 95% ee, more preferably at least 98% ee, most preferred at least 99% ee.

17. The method according to any of claims 1 to 5, wherein the compound of Formula (I) is a compound of formula (II) or (III)whereinR3 is selected from the group consisting of H, C1-C3-alkyl and phenyl,R7 is H or C1-C3-alkyl, R8 is selected from the group consisting of H, OH, methyl or ethyl, wherein R7 and R8, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein step iii-1) comprises isolating the solid phase comprising the Letermovir salt of the compound of Formula (II) or (III).

18. The method according to any of claims 1 to 5, wherein the compound of Formula (I) is a compound of formula (IV) or (V)(IV) (V) whereinR3 is selected from the group consisting of H, C1-C3-alkyl and phenyl,R7 is H or C1-C3-alkyl, R8 is selected from the group consisting of H, OH, methyl or ethyl, wherein R7 and R8, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein step iii-1) comprises isolating the liquid phase comprising the Letermovir salt of the compound of Formula (IV) or (V).

19. The method according to any of claims 6 or 7, wherein the compound of Formula (I) is a compound of formula (IV) or (V)(IV) (V) whereinR3 is selected from the group consisting of H, C1-C3-alkyl and phenyl,R7 is H or C1-C3-alkyl, R8 is selected from the group consisting of H, OH, methyl or ethyl,wherein R7 and R8, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein step iii-2) comprises isolating the solid phase comprising the R-Enantiomer salt of the compound of Formula (IV) or (V).

20. The method according to claims 6 or 7, wherein the compound of Formula (I) is a compound of formula (II) or (III)whereinR3 is selected from the group consisting of H, C1-C3-alkyl and phenyl,R7 is H or C1-C3-alkyl, R8 is selected from the group consisting of H, OH, methyl or ethyl, wherein R7 and R8, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein step iii-2) comprises isolating the liquid phase comprising the R-Enantiomer salt of the compound of Formula (II) or (III).

21. The method according to any of claims 1 to 16, wherein the compound of Formula (I) is a compound of formula (VI) or (VII)(VI) (VII) wherein R1 is selected from the group consisting of H, C1-C3-alkyl and CH2OH,R3 is selected from the group consisting of H, C1-C3-alkyl, phenyl and 4-nitrophenyl,R5 and R6 each is independently selected from the group consisting of H and C1-C3-alkyl,R7 is H or C1-C3-alkyl, wherein R a1nd R7, together with the atoms to which they are attached, are optionally connected to form a C3-C7-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein R a1nd R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3- C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6-alkenyl.

22. The method according to claim 21, wherein R5 and R6 each is H.

23. The method according to claim 21 , wherein the compound of Formula (I) is selected from the group consisting of (S)-(+)-2-Amino-l -butanol, (2R)-3-amino-2-methoxy-propan-l-ol, (R)-2 -Methoxypropan- 1 -amine, (S)-(+)-2- Amino- 1 -hexanol, (S)-(+)-2- Amino- 1 -pentanol, (R)-(-)-2-Amino- 1 -butanol, L-Phenylalaninol, ( 1 S,2S)-2- Amino- 1 -(4-nitrophenyl)- 1,3- propanediol, (R)-(-)-2-Phenylglycinol, (R)-(Tetrahydrofuran-2-yl)methanamine, (lS,2S)-2- amino-l-phenylpropane-l,3-diol, (R)-[(2S,4S,5R)-5-ethenyl-l-azabicyclo[2.2.2]octan-2-yl](6- methoxyqinolin-4-yl)methanol (quinine) and (S)-[(2R,4S,5R)-5-ethenyl-l- azabicyclo[2.2.2]octan-2-yl](6-methoxyqinolin-4-yl)methanol (quinidine).

24. The method according to claim 21, wherein the compound of Formula (I) is selected from25. The method according to claim 23, wherein the compound of Formula (I) is (S)-(+)-2- Amino-1 -butanol and the solvent is pentyl acetate.

26. The method according to any of claims 1 to 25, wherein said mixture in step i) is the mixture comprising Letermovir and R-Enantiomer, in particular the racemate, which is provided in step i) by means of the following steps: a) reacting R-Enantiomer with a C1-C2-alcohol in the presence of an acid to obtain an ester of R-Enantiomer, and b) treating the ester of R-Enantiomer obtained in step a) with a base to obtain a mixture comprising Letermovir and R-Enantiomer.

27. Use of a compound of Formula (I) for producing Letermovir, wherein the compound of Formula (I) is defined as in claim 1.

28. Use of a compound of Formula (I) for enantiomeric separation of a mixture comprising Letermovir and R-Enantiomer, wherein the compound of Formula (I) is defined as in claim 4.

29. An R-Enantiomer salt of a compound of Formula (I)wherein R1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxyphenyl, benzyl and CH2OH,R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4-nitrophenyl, quinolinyl and methoxyquinolinylR5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3- C5-cycloalkyl,R7 is H or C1-C6-alkyl, wherein R a1nd R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R a1nd R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R a1nd R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3- C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6-alkenyl, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring.

30. The R-Enantiomer salt of a compound of Formula (I) according to claim 29, wherein the compound of Formula (I) is a compound of Formula (VI) or (VII)(VI) (VII) wherein R1 is selected from the group consisting of H, C1-C3-alkyl and CH2OH,R3 is selected from the group consisting of H, C1-C3-alkyl, phenyl and 4-nitrophenyl,R5 and R6 each is independently selected from the group consisting of H and C1-C3-alkyl,R7 is H or C1-C3-alkyl, wherein R a1nd R7, together with the atoms to which they are attached, are optionally connected to form a C3-C7-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein R a1nd R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3- C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6-alkenyl.

31. A Letermovir salt of a compound of Formula (I),whereinR1 and R2 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, methoxyphenyl, benzyl and CH2OH,R3 and R4 each is independently selected from the group consisting of H, C1-C6-alkyl, phenyl, benzyl, 4-nitrophenyl, quinolinyl and methoxyquinolinylR5 and R6 each is independently selected from the group consisting of H, C1-C6-alkyl and C3- C5-cycloalkyl,R7 is H or C1-C6-alkyl, wherein R a1nd R3, together with the atoms to which they are attached, are optionally connected to form a C3-C6-carbocyclic ring, wherein R a1nd R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, wherein R a1nd R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3- C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6-alkenyl, wherein R5 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring.

32. The Letermovir salt of a compound of Formula (I) according to claim 31, wherein the compound of Formula (I) is a compound of Formula (VI) or (VII)(VI) (VII) wherein R1 is selected from the group consisting of H, C1-C3-alkyl and CH2OH,R3 is selected from the group consisting of H, C1-C3-alkyl, phenyl and 4-nitrophenyl,R5 and R6 each is independently selected from the group consisting of H and C1-C3-alkyl,R7 is H or C1-C3-alkyl,wherein R a1nd R7, together with the atoms to which they are attached, are optionally connected to form a Cs-Cv-oxocyclic ring, wherein R3 and R7, together with the atoms to which they are attached, are optionally connected to form a C3-C6-oxocyclic ring, and wherein R a1nd R5, together with the atoms to which they are attached, are optionally connected to form a C3-C6-heterocyclic ring or to form a C5-C8-heterobicyclic system, wherein said C3- C6-heterocyclic ring or said C5-C8-heterobicyclic system is optionally substituted with 1, 2 or 3 groups independently selected from C1-C6-alkyl or C1-C6-alkenyl.

33. The Letermovir salt of a compound of Formula (I) according to claim 32, wherein said salt is selected from the group consisting of (R)-l-hydroxybutan-2-aminium salt of 2-{(4S)-8- fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 :1), (S)-l -hydroxy-3 -phenylpropan-2-aminium salt of 2- {(4S)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifhroromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetate (1 : 1), (lS,2S)-l,3-dihydroxy-l- (4-nitrophenyl)propan-2-aminium salt of 2-{(4S)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetate (1 : 1), (R)-2-hydroxy-l-phenylethan-l-aminium salt of 2-{(4S)-8-fluoro-2-[4-(3- methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 : 1), (S)-l-hydroxybutan-2-aminium salt of2-{(4S)-8-fluoro- 2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 :1), (S)-l-hydroxyhexan-2-aminium salt of 2-{(4S)-8- fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 :1), (S)-l-hydroxypentan-2-aminium salt of 2-{(4S)8- fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4- dihydroquinazolin-4-yl} acetate (1 : 1), (lS,2S)-l,3-dihydroxy-l-phenylpropan-2-aminium salt of 2-{(4S)8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetate (1 : 1), (R)-2-methoxypropan-l- aminium salt of 2-{(4S)8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5- (trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetate (1 : 1), (R)-(tetrahydrofuran-2- yl)methanaminium salt of 2-{(4S)8-fhroro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2- methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetate (1 : 1) and (S)- [(2R,4S,5R)-5-ethenyl-l-azabicyclo[2.2.2]octan-2-yl](6-methoxyqinolin-4-yl)methanol(quinidine) salt of 2-{(4S)8-fluoro-2-[4-(3-methoxyphenyl)piperazin-l-yl]-3-[2-methoxy-5- (trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl} acetate (1 : 1).

34. The Letermovir salt of a compound of Formula (I) according to claim 32, wherein said salt is selected from the group consisting of

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