US RE49,698 E1
Substituted dihydroquinazolines
Tobias Wunberg, Solingen (DE); Judith Baumeister, Wuppertal (DE); Ulrich Betz, Wuppertal (DE); Mario Jeske, Wuppertal (DE); Thomas Lampe, Dusseldorf (DE); Susanne Nikolic, Monheim (DE); Jurgen Reefschlager, Oldenburg (DE); Rudolf Schohe-Loop, Wuppertal (DE); Frank Sussmeier, Wuppertal (DE); Holger Zimmermann, Wuppertal (DE); Rolf Grosser, Leverkusen (DE); Kerstin Henninger, Wuppertal (DE); Guy Hewlett, Wuppertal (DE); Jorg Keldenich, Wuppertal (DE); Dieter Lang, Velbert (DE); and Peter Nell, Wuppertal (DE)
Assigned to AIC246 AG & Co. KG, Wuppertal (DE)
Filed by AiCuris Anti-infective Cures GmbH, Wuppertal (DE)
Filed on Jul. 21, 2020, as Appl. No. 16/934,363.
Application 10/832,109 is a continuation of application No. 15/955,254, filed on Apr. 17, 2018, abandoned.
Application 15/955,254 is a continuation of application No. 14/682,512, filed on Apr. 9, 2015, granted, now RE46791, issued on Apr. 17, 2018.
Application 16/934,363 is a reissue of application No. 10/832,109, filed on Apr. 26, 2004, granted, now 7,196,086, issued on Mar. 27, 2007.
Application 14/682,512 is a reissue of application No. 10/832,109, filed on Apr. 26, 2004, granted, now 7,196,086, issued on Mar. 27, 2007.
Claims priority of application No. 10319612 (DE), filed on Feb. 5, 2003.
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 239/84 (2006.01); A61P 31/22 (2006.01); A61P 31/12 (2006.01); A61P 31/00 (2006.01)
CPC C07D 239/84 (2013.01) [A61P 31/00 (2018.01); A61P 31/12 (2018.01); A61P 31/22 (2018.01)] 8 Claims
 
[ 20. A process for preparing a compound of formula (I) or a salt, solvate, or solvate of a salt thereof

OG Complex Work Unit Chemistry
in which
Ar represents aryl which may be substituted by 1 to 3 substituents, where the substituents are selected independently of one another from the group consisting of alkyl, alkoxy, formyl, carboxyl, alkylcarbonyl, alkoxycarbonyl, trifluoromethyl, halogen, cyano, hydroxyl, amino, alkylamino, aminocarbonyl and nitro, where alkyl may be substituted by 1 to 3 substituents,
where the substituents are selected independently of one another from the group consisting of halogen, amino, alkylamino, hydroxyl and aryl,
R1 represents hydrogen, amino, alkyl, alkoxy, alkylamino, alkylthio, cyano, halogen, nitro or trifluoromethyl,
R2 represents hydrogen, alkyl, alkoxy, alkylthio, cyano, halogen, nitro or trifluoromethyl,
R3 represents amino, alkyl, alkoxy, alkylamino, alkylthio, cyano, halogen, nitro, trifluoromethyl, alkylsulphonyl or alkylaminosulphonyl,
R4 represents hydrogen or alkyl,
R5 represents hydrogen or alkyl
or
the radicals R4 and R5 are attached to carbon atoms directly opposing each other in the piperazine ring and form a methylene bridge which is optionally substituted by 1 or 2 methyl groups,
R6 represents alkyl, alkoxy, alkylthio, formyl, carboxyl, aminocarbonyl, alkylcarbonyl, alkoxycarbonyl, trifluoromethyl, halogen, cyano, hydroxyl or nitro,
R7 represents hydrogen, alkyl, alkoxy, alkylthio, formyl, carboxyl, alkylcarbonyl, alkoxycarbonyl, trifluoromethyl, halogen, cyano, hydroxyl or nitro, and
R8 represents hydrogen, alkyl, alkoxy, alkylthio, formyl, carboxyl, alkylcarbonyl, alkoxycarbonyl, trifluoromethyl, halogen, cyano, hydroxyl or nitro,
said process comprising:
(a) reacting a compound of formula (III)

OG Complex Work Unit Chemistry
wherein R6, R7, and R8 are as defined above and R9 is methyl or ethyl, in a two-step reaction initially with a compound of formula (IV)

OG Complex Work Unit Chemistry
in which R1, R2 and R3 are as defined above, and then with a compound of formula (V)

OG Complex Work Unit Chemistry
in which Ar, R4 and R5 are as defined above,
to obtain a compound of formula II

OG Complex Work Unit Chemistry
in which
Ar, R1, R2, R3, R4, R5, R6, R7 and R8 are as defined above, and
R9 is methyl or ethyl; and
(b) reacting the compound of formula (II) with a base in an inert solvent wherein the base is an alkali metal hydroxide or alkali metal carbonate, and the inert solvent is an ether or alcohol.]