1: 2-((4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-benzo-[f][1,2,4]triazolo[4,3-a][1,4]diazepin-4-yl)acetic acid With N-ethyl-N,N-diisopropylamine; HATU in tetrahydrofuran T=20°C; 3 h; 2: ethylamine in tetrahydrofuran 48 h;

DIEA; HBTU in tetrahydrofuran; 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran; acetonitrile

1.1: triethylamine / dichloromethane / 24 h / Reflux 2.1: acetic acid / 1,2-dichloro-ethane / 2 h / 60 °C 3.1: tetraphosphorus decasulfide; sodium carbonate / 1,2-dichloro-ethane / 2 h / 70 °C 4.1: hydrazine hydrate / tetrahydrofuran / 4 h / 0 - 15 °C 5.1: triethylamine / tetrahydrofuran / 1 h / 20 °C 6.1: acetic acid / tetrahydrofuran / 48 h / 20 °C 7.1: sodium hydroxide / tetrahydrofuran / 5 h / 20 °C 8.1: N-ethyl-N,N-diisopropylamine; HATU / tetrahydrofuran / 3 h / 20 °C 8.2: 48 h View Scheme

1.1: tetraphosphorus decasulfide; sodium carbonate / 1,2-dichloro-ethane / 2 h / 70 °C 2.1: hydrazine hydrate / tetrahydrofuran / 4 h / 0 - 15 °C 3.1: triethylamine / tetrahydrofuran / 1 h / 20 °C 4.1: acetic acid / tetrahydrofuran / 48 h / 20 °C 5.1: sodium hydroxide / tetrahydrofuran / 5 h / 20 °C 6.1: N-ethyl-N,N-diisopropylamine; HATU / tetrahydrofuran / 3 h / 20 °C 6.2: 48 h View Scheme

1.1: hydrazine hydrate / tetrahydrofuran / 4 h / 0 - 15 °C 2.1: triethylamine / tetrahydrofuran / 1 h / 20 °C 3.1: acetic acid / tetrahydrofuran / 48 h / 20 °C 4.1: sodium hydroxide / tetrahydrofuran / 5 h / 20 °C 5.1: N-ethyl-N,N-diisopropylamine; HATU / tetrahydrofuran / 3 h / 20 °C 5.2: 48 h View Scheme

1.1: toluene; diethyl ether / 1 h / 0 - 20 °C 1.2: 2 h / Reflux 2.1: chloroform / 1.5 h / 60 °C 3.1: triethylamine / dichloromethane / 24 h / Reflux 4.1: acetic acid / 1,2-dichloro-ethane / 2 h / 60 °C 5.1: tetraphosphorus decasulfide; sodium carbonate / 1,2-dichloro-ethane / 2 h / 70 °C 6.1: hydrazine hydrate / tetrahydrofuran / 4 h / 0 - 15 °C 7.1: triethylamine / tetrahydrofuran / 1 h / 20 °C 8.1: acetic acid / tetrahydrofuran / 48 h / 20 °C 9.1: sodium hydroxide / tetrahydrofuran / 5 h / 20 °C 10.1: N-ethyl-N,N-diisopropylamine; HATU / tetrahydrofuran / 3 h / 20 °C 10.2: 48 h View Scheme

1.1: 2.25 h / Reflux 2.1: toluene; diethyl ether / 1 h / 0 - 20 °C 2.2: 2 h / Reflux 3.1: chloroform / 1.5 h / 60 °C 4.1: triethylamine / dichloromethane / 24 h / Reflux 5.1: acetic acid / 1,2-dichloro-ethane / 2 h / 60 °C 6.1: tetraphosphorus decasulfide; sodium carbonate / 1,2-dichloro-ethane / 2 h / 70 °C 7.1: hydrazine hydrate / tetrahydrofuran / 4 h / 0 - 15 °C 8.1: triethylamine / tetrahydrofuran / 1 h / 20 °C 9.1: acetic acid / tetrahydrofuran / 48 h / 20 °C 10.1: sodium hydroxide / tetrahydrofuran / 5 h / 20 °C 11.1: N-ethyl-N,N-diisopropylamine; HATU / tetrahydrofuran / 3 h / 20 °C 11.2: 48 h View Scheme

1.1: toluene; diethyl ether / 1 h / 0 - 20 °C 1.2: 2 h / Reflux 2.1: chloroform / 1.5 h / 60 °C 3.1: triethylamine / dichloromethane / 24 h / Reflux 4.1: acetic acid / 1,2-dichloro-ethane / 2 h / 60 °C 5.1: tetraphosphorus decasulfide; sodium carbonate / 1,2-dichloro-ethane / 2 h / 70 °C 6.1: hydrazine hydrate / tetrahydrofuran / 4 h / 0 - 15 °C 7.1: triethylamine / tetrahydrofuran / 1 h / 20 °C 8.1: acetic acid / tetrahydrofuran / 48 h / 20 °C 9.1: sodium hydroxide / tetrahydrofuran / 5 h / 20 °C 10.1: N-ethyl-N,N-diisopropylamine; HATU / tetrahydrofuran / 3 h / 20 °C 10.2: 48 h View Scheme

1.1: chloroform / 1.5 h / 60 °C 2.1: triethylamine / dichloromethane / 24 h / Reflux 3.1: acetic acid / 1,2-dichloro-ethane / 2 h / 60 °C 4.1: tetraphosphorus decasulfide; sodium carbonate / 1,2-dichloro-ethane / 2 h / 70 °C 5.1: hydrazine hydrate / tetrahydrofuran / 4 h / 0 - 15 °C 6.1: triethylamine / tetrahydrofuran / 1 h / 20 °C 7.1: acetic acid / tetrahydrofuran / 48 h / 20 °C 8.1: sodium hydroxide / tetrahydrofuran / 5 h / 20 °C 9.1: N-ethyl-N,N-diisopropylamine; HATU / tetrahydrofuran / 3 h / 20 °C 9.2: 48 h View Scheme

1.1: sodium hydroxide / tetrahydrofuran / 5 h / 20 °C 2.1: N-ethyl-N,N-diisopropylamine; HATU / tetrahydrofuran / 3 h / 20 °C 2.2: 48 h View Scheme