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CAS No.: | 1025967-78-5 |
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Name: | lifitegrast |
Article Data: | 14 |
Molecular Structure: | |
Formula: | C29H24Cl2N2O7S |
Molecular Weight: | 615.491 |
Synonyms: | lifitegrast;Lifitegrast, SAR 1118;L-Phenylalanine,N-[[2-(6-benzofuranylcarbonyl)-5,7-dichloro-1,2,3,4-tetrahydro-6-isoquinolinyl]carbonyl]-3-(methylsulfonyl)-;N-[[2-(6-Benzofuranylcarbonyl)-5,7-dichloro-1,2,3,4-tetrahydro-6-isoquinolinyl]carbonyl]-3-(methylsulfonyl)-L-phenylalanine;SAR 1118;(S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid;(S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic |
EINECS: | -0 |
Density: | 1.479±0.06 g/cm3(Predicted) |
Boiling Point: | 811.9±65.0 °C(Predicted) |
PSA: | 142.37000 |
LogP: | 6.17690 |
(S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid
Conditions | Yield |
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With phosphoric acid In dichloromethane; water at 50℃; for 0.5h; | 96% |
((S)-benzyl 2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-methylsulfonyl)phenyl)propanoate
(S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid
Conditions | Yield |
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With formic acid; palladium 10% on activated carbon; triethylamine In tetrahydrofuran; methanol at 20℃; for 4h; | 95% |
With formic acid; palladium 10% on activated carbon; triethylamine In tetrahydrofuran; methanol Reagent/catalyst; Solvent; | n/a |
With lithium hydroxide monohydrate In water; acetone at -5 - 0℃; for 1h; Reagent/catalyst; Solvent; Temperature; | |
With hydrogenchloride In water; acetonitrile at 3 - 25℃; for 19.5h; Solvent; Temperature; Reagent/catalyst; Inert atmosphere; | 3.8 g |
(S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid
Conditions | Yield |
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Stage #1: 2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3 ,4-tetrahydroisoquinoline-6-carboxylic acid With [2-(1H-indol-3-yl)-ethyl]-methylamine; N-ethyl-N,N-diisopropylamine; HATU In tetrahydrofuran at 40℃; for 2h; Inert atmosphere; Stage #2: (S)-2-amino-3-(3-(methylsulfonyl)phenyl)propanoic acid In tetrahydrofuran at 20 - 30℃; | 92% |
Stage #1: 2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3 ,4-tetrahydroisoquinoline-6-carboxylic acid With triethylamine In N,N-dimethyl-formamide at 28℃; for 0.166667h; Stage #2: With N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 5 - 8℃; for 2h; Stage #3: (S)-2-amino-3-(3-(methylsulfonyl)phenyl)propanoic acid In N,N-dimethyl-formamide at 8℃; for 1h; |
(S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid
Conditions | Yield |
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Stage #1: (S)-2-amino-3-(3-(methylsulfonyl)phenyl)propanoic acid; 3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl 2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxylate With N-ethyl-N,N-diisopropylamine In acetonitrile at 40 - 45℃; Stage #2: With hydrogenchloride In water at 0 - 5℃; for 1h; pH=5; | 87% |
With N-ethyl-N,N-diisopropylamine In water; acetonitrile at 20 - 45℃; for 4h; |
benzofuran-6-carboxylic acid
(S)-2-(5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid
(S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid
Conditions | Yield |
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With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at -10 - 20℃; Reagent/catalyst; Solvent; Temperature; | 83.8% |
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 10 - 20℃; for 1.5h; |
(S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid
Conditions | Yield |
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With water; lithium hydroxide In methanol at 25 - 30℃; for 3h; Reagent/catalyst; Solvent; | 80% |
(S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid
Conditions | Yield |
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Stage #1: (S)-2-amino-3-(3-(methylsulphonyl)phenyl)propanoic acid hydrochloride With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; Inert atmosphere; Stage #2: C19H12Cl3NO3 In dichloromethane at 0 - 5℃; Temperature; Inert atmosphere; | 77% |
(2S)-3-(3-bromophenyl)-2-[(tert-butoxycarbonyl)amino]propanoic acid
(S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid
Conditions | Yield |
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Multi-step reaction with 7 steps 1: copper(l) iodide; caesium carbonate; L-proline / dimethyl sulfoxide / 9 h / 100 °C 2: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 20 °C 3: hydrogenchloride / 1,4-dioxane; dichloromethane; water / 0 °C 4: triethylamine; HATU / N,N-dimethyl-formamide / 18 h / 20 °C 5: hydrogenchloride / 1,4-dioxane; water / 2 h / 20 °C 6: N-ethyl-N,N-diisopropylamine / dichloromethane / 1 h / 0 °C 7: palladium 10% on activated carbon; formic acid; triethylamine / tetrahydrofuran; methanol / 4 h / 20 °C View Scheme | |
Multi-step reaction with 7 steps 1.1: copper(l) iodide; caesium carbonate; L-proline; sodium methansulfinate / dimethyl sulfoxide / 9 h / 95 - 100 °C 2.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap 3.1: hydrogenchloride / dichloromethane; 1,4-dioxane / 0 °C 4.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide / 0.17 h 4.2: 18 h / 20 °C 5.1: hydrogenchloride / 1,4-dioxane / 2 h / 20 °C 6.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.5 h / 0 - 5 °C 7.1: triethylamine; palladium 10% on activated carbon; formic acid / tetrahydrofuran; methanol View Scheme | |
Multi-step reaction with 7 steps 1: copper(l) iodide; caesium carbonate; L-proline; sodium methansulfinate / dimethyl sulfoxide / 9 h / 95 - 100 °C 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap 3: hydrogenchloride / dichloromethane; 1,4-dioxane / 0 °C 4: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide 5: hydrogenchloride / water; 1,4-dioxane 6: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.5 h / 0 - 5 °C 7: triethylamine; palladium 10% on activated carbon; formic acid / tetrahydrofuran; methanol View Scheme |
(S)-2-((tert-butoxycarbonyl)amino)-3-((3-methylsulfonyl)phenyl)propanol
(S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid
Conditions | Yield |
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Multi-step reaction with 6 steps 1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 20 °C 2: hydrogenchloride / 1,4-dioxane; dichloromethane; water / 0 °C 3: triethylamine; HATU / N,N-dimethyl-formamide / 18 h / 20 °C 4: hydrogenchloride / 1,4-dioxane; water / 2 h / 20 °C 5: N-ethyl-N,N-diisopropylamine / dichloromethane / 1 h / 0 °C 6: palladium 10% on activated carbon; formic acid; triethylamine / tetrahydrofuran; methanol / 4 h / 20 °C View Scheme | |
Multi-step reaction with 6 steps 1.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap 2.1: hydrogenchloride / dichloromethane; 1,4-dioxane / 0 °C 3.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide / 0.17 h 3.2: 18 h / 20 °C 4.1: hydrogenchloride / 1,4-dioxane / 2 h / 20 °C 5.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.5 h / 0 - 5 °C 6.1: triethylamine; palladium 10% on activated carbon; formic acid / tetrahydrofuran; methanol View Scheme | |
Multi-step reaction with 6 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap 2: hydrogenchloride / dichloromethane; 1,4-dioxane / 0 °C 3: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide 4: hydrogenchloride / water; 1,4-dioxane 5: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.5 h / 0 - 5 °C 6: triethylamine; palladium 10% on activated carbon; formic acid / tetrahydrofuran; methanol View Scheme | |
Multi-step reaction with 6 steps 1.1: O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / dichloromethane / 0.25 h / 25 - 35 °C 1.2: 5 h / 25 - 45 °C 2.1: hydrogenchloride / 1,4-dioxane; dichloromethane / 2 h / 25 - 35 °C 3.1: triethylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 0.25 h / 25 - 35 °C 3.2: 5 h / 25 - 45 °C 4.1: hydrogenchloride / 1,4-dioxane; dichloromethane / 25 - 35 °C 5.1: triethylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 0.25 h / 25 - 35 °C 5.2: 5 h / 25 - 45 °C 6.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 25 - 35 °C View Scheme |
(S)-benzyl 2-((tert-butoxycarbonyl)amino)-3-((3-methylsulfonyl)phenyl)propionate
(S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid
Conditions | Yield |
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Multi-step reaction with 5 steps 1: hydrogenchloride / 1,4-dioxane; dichloromethane; water / 0 °C 2: triethylamine; HATU / N,N-dimethyl-formamide / 18 h / 20 °C 3: hydrogenchloride / 1,4-dioxane; water / 2 h / 20 °C 4: N-ethyl-N,N-diisopropylamine / dichloromethane / 1 h / 0 °C 5: palladium 10% on activated carbon; formic acid; triethylamine / tetrahydrofuran; methanol / 4 h / 20 °C View Scheme | |
Multi-step reaction with 5 steps 1.1: hydrogenchloride / dichloromethane; 1,4-dioxane / 0 °C 2.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide / 0.17 h 2.2: 18 h / 20 °C 3.1: hydrogenchloride / 1,4-dioxane / 2 h / 20 °C 4.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.5 h / 0 - 5 °C 5.1: triethylamine; palladium 10% on activated carbon; formic acid / tetrahydrofuran; methanol View Scheme | |
Multi-step reaction with 5 steps 1: hydrogenchloride / dichloromethane; 1,4-dioxane / 0 °C 2: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide 3: hydrogenchloride / water; 1,4-dioxane 4: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.5 h / 0 - 5 °C 5: triethylamine; palladium 10% on activated carbon; formic acid / tetrahydrofuran; methanol View Scheme |