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CAS No.: | 1310726-60-3 |
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Name: | Upadacitinib |
Article Data: | 10 |
Molecular Structure: | |
Formula: | C17H19F3N6O |
Molecular Weight: | 380.373 |
Synonyms: | Upadacitinib;ABT-494 |
EINECS: | -0 |
Density: | 1.56±0.1 g/cm3(Predicted) |
PSA: | 78.32000 |
LogP: | 3.23670 |
(3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide
Conditions | Yield |
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With butan-1-ol at 85 - 90℃; | 95% |
trifluoroethylamine
(3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide
Conditions | Yield |
---|---|
Stage #1: (3S,4R)-benzyl-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)pyrrolidine-1-carboxylate With 2,6-dichloropyridine; trifluoromethylsulfonic anhydride In dichloromethane at 0 - 20℃; Inert atmosphere; Stage #2: trifluoroethylamine In dichloromethane at 20℃; Inert atmosphere; | 88% |
trifluoroethylamine
1,1'-carbonyldiimidazole
(3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide
Conditions | Yield |
---|---|
Stage #1: trifluoroethylamine; 1,1'-carbonyldiimidazole In tetrahydrofuran at 30℃; for 1.33333h; Stage #2: 8-((3R,4S)-4-ethylpyrrolidin-3-yl)-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazine bishydrochloride With dipotassium hydrogenphosphate; potassium hydroxide In tetrahydrofuran; water at 25℃; for 1h; pH=9; Concentration; | 87% |
trifluoromethylethylamine
(3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide
Conditions | Yield |
---|---|
Stage #1: trifluoromethylethylamine With triethylamine; 1,1'-carbonyldiimidazole In dichloromethane at 20℃; for 0.5h; Stage #2: 8-((3R,4S)-4-ethylpyrrolidin-3-yl)-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazine In dichloromethane for 6h; | 71% |
(3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide
Conditions | Yield |
---|---|
Multi-step reaction with 4 steps 1.1: lithium tert-butoxide / N,N-dimethyl acetamide / 0.5 h / -10 - 5 °C 1.2: 1 h / -10 °C 2.1: pyridine; trifluoroacetic anhydride / acetonitrile / 2 h / 75 °C 3.1: 10% palladium hydroxide on charcoal; hydrogen / ethanol / 16 h / 50 °C / 1794.37 Torr 3.2: 1 h 4.1: tetrahydrofuran / 1.33 h / 30 °C 4.2: 1 h / 25 °C / pH 9 View Scheme | |
Multi-step reaction with 5 steps 1: lithium tert-butoxide / N,N-dimethyl acetamide 2: pyridine; trifluoroacetic anhydride / acetonitrile / 75 °C 3: sodium hydroxide / 2-methyltetrahydrofuran / 55 °C 4: hydrogen; 10 wt% Pd(OH)2 on carbon 5: dipotassium hydrogenphosphate; potassium hydroxide / tetrahydrofuran View Scheme |
(3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide
Conditions | Yield |
---|---|
Multi-step reaction with 5 steps 1.1: hydrogen bromide; acetic acid / tetrahydrofuran / 5 h / 40 °C 2.1: lithium tert-butoxide / N,N-dimethyl acetamide / 0.5 h / -10 - 5 °C 2.2: 1 h / -10 °C 3.1: pyridine; trifluoroacetic anhydride / acetonitrile / 2 h / 75 °C 4.1: 10% palladium hydroxide on charcoal; hydrogen / ethanol / 16 h / 50 °C / 1794.37 Torr 4.2: 1 h 5.1: tetrahydrofuran / 1.33 h / 30 °C 5.2: 1 h / 25 °C / pH 9 View Scheme | |
Multi-step reaction with 6 steps 1: lithium bromide; toluene-4-sulfonic acid 2: lithium tert-butoxide / N,N-dimethyl acetamide 3: pyridine; trifluoroacetic anhydride / acetonitrile / 75 °C 4: sodium hydroxide / 2-methyltetrahydrofuran / 55 °C 5: hydrogen; 10 wt% Pd(OH)2 on carbon 6: dipotassium hydrogenphosphate; potassium hydroxide / tetrahydrofuran View Scheme | |
Multi-step reaction with 7 steps 1: lithium bromide; toluene-4-sulfonic acid 2: sodium hydride / N,N-dimethyl-formamide 3: trifluoroacetic acid / dichloromethane 4: Lawessons reagent / 1,4-dioxane / 50 °C 5: sodium hydroxide / 2-methyltetrahydrofuran / 55 °C 6: hydrogen; 10 wt% Pd(OH)2 on carbon 7: dipotassium hydrogenphosphate; potassium hydroxide / tetrahydrofuran View Scheme |
(3R,4S)-benzyl 3-(2-bromoacetyl)-4-ethylpyrrolidine-1-carboxylate
(3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide
Conditions | Yield |
---|---|
Multi-step reaction with 4 steps 1.1: lithium tert-butoxide / N,N-dimethyl acetamide / 0.5 h / -10 - 5 °C 1.2: 1 h / -10 °C 2.1: pyridine; trifluoroacetic anhydride / acetonitrile / 2 h / 75 °C 3.1: 10% palladium hydroxide on charcoal; hydrogen / ethanol / 16 h / 50 °C / 1794.37 Torr 3.2: 1 h 4.1: tetrahydrofuran / 1.33 h / 30 °C 4.2: 1 h / 25 °C / pH 9 View Scheme | |
Multi-step reaction with 5 steps 1: lithium tert-butoxide / N,N-dimethyl acetamide 2: pyridine; trifluoroacetic anhydride / acetonitrile / 75 °C 3: sodium hydroxide / 2-methyltetrahydrofuran / 55 °C 4: hydrogen; 10 wt% Pd(OH)2 on carbon 5: dipotassium hydrogenphosphate; potassium hydroxide / tetrahydrofuran View Scheme | |
Multi-step reaction with 6 steps 1: sodium hydride / N,N-dimethyl-formamide 2: trifluoroacetic acid / dichloromethane 3: Lawessons reagent / 1,4-dioxane / 50 °C 4: sodium hydroxide / 2-methyltetrahydrofuran / 55 °C 5: hydrogen; 10 wt% Pd(OH)2 on carbon 6: dipotassium hydrogenphosphate; potassium hydroxide / tetrahydrofuran View Scheme |
(3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide
Conditions | Yield |
---|---|
Multi-step reaction with 3 steps 1.1: pyridine; trifluoroacetic anhydride / acetonitrile / 2 h / 75 °C 2.1: 10% palladium hydroxide on charcoal; hydrogen / ethanol / 16 h / 50 °C / 1794.37 Torr 2.2: 1 h 3.1: tetrahydrofuran / 1.33 h / 30 °C 3.2: 1 h / 25 °C / pH 9 View Scheme |
2-bromo-5-(p-toluenesulfonyl)-5H-pyrrolo[2,3-b]pyrazine
(3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide
Conditions | Yield |
---|---|
Multi-step reaction with 5 steps 1.1: potassium carbonate; palladium diacetate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene / toluene / 95 °C 1.2: 2 h 2.1: lithium tert-butoxide / N,N-dimethyl acetamide / 0.5 h / -10 - 5 °C 2.2: 1 h / -10 °C 3.1: pyridine; trifluoroacetic anhydride / acetonitrile / 2 h / 75 °C 4.1: 10% palladium hydroxide on charcoal; hydrogen / ethanol / 16 h / 50 °C / 1794.37 Torr 4.2: 1 h 5.1: tetrahydrofuran / 1.33 h / 30 °C 5.2: 1 h / 25 °C / pH 9 View Scheme | |
Multi-step reaction with 6 steps 1: potassium carbonate; palladium diacetate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene / toluene / 95 °C 2: lithium tert-butoxide / N,N-dimethyl acetamide 3: pyridine; trifluoroacetic anhydride / acetonitrile / 75 °C 4: sodium hydroxide / 2-methyltetrahydrofuran / 55 °C 5: hydrogen; 10 wt% Pd(OH)2 on carbon 6: dipotassium hydrogenphosphate; potassium hydroxide / tetrahydrofuran View Scheme | |
Multi-step reaction with 7 steps 1: tris-(dibenzylideneacetone)dipalladium(0); tert-butyl XPhos; sodium t-butanolate / 1,4-dioxane / 90 °C 2: sodium hydride / N,N-dimethyl-formamide 3: hydrogenchloride / 1,4-dioxane 4: Lawessons reagent / 1,4-dioxane / 50 °C 5: hydrogen bromide; acetic acid 6: triethylamine / N,N-dimethyl-formamide / 55 °C 7: sodium hydroxide / 1,4-dioxane View Scheme |
(3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide
Conditions | Yield |
---|---|
Multi-step reaction with 6 steps 1.1: phosphoric acid / tert-butyl methyl ether / 0.5 h 1.2: 1.5 h / 20 °C 1.3: 2.25 h / -5 - -1 °C / Reflux 2.1: hydrogen bromide; acetic acid / tetrahydrofuran / 5 h / 40 °C 3.1: lithium tert-butoxide / N,N-dimethyl acetamide / 0.5 h / -10 - 5 °C 3.2: 1 h / -10 °C 4.1: pyridine; trifluoroacetic anhydride / acetonitrile / 2 h / 75 °C 5.1: 10% palladium hydroxide on charcoal; hydrogen / ethanol / 16 h / 50 °C / 1794.37 Torr 5.2: 1 h 6.1: tetrahydrofuran / 1.33 h / 30 °C 6.2: 1 h / 25 °C / pH 9 View Scheme | |
Multi-step reaction with 7 steps 1: 1,1'-carbonyldiimidazole 2: lithium bromide; toluene-4-sulfonic acid 3: lithium tert-butoxide / N,N-dimethyl acetamide 4: pyridine; trifluoroacetic anhydride / acetonitrile / 75 °C 5: sodium hydroxide / 2-methyltetrahydrofuran / 55 °C 6: hydrogen; 10 wt% Pd(OH)2 on carbon 7: dipotassium hydrogenphosphate; potassium hydroxide / tetrahydrofuran View Scheme | |
Multi-step reaction with 7 steps 1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane 2: acetonitrile; tetrahydrofuran / 0 °C 3: lithium tert-butoxide / N,N-dimethyl acetamide 4: pyridine; trifluoroacetic anhydride / acetonitrile / 75 °C 5: sodium hydroxide / 2-methyltetrahydrofuran / 55 °C 6: hydrogen; 10 wt% Pd(OH)2 on carbon 7: dipotassium hydrogenphosphate; potassium hydroxide / tetrahydrofuran View Scheme |