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Chemical Structure| 2374782-04-2 Chemical Structure| 2374782-04-2
Chemical Structure| 2374782-04-2

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FAPI-46 is a quinoline-based radioactive tracer targeting fibroblast activation protein (FAP), demonstrating high tumor uptake and prolonged accumulation time, making it suitable for tumor imaging studies in various cancers.

4.5 *For Research Use Only! Not for Human Use. We Do Not Sell to Patients.

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Product Details of FAPI-46

CAS No. :2374782-04-2
Formula : C41H57F2N11O9
M.W : 885.96
SMILES Code : O=C(N1CCN(CCCN(C2=CC=C3N=CC=C(C(NCC(N4[C@H](C#N)CC(F)(F)C4)=O)=O)C3=C2)C)CC1)CN5CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC5
English Name :(S)-2,2',2''-(10-(2-(4-(3-((4-((2-(2-Cyano-4,4-difluoropyrrolidin-1-yl)-2-oxoethyl)carbamoyl)quinolin-6-yl)(methyl)amino)propyl)piperazin-1-yl)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid
MDL No. :MFCD34179074

Safety of FAPI-46

Application In Synthesis of FAPI-46

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 2374782-04-2 ]

[ 2374782-04-2 ] Synthesis Path-Downstream   1~11

  • 1
  • [ 2374782-78-0 ]
  • [ 2374782-04-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 10 steps 1.1: triethylamine / dichloromethane / 0.17 h / 0 °C 1.2: 1.5 h / 0 - 20 °C 2.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 4.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 5.1: lithium hydroxide; water / methanol / 24 h / 20 °C 6.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 6 h / 20 °C 7.1: lithium hydroxide; water / methanol / 24 h / 20 °C 8.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 9.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 10.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 10.2: 8 h / 20 °C
Multi-step reaction with 8 steps 1.1: triethylamine / dichloromethane / 0.17 h / 0 °C 1.2: 1.5 h / 0 - 20 °C 2.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 4.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 5.1: lithium hydroxide; water / methanol / 24 h / 20 °C 6.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 7.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 8.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 8.2: 8 h / 20 °C
Multi-step reaction with 9 steps 1.1: triethylamine / dichloromethane / 0.17 h / 0 °C 1.2: 1.5 h / 0 - 20 °C 2.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 4.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 5.1: lithium hydroxide; water / methanol / 24 h / 20 °C 6.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C 7.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 20 °C 7.2: 4 h / 20 °C 8.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 9.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 9.2: 8 h / 20 °C
Multi-step reaction with 7 steps 1: triethylamine 2: potassium iodide 3: trifluorormethanesulfonic acid; triisopropylsilane; trifluoroacetic acid / water 4: triethylamine 5: O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C 6: trifluoroacetic acid / acetonitrile 7: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C
Multi-step reaction with 7 steps 1.1: triethylamine / dichloromethane / 0.17 h / 0 °C 1.2: 1.5 h / 0 - 20 °C 2.1: triethylamine; potassium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 3.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 4.1: triethylamine / dichloromethane / 1 h / 0 - 20 °C 5.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 6.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 7.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 7.2: 8 h / 20 °C
Multi-step reaction with 8 steps 1.1: triethylamine / dichloromethane / 0.17 h / 0 °C 1.2: 1.5 h / 0 - 20 °C 2.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 4.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 5.1: lithium hydroxide / methanol; water / 24 h 6.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 7.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 8.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 8.2: 8 h / 20 °C
Multi-step reaction with 8 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 3.1: triethylamine / dichloromethane / 0.17 h / 0 °C 3.2: 1.5 h / 0 - 20 °C 4.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 5.1: lithium hydroxide / methanol; water / 24 h 6.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 7.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 8.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 8.2: 8 h / 20 °C
Multi-step reaction with 9 steps 1.1: triethylamine / dichloromethane / 0.17 h / 0 °C 1.2: 1.5 h / 0 - 20 °C 2.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 4.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 5.1: lithium hydroxide / methanol; water / 24 h 6.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 7.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 7.2: 2 h / 20 °C 8.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 9.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 9.2: 8 h / 20 °C
Multi-step reaction with 9 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 3.1: triethylamine / dichloromethane / 0.17 h / 0 °C 3.2: 1.5 h / 0 - 20 °C 4.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 5.1: lithium hydroxide / methanol; water / 24 h 6.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 7.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 7.2: 2 h / 20 °C 8.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 9.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 9.2: 8 h / 20 °C

  • 2
  • [ 3001301-25-0 ]
  • [ 2374782-04-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 2.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 3.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 4.1: lithium hydroxide; water / methanol / 24 h / 20 °C 5.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 6.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 7.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 7.2: 8 h / 20 °C
Multi-step reaction with 8 steps 1.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 2.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 3.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 4.1: lithium hydroxide; water / methanol / 24 h / 20 °C 5.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C 6.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 20 °C 6.2: 4 h / 20 °C 7.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 8.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 8.2: 8 h / 20 °C
Multi-step reaction with 9 steps 1.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 2.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 3.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 4.1: lithium hydroxide; water / methanol / 24 h / 20 °C 5.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 6 h / 20 °C 6.1: lithium hydroxide; water / methanol / 24 h / 20 °C 7.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 8.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 9.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 9.2: 8 h / 20 °C
Multi-step reaction with 6 steps 1: potassium iodide 2: trifluorormethanesulfonic acid; triisopropylsilane; trifluoroacetic acid / water 3: triethylamine 4: O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C 5: trifluoroacetic acid / acetonitrile 6: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C
Multi-step reaction with 6 steps 1.1: triethylamine; potassium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 2.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 3.1: triethylamine / dichloromethane / 1 h / 0 - 20 °C 4.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 5.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 6.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 6.2: 8 h / 20 °C
Multi-step reaction with 7 steps 1.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 2.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 3.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 4.1: lithium hydroxide / methanol; water / 24 h 5.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 6.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 7.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 7.2: 8 h / 20 °C
Multi-step reaction with 8 steps 1.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 2.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 3.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 4.1: lithium hydroxide / methanol; water / 24 h 5.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 6.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 6.2: 2 h / 20 °C 7.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 8.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 8.2: 8 h / 20 °C

  • 3
  • [ 87-48-9 ]
  • [ 2374782-04-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 10 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 4.1: copper(l) iodide; potassium carbonate; <i>L</i>-proline / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 5.1: triethylamine / dichloromethane / 0.17 h / 0 °C 5.2: 1.5 h / 0 - 20 °C 6.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 7.1: lithium hydroxide; water / methanol / 24 h / 20 °C 8.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 9.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 10.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 10.2: 8 h / 20 °C
Multi-step reaction with 11 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 4.1: copper(l) iodide; potassium carbonate; <i>L</i>-proline / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 5.1: triethylamine / dichloromethane / 0.17 h / 0 °C 5.2: 1.5 h / 0 - 20 °C 6.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 7.1: lithium hydroxide; water / methanol / 24 h / 20 °C 8.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C 9.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 20 °C 9.2: 4 h / 20 °C 10.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 11.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 11.2: 8 h / 20 °C
Multi-step reaction with 12 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 4.1: copper(l) iodide; potassium carbonate; <i>L</i>-proline / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 5.1: triethylamine / dichloromethane / 0.17 h / 0 °C 5.2: 1.5 h / 0 - 20 °C 6.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 7.1: lithium hydroxide; water / methanol / 24 h / 20 °C 8.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 6 h / 20 °C 9.1: lithium hydroxide; water / methanol / 24 h / 20 °C 10.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 11.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 12.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 12.2: 8 h / 20 °C
Multi-step reaction with 12 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: tetrahydrofuran / 0.5 h / 20 °C 3.2: 12 h / 20 °C 4.1: copper(l) iodide; potassium carbonate; <i>L</i>-proline / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 5.1: triethylamine / dichloromethane / 0.17 h / 0 °C 5.2: 1.5 h / 0 - 20 °C 6.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 7.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 8.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 9.1: lithium hydroxide; water / methanol / 24 h / 20 °C 10.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 11.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 12.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 12.2: 8 h / 20 °C
Multi-step reaction with 13 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: tetrahydrofuran / 0.5 h / 20 °C 3.2: 12 h / 20 °C 4.1: copper(l) iodide; potassium carbonate; <i>L</i>-proline / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 5.1: triethylamine / dichloromethane / 0.17 h / 0 °C 5.2: 1.5 h / 0 - 20 °C 6.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 7.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 8.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 9.1: lithium hydroxide; water / methanol / 24 h / 20 °C 10.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C 11.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 20 °C 11.2: 4 h / 20 °C 12.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 13.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 13.2: 8 h / 20 °C
Multi-step reaction with 14 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: tetrahydrofuran / 0.5 h / 20 °C 3.2: 12 h / 20 °C 4.1: copper(l) iodide; potassium carbonate; <i>L</i>-proline / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 5.1: triethylamine / dichloromethane / 0.17 h / 0 °C 5.2: 1.5 h / 0 - 20 °C 6.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 7.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 8.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 9.1: lithium hydroxide; water / methanol / 24 h / 20 °C 10.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 6 h / 20 °C 11.1: lithium hydroxide; water / methanol / 24 h / 20 °C 12.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 13.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 14.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 14.2: 8 h / 20 °C
Multi-step reaction with 10 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 4.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 5.1: triethylamine / dichloromethane / 0.17 h / 0 °C 5.2: 1.5 h / 0 - 20 °C 6.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 7.1: lithium hydroxide / methanol; water / 24 h 8.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 9.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 10.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 10.2: 8 h / 20 °C
Multi-step reaction with 11 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: tetrahydrofuran / 0.5 h / 20 °C 3.2: 12 h / 20 °C 4.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 5.1: triethylamine / dichloromethane / 0.17 h / 0 °C 5.2: 1.5 h / 0 - 20 °C 6.1: triethylamine; potassium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 7.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 8.1: triethylamine / dichloromethane / 1 h / 0 - 20 °C 9.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 10.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 11.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 11.2: 8 h / 20 °C
Multi-step reaction with 11 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: triethylamine / tetrahydrofuran / 50 °C 4.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 5.1: triethylamine / dichloromethane / 0.17 h / 0 °C 5.2: 1.5 h / 0 - 20 °C 6.1: triethylamine; potassium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 7.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 8.1: triethylamine / dichloromethane / 1 h / 0 - 20 °C 9.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 10.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 11.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 11.2: 8 h / 20 °C
Multi-step reaction with 11 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 4.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 5.1: triethylamine / dichloromethane / 0.17 h / 0 °C 5.2: 1.5 h / 0 - 20 °C 6.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 7.1: lithium hydroxide / methanol; water / 24 h 8.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 9.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 9.2: 2 h / 20 °C 10.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 11.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 11.2: 8 h / 20 °C
Multi-step reaction with 11 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 4.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 6.1: triethylamine / dichloromethane / 0.17 h / 0 °C 6.2: 1.5 h / 0 - 20 °C 7.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 8.1: lithium hydroxide / methanol; water / 24 h 9.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 10.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 11.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 11.2: 8 h / 20 °C
Multi-step reaction with 12 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: tetrahydrofuran / 0.5 h / 20 °C 3.2: 12 h / 20 °C 4.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 6.1: triethylamine / dichloromethane / 0.17 h / 0 °C 6.2: 1.5 h / 0 - 20 °C 7.1: triethylamine; potassium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 8.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 9.1: triethylamine / dichloromethane / 1 h / 0 - 20 °C 10.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 11.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 12.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 12.2: 8 h / 20 °C
Multi-step reaction with 12 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: triethylamine / tetrahydrofuran / 50 °C 4.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 6.1: triethylamine / dichloromethane / 0.17 h / 0 °C 6.2: 1.5 h / 0 - 20 °C 7.1: triethylamine; potassium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 8.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 9.1: triethylamine / dichloromethane / 1 h / 0 - 20 °C 10.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 11.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 12.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 12.2: 8 h / 20 °C
Multi-step reaction with 12 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 4.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 6.1: triethylamine / dichloromethane / 0.17 h / 0 °C 6.2: 1.5 h / 0 - 20 °C 7.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 8.1: lithium hydroxide / methanol; water / 24 h 9.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 10.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 10.2: 2 h / 20 °C 11.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 12.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 12.2: 8 h / 20 °C
Multi-step reaction with 12 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: tetrahydrofuran / 0.5 h / 20 °C 3.2: 12 h / 20 °C 4.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 5.1: triethylamine / dichloromethane / 0.17 h / 0 °C 5.2: 1.5 h / 0 - 20 °C 6.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 7.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 8.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 9.1: lithium hydroxide / methanol; water / 24 h 10.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 11.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 12.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 12.2: 8 h / 20 °C
Multi-step reaction with 12 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: triethylamine / tetrahydrofuran / 50 °C 4.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 5.1: triethylamine / dichloromethane / 0.17 h / 0 °C 5.2: 1.5 h / 0 - 20 °C 6.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 7.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 8.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 9.1: lithium hydroxide / methanol; water / 24 h 10.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 11.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 12.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 12.2: 8 h / 20 °C
Multi-step reaction with 12 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: tetrahydrofuran / 0.5 h / 20 °C 3.2: 12 h / 20 °C 4.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 5.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 6.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 7.1: triethylamine / dichloromethane / 0.17 h / 0 °C 7.2: 1.5 h / 0 - 20 °C 8.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 9.1: lithium hydroxide / methanol; water / 24 h 10.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 11.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 12.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 12.2: 8 h / 20 °C
Multi-step reaction with 12 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: triethylamine / tetrahydrofuran / 50 °C 4.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 5.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 6.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 7.1: triethylamine / dichloromethane / 0.17 h / 0 °C 7.2: 1.5 h / 0 - 20 °C 8.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 9.1: lithium hydroxide / methanol; water / 24 h 10.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 11.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 12.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 12.2: 8 h / 20 °C
Multi-step reaction with 13 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: tetrahydrofuran / 0.5 h / 20 °C 3.2: 12 h / 20 °C 4.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 5.1: triethylamine / dichloromethane / 0.17 h / 0 °C 5.2: 1.5 h / 0 - 20 °C 6.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 7.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 8.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 9.1: lithium hydroxide / methanol; water / 24 h 10.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 11.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 11.2: 2 h / 20 °C 12.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 13.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 13.2: 8 h / 20 °C
Multi-step reaction with 13 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: triethylamine / tetrahydrofuran / 50 °C 4.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 5.1: triethylamine / dichloromethane / 0.17 h / 0 °C 5.2: 1.5 h / 0 - 20 °C 6.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 7.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 8.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 9.1: lithium hydroxide / methanol; water / 24 h 10.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 11.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 11.2: 2 h / 20 °C 12.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 13.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 13.2: 8 h / 20 °C
Multi-step reaction with 13 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: tetrahydrofuran / 0.5 h / 20 °C 3.2: 12 h / 20 °C 4.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 5.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 6.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 7.1: triethylamine / dichloromethane / 0.17 h / 0 °C 7.2: 1.5 h / 0 - 20 °C 8.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 9.1: lithium hydroxide / methanol; water / 24 h 10.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 11.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 11.2: 2 h / 20 °C 12.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 13.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 13.2: 8 h / 20 °C
Multi-step reaction with 13 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: triethylamine / tetrahydrofuran / 50 °C 4.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 5.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 6.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 7.1: triethylamine / dichloromethane / 0.17 h / 0 °C 7.2: 1.5 h / 0 - 20 °C 8.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 9.1: lithium hydroxide / methanol; water / 24 h 10.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 11.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 11.2: 2 h / 20 °C 12.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 13.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 13.2: 8 h / 20 °C
Multi-step reaction with 13 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: tetrahydrofuran / 0.5 h / 20 °C 3.2: 12 h / 20 °C 4.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 6.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 7.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 8.1: triethylamine / dichloromethane / 0.17 h / 0 °C 8.2: 1.5 h / 0 - 20 °C 9.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 10.1: lithium hydroxide / methanol; water / 24 h 11.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 12.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 13.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 13.2: 8 h / 20 °C
Multi-step reaction with 13 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: triethylamine / tetrahydrofuran / 50 °C 4.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 6.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 7.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 8.1: triethylamine / dichloromethane / 0.17 h / 0 °C 8.2: 1.5 h / 0 - 20 °C 9.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 10.1: lithium hydroxide / methanol; water / 24 h 11.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 12.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 13.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 13.2: 8 h / 20 °C
Multi-step reaction with 13 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: tetrahydrofuran / 0.5 h / 20 °C 3.2: 12 h / 20 °C 4.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 6.1: triethylamine / dichloromethane / 0.17 h / 0 °C 6.2: 1.5 h / 0 - 20 °C 7.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 8.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 9.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 10.1: lithium hydroxide / methanol; water / 24 h 11.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 12.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 13.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 13.2: 8 h / 20 °C
Multi-step reaction with 13 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: triethylamine / tetrahydrofuran / 50 °C 4.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 6.1: triethylamine / dichloromethane / 0.17 h / 0 °C 6.2: 1.5 h / 0 - 20 °C 7.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 8.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 9.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 10.1: lithium hydroxide / methanol; water / 24 h 11.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 12.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 13.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 13.2: 8 h / 20 °C
Multi-step reaction with 14 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: tetrahydrofuran / 0.5 h / 20 °C 3.2: 12 h / 20 °C 4.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 6.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 7.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 8.1: triethylamine / dichloromethane / 0.17 h / 0 °C 8.2: 1.5 h / 0 - 20 °C 9.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 10.1: lithium hydroxide / methanol; water / 24 h 11.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 12.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 12.2: 2 h / 20 °C 13.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 14.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 14.2: 8 h / 20 °C
Multi-step reaction with 14 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: triethylamine / tetrahydrofuran / 50 °C 4.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 6.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 7.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 8.1: triethylamine / dichloromethane / 0.17 h / 0 °C 8.2: 1.5 h / 0 - 20 °C 9.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 10.1: lithium hydroxide / methanol; water / 24 h 11.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 12.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 12.2: 2 h / 20 °C 13.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 14.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 14.2: 8 h / 20 °C
Multi-step reaction with 14 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: tetrahydrofuran / 0.5 h / 20 °C 3.2: 12 h / 20 °C 4.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 6.1: triethylamine / dichloromethane / 0.17 h / 0 °C 6.2: 1.5 h / 0 - 20 °C 7.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 8.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 9.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 10.1: lithium hydroxide / methanol; water / 24 h 11.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 12.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 12.2: 2 h / 20 °C 13.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 14.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 14.2: 8 h / 20 °C
Multi-step reaction with 14 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: triethylamine / tetrahydrofuran / 50 °C 4.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 6.1: triethylamine / dichloromethane / 0.17 h / 0 °C 6.2: 1.5 h / 0 - 20 °C 7.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 8.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 9.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 10.1: lithium hydroxide / methanol; water / 24 h 11.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 12.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 12.2: 2 h / 20 °C 13.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 14.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 14.2: 8 h / 20 °C
Multi-step reaction with 8 steps 1.1: sodium hydroxide / water / 4 h / 110 °C 2.1: diphenylether / 5 h / 200 °C 3.1: caesium carbonate / acetonitrile / 12 h / 20 °C 4.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C 5.1: hydrogen; Pd/C / tetrahydrofuran / 12 h / 20 °C 6.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 7.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 8.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 8.2: 8 h / 20 °C

References: [1]Current Patent Assignee: NANJING MEDICAL UNIVERSITY - CN118791466, 2024, A.
[2]Current Patent Assignee: NANJING MEDICAL UNIVERSITY - CN118791466, 2024, A.
[3]Current Patent Assignee: NANJING MEDICAL UNIVERSITY - CN118791466, 2024, A.
[4]Current Patent Assignee: NANJING MEDICAL UNIVERSITY - CN118791466, 2024, A.
[5]Current Patent Assignee: NANJING MEDICAL UNIVERSITY - CN118791466, 2024, A.
[6]Current Patent Assignee: NANJING MEDICAL UNIVERSITY - CN118791466, 2024, A.
[7]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[8]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[9]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[10]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[11]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[12]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[13]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[14]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[15]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[16]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[17]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[18]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[19]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[20]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[21]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[22]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[23]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[24]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[25]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[26]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[27]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[28]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[29]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[30]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[31]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
  • 4
  • [ 3059678-42-8 ]
  • [ 2374782-04-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 2.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 3.1: lithium hydroxide; water / methanol / 24 h / 20 °C 4.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 5.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 6.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 6.2: 8 h / 20 °C
Multi-step reaction with 7 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 2.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 3.1: lithium hydroxide; water / methanol / 24 h / 20 °C 4.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C 5.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 20 °C 5.2: 4 h / 20 °C 6.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 7.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 7.2: 8 h / 20 °C
Multi-step reaction with 8 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 2.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 3.1: lithium hydroxide; water / methanol / 24 h / 20 °C 4.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 6 h / 20 °C 5.1: lithium hydroxide; water / methanol / 24 h / 20 °C 6.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 7.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 8.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 8.2: 8 h / 20 °C
Multi-step reaction with 6 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 2.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 3.1: lithium hydroxide / methanol; water / 24 h 4.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 5.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 6.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 6.2: 8 h / 20 °C
Multi-step reaction with 7 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 2.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 3.1: lithium hydroxide / methanol; water / 24 h 4.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 5.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 5.2: 2 h / 20 °C 6.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 7.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 7.2: 8 h / 20 °C

  • 5
  • [ 3059678-43-9 ]
  • [ 2374782-04-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 2.1: lithium hydroxide; water / methanol / 24 h / 20 °C 3.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 4.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 5.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 5.2: 8 h / 20 °C
Multi-step reaction with 6 steps 1.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 2.1: lithium hydroxide; water / methanol / 24 h / 20 °C 3.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C 4.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 20 °C 4.2: 4 h / 20 °C 5.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 6.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 6.2: 8 h / 20 °C
Multi-step reaction with 7 steps 1.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 2.1: lithium hydroxide; water / methanol / 24 h / 20 °C 3.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 6 h / 20 °C 4.1: lithium hydroxide; water / methanol / 24 h / 20 °C 5.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 6.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 7.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 7.2: 8 h / 20 °C
Multi-step reaction with 5 steps 1.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 2.1: lithium hydroxide / methanol; water / 24 h 3.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 4.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 5.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 5.2: 8 h / 20 °C
Multi-step reaction with 6 steps 1.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 2.1: lithium hydroxide / methanol; water / 24 h 3.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 4.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 4.2: 2 h / 20 °C 5.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 6.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 6.2: 8 h / 20 °C

  • 6
  • [ 3059678-44-0 ]
  • [ 2374782-04-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: lithium hydroxide; water / methanol / 24 h / 20 °C 2.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 3.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 4.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 4.2: 8 h / 20 °C
Multi-step reaction with 5 steps 1.1: lithium hydroxide; water / methanol / 24 h / 20 °C 2.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 20 °C 3.2: 4 h / 20 °C 4.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 5.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 5.2: 8 h / 20 °C
Multi-step reaction with 6 steps 1.1: lithium hydroxide; water / methanol / 24 h / 20 °C 2.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 6 h / 20 °C 3.1: lithium hydroxide; water / methanol / 24 h / 20 °C 4.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 5.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 6.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 6.2: 8 h / 20 °C
Multi-step reaction with 4 steps 1.1: lithium hydroxide / methanol; water / 24 h 2.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 3.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 4.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 4.2: 8 h / 20 °C
Multi-step reaction with 5 steps 1.1: lithium hydroxide / methanol; water / 24 h 2.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 3.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 3.2: 2 h / 20 °C 4.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 5.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 5.2: 8 h / 20 °C

  • 7
  • [ CAS Unavailable ]
  • [ 2374782-04-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 2.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 3.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 3.2: 8 h / 20 °C
Multi-step reaction with 4 steps 1.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C 2.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 20 °C 2.2: 4 h / 20 °C 3.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 4.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 4.2: 8 h / 20 °C
Multi-step reaction with 5 steps 1.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 6 h / 20 °C 2.1: lithium hydroxide; water / methanol / 24 h / 20 °C 3.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 4.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 5.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 5.2: 8 h / 20 °C
Multi-step reaction with 3 steps 1.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 2.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 3.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 3.2: 8 h / 20 °C
Multi-step reaction with 4 steps 1.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 2.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 2.2: 2 h / 20 °C 3.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 4.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 4.2: 8 h / 20 °C

  • 8
  • [ 1601063-72-2 ]
  • [ 2374782-04-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: copper(l) iodide; potassium carbonate; <i>L</i>-proline / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 0.17 h / 0 °C 2.2: 1.5 h / 0 - 20 °C 3.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 4.1: lithium hydroxide; water / methanol / 24 h / 20 °C 5.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 6.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 7.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 7.2: 8 h / 20 °C
Multi-step reaction with 8 steps 1.1: copper(l) iodide; potassium carbonate; <i>L</i>-proline / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 0.17 h / 0 °C 2.2: 1.5 h / 0 - 20 °C 3.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 4.1: lithium hydroxide; water / methanol / 24 h / 20 °C 5.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C 6.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 20 °C 6.2: 4 h / 20 °C 7.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 8.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 8.2: 8 h / 20 °C
Multi-step reaction with 9 steps 1.1: copper(l) iodide; potassium carbonate; <i>L</i>-proline / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 0.17 h / 0 °C 2.2: 1.5 h / 0 - 20 °C 3.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 4.1: lithium hydroxide; water / methanol / 24 h / 20 °C 5.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 6 h / 20 °C 6.1: lithium hydroxide; water / methanol / 24 h / 20 °C 7.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 8.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 9.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 9.2: 8 h / 20 °C
Multi-step reaction with 7 steps 1.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 0.17 h / 0 °C 2.2: 1.5 h / 0 - 20 °C 3.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 4.1: lithium hydroxide / methanol; water / 24 h 5.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 6.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 7.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 7.2: 8 h / 20 °C
Multi-step reaction with 8 steps 1.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 0.17 h / 0 °C 2.2: 1.5 h / 0 - 20 °C 3.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 4.1: lithium hydroxide / methanol; water / 24 h 5.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 6.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 6.2: 2 h / 20 °C 7.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 8.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 8.2: 8 h / 20 °C
Multi-step reaction with 8 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 3.1: triethylamine / dichloromethane / 0.17 h / 0 °C 3.2: 1.5 h / 0 - 20 °C 4.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 5.1: lithium hydroxide / methanol; water / 24 h 6.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 7.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 8.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 8.2: 8 h / 20 °C
Multi-step reaction with 9 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 3.1: triethylamine / dichloromethane / 0.17 h / 0 °C 3.2: 1.5 h / 0 - 20 °C 4.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 5.1: lithium hydroxide / methanol; water / 24 h 6.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 7.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 7.2: 2 h / 20 °C 8.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 9.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 9.2: 8 h / 20 °C

  • 9
  • [ 2883407-81-4 ]
  • [ 170908-81-3 ]
  • [ 2374782-04-2 ]
YieldReaction ConditionsOperation in experiment
74% Stage #1: (S)-N-(2-(2-cyano-4,4-difluoropyrrolidin-1-yl)-2-oxoethyl)-6-(methyl(3-(piperazin-1-yl)propyl)amino)quinoline-4-carboxamide With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 0.333333h; Stage #2: 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid mono(N-hydroxysuccinimidyl ester) In N,N-dimethyl-formamide at 20℃; for 8h;
22 mg Stage #1: (S)-N-(2-(2-cyano-4,4-difluoropyrrolidin-1-yl)-2-oxoethyl)-6-(methyl(3-(piperazin-1-yl)propyl)amino)quinoline-4-carboxamide With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 0.333333h; Stage #2: 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid mono(N-hydroxysuccinimidyl ester) In N,N-dimethyl-formamide at 20℃; for 8h; 20 (S)-2,2',2"-((10-(2-(4-(3-((4-((2-(2-cyano-4,4-difluoropyrrolidin-1-yl)-2-oxoethyl)carbamoyl)quinolin-6-yl)(methyl)amino)propyl)piperazin-1-yl)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid DIPEA (58 μL, 0.33 mmol) was added to a solution of (S)-N-(2-(2-cyano-4,4-difluoropyrrolidin-1-yl)-2-oxoethyl)-6-(methyl(3-(piperazin-1-yl)propyl)amino)quinoline-4-carboxamide (0.033 mmol) in anhydrous N,N-dimethylformamide (3 mL). After stirring at room temperature for 20 min, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid 1-(2,5-dioxo-1-pyrrolidinyl) ester (DOTA-NHS Ester) (17 mg, 0.033 mmol) was added and stirring at room temperature was continued for 8 h. The product was then separated by HPLC and lyophilized to obtain 22 mg of the title compound with a purity of 99% and a yield of 74%
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;
  • 10
  • [ 160233-76-1 ]
  • [ 2374782-04-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 10 steps 1.1: tetrahydrofuran / 0.5 h / 20 °C 1.2: 12 h / 20 °C 2.1: copper(l) iodide; potassium carbonate; <i>L</i>-proline / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 0.17 h / 0 °C 3.2: 1.5 h / 0 - 20 °C 4.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 5.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 6.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 7.1: lithium hydroxide; water / methanol / 24 h / 20 °C 8.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 9.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 10.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 10.2: 8 h / 20 °C
Multi-step reaction with 10 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 2.1: copper(l) iodide; potassium carbonate; <i>L</i>-proline / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 0.17 h / 0 °C 3.2: 1.5 h / 0 - 20 °C 4.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 5.1: lithium hydroxide; water / methanol / 24 h / 20 °C 6.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 6 h / 20 °C 7.1: lithium hydroxide; water / methanol / 24 h / 20 °C 8.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 9.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 10.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 10.2: 8 h / 20 °C
Multi-step reaction with 11 steps 1.1: tetrahydrofuran / 0.5 h / 20 °C 1.2: 12 h / 20 °C 2.1: copper(l) iodide; potassium carbonate; <i>L</i>-proline / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 0.17 h / 0 °C 3.2: 1.5 h / 0 - 20 °C 4.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 5.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 6.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 7.1: lithium hydroxide; water / methanol / 24 h / 20 °C 8.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C 9.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 20 °C 9.2: 4 h / 20 °C 10.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 11.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 11.2: 8 h / 20 °C
Multi-step reaction with 12 steps 1.1: tetrahydrofuran / 0.5 h / 20 °C 1.2: 12 h / 20 °C 2.1: copper(l) iodide; potassium carbonate; <i>L</i>-proline / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 0.17 h / 0 °C 3.2: 1.5 h / 0 - 20 °C 4.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 5.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 6.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 7.1: lithium hydroxide; water / methanol / 24 h / 20 °C 8.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 6 h / 20 °C 9.1: lithium hydroxide; water / methanol / 24 h / 20 °C 10.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 11.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 12.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 12.2: 8 h / 20 °C
Multi-step reaction with 8 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 2.1: copper(l) iodide; potassium carbonate; <i>L</i>-proline / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 0.17 h / 0 °C 3.2: 1.5 h / 0 - 20 °C 4.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 5.1: lithium hydroxide; water / methanol / 24 h / 20 °C 6.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 7.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 8.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 8.2: 8 h / 20 °C
Multi-step reaction with 9 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 2.1: copper(l) iodide; potassium carbonate; <i>L</i>-proline / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 0.17 h / 0 °C 3.2: 1.5 h / 0 - 20 °C 4.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 5.1: lithium hydroxide; water / methanol / 24 h / 20 °C 6.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C 7.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 20 °C 7.2: 4 h / 20 °C 8.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 9.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 9.2: 8 h / 20 °C
Multi-step reaction with 9 steps 1: perchloric acid 2: tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; caesium carbonate / toluene / 90 °C 3: triethylamine 4: potassium iodide 5: trifluorormethanesulfonic acid; triisopropylsilane; trifluoroacetic acid / water 6: triethylamine 7: O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C 8: trifluoroacetic acid / acetonitrile 9: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C
Multi-step reaction with 10 steps 1.1: tetrahydrofuran / 0.5 h / 20 °C 1.2: 12 h / 20 °C 2.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 4.1: triethylamine / dichloromethane / 0.17 h / 0 °C 4.2: 1.5 h / 0 - 20 °C 5.1: triethylamine; potassium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 6.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 7.1: triethylamine / dichloromethane / 1 h / 0 - 20 °C 8.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 9.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 10.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 10.2: 8 h / 20 °C
Multi-step reaction with 10 steps 1.1: tetrahydrofuran / 0.5 h / 20 °C 1.2: 12 h / 20 °C 2.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 0.17 h / 0 °C 3.2: 1.5 h / 0 - 20 °C 4.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 5.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 6.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 7.1: lithium hydroxide / methanol; water / 24 h 8.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 9.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 10.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 10.2: 8 h / 20 °C
Multi-step reaction with 10 steps 1.1: tetrahydrofuran / 0.5 h / 20 °C 1.2: 12 h / 20 °C 2.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 3.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 4.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 5.1: triethylamine / dichloromethane / 0.17 h / 0 °C 5.2: 1.5 h / 0 - 20 °C 6.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 7.1: lithium hydroxide / methanol; water / 24 h 8.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 9.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 10.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 10.2: 8 h / 20 °C
Multi-step reaction with 10 steps 1.1: triethylamine / tetrahydrofuran / 50 °C 2.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 4.1: triethylamine / dichloromethane / 0.17 h / 0 °C 4.2: 1.5 h / 0 - 20 °C 5.1: triethylamine; potassium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 6.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 7.1: triethylamine / dichloromethane / 1 h / 0 - 20 °C 8.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 9.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 10.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 10.2: 8 h / 20 °C
Multi-step reaction with 10 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 2.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 4.1: triethylamine / dichloromethane / 0.17 h / 0 °C 4.2: 1.5 h / 0 - 20 °C 5.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 6.1: lithium hydroxide / methanol; water / 24 h 7.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 8.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 8.2: 2 h / 20 °C 9.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 10.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 10.2: 8 h / 20 °C
Multi-step reaction with 10 steps 1.1: triethylamine / tetrahydrofuran / 50 °C 2.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 0.17 h / 0 °C 3.2: 1.5 h / 0 - 20 °C 4.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 5.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 6.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 7.1: lithium hydroxide / methanol; water / 24 h 8.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 9.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 10.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 10.2: 8 h / 20 °C
Multi-step reaction with 10 steps 1.1: triethylamine / tetrahydrofuran / 50 °C 2.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 3.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 4.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 5.1: triethylamine / dichloromethane / 0.17 h / 0 °C 5.2: 1.5 h / 0 - 20 °C 6.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 7.1: lithium hydroxide / methanol; water / 24 h 8.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 9.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 10.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 10.2: 8 h / 20 °C
Multi-step reaction with 11 steps 1.1: tetrahydrofuran / 0.5 h / 20 °C 1.2: 12 h / 20 °C 2.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 0.17 h / 0 °C 3.2: 1.5 h / 0 - 20 °C 4.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 5.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 6.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 7.1: lithium hydroxide / methanol; water / 24 h 8.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 9.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 9.2: 2 h / 20 °C 10.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 11.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 11.2: 8 h / 20 °C
Multi-step reaction with 11 steps 1.1: tetrahydrofuran / 0.5 h / 20 °C 1.2: 12 h / 20 °C 2.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 3.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 4.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 5.1: triethylamine / dichloromethane / 0.17 h / 0 °C 5.2: 1.5 h / 0 - 20 °C 6.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 7.1: lithium hydroxide / methanol; water / 24 h 8.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 9.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 9.2: 2 h / 20 °C 10.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 11.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 11.2: 8 h / 20 °C
Multi-step reaction with 11 steps 1.1: tetrahydrofuran / 0.5 h / 20 °C 1.2: 12 h / 20 °C 2.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 4.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 6.1: triethylamine / dichloromethane / 0.17 h / 0 °C 6.2: 1.5 h / 0 - 20 °C 7.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 8.1: lithium hydroxide / methanol; water / 24 h 9.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 10.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 11.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 11.2: 8 h / 20 °C
Multi-step reaction with 11 steps 1.1: tetrahydrofuran / 0.5 h / 20 °C 1.2: 12 h / 20 °C 2.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 4.1: triethylamine / dichloromethane / 0.17 h / 0 °C 4.2: 1.5 h / 0 - 20 °C 5.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 6.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 7.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 8.1: lithium hydroxide / methanol; water / 24 h 9.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 10.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 11.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 11.2: 8 h / 20 °C
Multi-step reaction with 11 steps 1.1: triethylamine / tetrahydrofuran / 50 °C 2.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 0.17 h / 0 °C 3.2: 1.5 h / 0 - 20 °C 4.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 5.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 6.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 7.1: lithium hydroxide / methanol; water / 24 h 8.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 9.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 9.2: 2 h / 20 °C 10.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 11.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 11.2: 8 h / 20 °C
Multi-step reaction with 11 steps 1.1: triethylamine / tetrahydrofuran / 50 °C 2.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 4.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 6.1: triethylamine / dichloromethane / 0.17 h / 0 °C 6.2: 1.5 h / 0 - 20 °C 7.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 8.1: lithium hydroxide / methanol; water / 24 h 9.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 10.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 11.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 11.2: 8 h / 20 °C
Multi-step reaction with 11 steps 1.1: triethylamine / tetrahydrofuran / 50 °C 2.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 4.1: triethylamine / dichloromethane / 0.17 h / 0 °C 4.2: 1.5 h / 0 - 20 °C 5.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 6.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 7.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 8.1: lithium hydroxide / methanol; water / 24 h 9.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 10.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 11.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 11.2: 8 h / 20 °C
Multi-step reaction with 11 steps 1.1: triethylamine / tetrahydrofuran / 50 °C 2.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 3.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 4.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 5.1: triethylamine / dichloromethane / 0.17 h / 0 °C 5.2: 1.5 h / 0 - 20 °C 6.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 7.1: lithium hydroxide / methanol; water / 24 h 8.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 9.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 9.2: 2 h / 20 °C 10.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 11.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 11.2: 8 h / 20 °C
Multi-step reaction with 12 steps 1.1: tetrahydrofuran / 0.5 h / 20 °C 1.2: 12 h / 20 °C 2.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 4.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 6.1: triethylamine / dichloromethane / 0.17 h / 0 °C 6.2: 1.5 h / 0 - 20 °C 7.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 8.1: lithium hydroxide / methanol; water / 24 h 9.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 10.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 10.2: 2 h / 20 °C 11.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 12.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 12.2: 8 h / 20 °C
Multi-step reaction with 12 steps 1.1: tetrahydrofuran / 0.5 h / 20 °C 1.2: 12 h / 20 °C 2.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 4.1: triethylamine / dichloromethane / 0.17 h / 0 °C 4.2: 1.5 h / 0 - 20 °C 5.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 6.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 7.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 8.1: lithium hydroxide / methanol; water / 24 h 9.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 10.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 10.2: 2 h / 20 °C 11.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 12.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 12.2: 8 h / 20 °C
Multi-step reaction with 12 steps 1.1: triethylamine / tetrahydrofuran / 50 °C 2.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 4.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 6.1: triethylamine / dichloromethane / 0.17 h / 0 °C 6.2: 1.5 h / 0 - 20 °C 7.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 8.1: lithium hydroxide / methanol; water / 24 h 9.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 10.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 10.2: 2 h / 20 °C 11.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 12.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 12.2: 8 h / 20 °C
Multi-step reaction with 12 steps 1.1: triethylamine / tetrahydrofuran / 50 °C 2.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 4.1: triethylamine / dichloromethane / 0.17 h / 0 °C 4.2: 1.5 h / 0 - 20 °C 5.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 6.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 7.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 8.1: lithium hydroxide / methanol; water / 24 h 9.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 10.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 10.2: 2 h / 20 °C 11.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 12.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 12.2: 8 h / 20 °C
Multi-step reaction with 6 steps 1.1: caesium carbonate / acetonitrile / 12 h / 20 °C 2.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C 3.1: hydrogen; Pd/C / tetrahydrofuran / 12 h / 20 °C 4.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 5.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 6.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 6.2: 8 h / 20 °C
Multi-step reaction with 8 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 2.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 0.17 h / 0 °C 3.2: 1.5 h / 0 - 20 °C 4.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 5.1: lithium hydroxide / methanol; water / 24 h 6.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 7.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 8.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 8.2: 8 h / 20 °C
Multi-step reaction with 9 steps 1.1: tetrahydrofuran / 0.5 h / 20 °C 1.2: 12 h / 20 °C 2.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 0.17 h / 0 °C 3.2: 1.5 h / 0 - 20 °C 4.1: triethylamine; potassium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 5.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 6.1: triethylamine / dichloromethane / 1 h / 0 - 20 °C 7.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 8.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 9.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 9.2: 8 h / 20 °C
Multi-step reaction with 9 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 2.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 4.1: triethylamine / dichloromethane / 0.17 h / 0 °C 4.2: 1.5 h / 0 - 20 °C 5.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 6.1: lithium hydroxide / methanol; water / 24 h 7.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 8.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 9.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 9.2: 8 h / 20 °C
Multi-step reaction with 9 steps 1.1: triethylamine / tetrahydrofuran / 50 °C 2.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 0.17 h / 0 °C 3.2: 1.5 h / 0 - 20 °C 4.1: triethylamine; potassium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 5.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 6.1: triethylamine / dichloromethane / 1 h / 0 - 20 °C 7.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 8.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 9.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 9.2: 8 h / 20 °C
Multi-step reaction with 9 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 2.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 0.17 h / 0 °C 3.2: 1.5 h / 0 - 20 °C 4.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 5.1: lithium hydroxide / methanol; water / 24 h 6.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 7.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 7.2: 2 h / 20 °C 8.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 9.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 9.2: 8 h / 20 °C

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[30]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[31]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[32]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
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  • [ 2374782-77-9 ]
  • [ 2374782-04-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 10 steps 1.1: copper(l) iodide; potassium carbonate; <i>L</i>-proline / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 0.17 h / 0 °C 2.2: 1.5 h / 0 - 20 °C 3.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 4.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 5.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 6.1: lithium hydroxide; water / methanol / 24 h / 20 °C 7.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C 8.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 20 °C 8.2: 4 h / 20 °C 9.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 10.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 10.2: 8 h / 20 °C
Multi-step reaction with 11 steps 1.1: copper(l) iodide; potassium carbonate; <i>L</i>-proline / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 0.17 h / 0 °C 2.2: 1.5 h / 0 - 20 °C 3.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 4.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 5.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 6.1: lithium hydroxide; water / methanol / 24 h / 20 °C 7.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 6 h / 20 °C 8.1: lithium hydroxide; water / methanol / 24 h / 20 °C 9.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 10.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 11.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 11.2: 8 h / 20 °C
Multi-step reaction with 9 steps 1.1: copper(l) iodide; potassium carbonate; <i>L</i>-proline / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 0.17 h / 0 °C 2.2: 1.5 h / 0 - 20 °C 3.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 4.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 5.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 6.1: lithium hydroxide; water / methanol / 24 h / 20 °C 7.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 8.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 9.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 9.2: 8 h / 20 °C
Multi-step reaction with 8 steps 1: tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; caesium carbonate / toluene / 90 °C 2: triethylamine 3: potassium iodide 4: trifluorormethanesulfonic acid; triisopropylsilane; trifluoroacetic acid / water 5: triethylamine 6: O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C 7: trifluoroacetic acid / acetonitrile 8: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C
Multi-step reaction with 10 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 3.1: triethylamine / dichloromethane / 0.17 h / 0 °C 3.2: 1.5 h / 0 - 20 °C 4.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 5.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 6.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 7.1: lithium hydroxide / methanol; water / 24 h 8.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 9.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 10.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 10.2: 8 h / 20 °C
Multi-step reaction with 10 steps 1.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 0.17 h / 0 °C 2.2: 1.5 h / 0 - 20 °C 3.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 4.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 5.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 6.1: lithium hydroxide / methanol; water / 24 h 7.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 8.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 8.2: 2 h / 20 °C 9.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 10.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 10.2: 8 h / 20 °C
Multi-step reaction with 10 steps 1.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 2.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 4.1: triethylamine / dichloromethane / 0.17 h / 0 °C 4.2: 1.5 h / 0 - 20 °C 5.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 6.1: lithium hydroxide / methanol; water / 24 h 7.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 8.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 8.2: 2 h / 20 °C 9.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 10.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 10.2: 8 h / 20 °C
Multi-step reaction with 10 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 3.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 4.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 5.1: triethylamine / dichloromethane / 0.17 h / 0 °C 5.2: 1.5 h / 0 - 20 °C 6.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 7.1: lithium hydroxide / methanol; water / 24 h 8.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 9.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 10.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 10.2: 8 h / 20 °C
Multi-step reaction with 11 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 3.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 4.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 5.1: triethylamine / dichloromethane / 0.17 h / 0 °C 5.2: 1.5 h / 0 - 20 °C 6.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 7.1: lithium hydroxide / methanol; water / 24 h 8.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 9.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 9.2: 2 h / 20 °C 10.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 11.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 11.2: 8 h / 20 °C
Multi-step reaction with 11 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 3.1: triethylamine / dichloromethane / 0.17 h / 0 °C 3.2: 1.5 h / 0 - 20 °C 4.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 5.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 6.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 7.1: lithium hydroxide / methanol; water / 24 h 8.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 2 h / 0 °C / Cooling with ice 9.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h / 20 °C 9.2: 2 h / 20 °C 10.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 11.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 11.2: 8 h / 20 °C
Multi-step reaction with 8 steps 1.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 0.17 h / 0 °C 2.2: 1.5 h / 0 - 20 °C 3.1: triethylamine; potassium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 4.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 5.1: triethylamine / dichloromethane / 1 h / 0 - 20 °C 6.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 7.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 8.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 8.2: 8 h / 20 °C
Multi-step reaction with 9 steps 1.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 0.17 h / 0 °C 2.2: 1.5 h / 0 - 20 °C 3.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 4.1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 5.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 6.1: lithium hydroxide / methanol; water / 24 h 7.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 8.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 9.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 9.2: 8 h / 20 °C
Multi-step reaction with 9 steps 1.1: <i>L</i>-proline; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 10 h / 100 °C / Inert atmosphere 2.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.5 h / 20 °C 4.1: triethylamine / dichloromethane / 0.17 h / 0 °C 4.2: 1.5 h / 0 - 20 °C 5.1: potassium carbonate; sodium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 6.1: lithium hydroxide / methanol; water / 24 h 7.1: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate; 1-methyl-1H-imidazole / acetonitrile / 12 h / 20 °C 8.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 9.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 9.2: 8 h / 20 °C
Multi-step reaction with 9 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 3.1: triethylamine / dichloromethane / 0.17 h / 0 °C 3.2: 1.5 h / 0 - 20 °C 4.1: triethylamine; potassium iodide / N,N-dimethyl-formamide / 2.5 h / 70 °C 5.1: trifluoroacetic acid; triisopropylsilane; trifluorormethanesulfonic acid / dichloromethane / 1 h / 0 - 20 °C 6.1: triethylamine / dichloromethane / 1 h / 0 - 20 °C 7.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 8.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 9.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.33 h / 20 °C 9.2: 8 h / 20 °C

References: [1]Current Patent Assignee: NANJING MEDICAL UNIVERSITY - CN118791466, 2024, A.
[2]Current Patent Assignee: NANJING MEDICAL UNIVERSITY - CN118791466, 2024, A.
[3]Current Patent Assignee: NANJING MEDICAL UNIVERSITY - CN118791466, 2024, A.
[4]Brake, Katie; Matus-Meza, Audifás-Salvador; Rawat, Purnima; Rikhtechi, Pedram; Sadi, Kiana Sherkat; Garrison, Jered C. [Nuclear Medicine and Biology, 2025, vol. 146-147].
[5]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[6]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[7]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[8]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[9]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[10]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[11]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[12]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[13]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
[14]Lu, Zhipeng; Hu, Yan; Xu, Benqin; Liao, Chenhao; Sun, Jialin; Li, Tingyou; Chen, Panpan [Organic Process Research and Development, 2025, vol. 29, # 12, p. 3138 - 3149].
 

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