*Storage: {[sel_prStorage]}
*Shipping: {[sel_prShipping]}
The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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.
Change View
| Size | Price | VIP Price |
DE Stock US Stock |
Asia Stock Global Stock |
In Stock |
| {[ item.pr_size ]}{[ size_append_text(item.pr_size, proInfo.prAm, 'list') ]} |
Inquiry
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price, item.discount_usd) ]} {[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]} |
Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]} | {[ item.p_spot_brand_remark ]} 1-2 weeks {[ item.pr_usastock ]} In Stock Inquiry - | {[ item.p_spot_brand_remark ]} 1-2 weeks {[ item.pr_chinastock ]} {[ item.pr_remark ]} In Stock Inquiry - | Login - + |
Please Login or Create an Account to: See VIP prices and availability
Asia Stock: Ship in 3-5 business days
EU Stock: ship in 0-1 business day
Global Stock: ship in 7-10 days
US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days
{[ item.p_spot_brand_remark ]}
1-2weeks
Inquiry
Inquiry
{[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ getRatePrice(item.pr_usd,1,item.mem_rate,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ item.p_spot_brand_remark ]}
1-2weeks
Inquiry
Inquiry
{[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price, item.vip_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
In Stock
- +
Please Login or Create an Account to: See VIP prices and availability
Asia Stock: Ship in 3-5 business days
EU Stock: ship in 0-1 business day
Global Stock: ship in 7-10 days
US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
| 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 |
* 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.

| Yield | Reaction Conditions | Operation 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 |

| Yield | Reaction Conditions | Operation 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 |

| Yield | Reaction Conditions | Operation 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 |

| Yield | Reaction Conditions | Operation 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 |

| Yield | Reaction Conditions | Operation 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 |

| Yield | Reaction Conditions | Operation 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 |

| Yield | Reaction Conditions | Operation 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 |

| Yield | Reaction Conditions | Operation 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 |

| Yield | Reaction Conditions | Operation 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℃; |
| Yield | Reaction Conditions | Operation 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 |

| Yield | Reaction Conditions | Operation 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 |
