Alternatived Products of [ 3956-34-1 ]
Product Details of [ 3956-34-1 ]
| CAS No. : | 3956-34-1 |
MDL No. : | MFCD18642897 |
| Formula : |
C10H13NO4
|
Boiling Point : |
- |
| Linear Structure Formula : | - |
InChI Key : | ULKQAFJENDMZMB-UHFFFAOYSA-N |
| M.W : |
211.21
|
Pubchem ID : | 58907369 |
| Synonyms : |
|
Application In Synthesis of [ 3956-34-1 ]
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
- Downstream synthetic route of [ 3956-34-1 ]
- 1
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[ 3956-34-1 ]
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[ 120728-10-1 ]
-
[ 874676-72-9 ]
| Yield | Reaction Conditions | Operation in experiment |
| 71% |
|
Step 1; Methyl 4-amino-2,6-dimethoxybenzoate 11-1 (2.00 g, 9.5 mmol), prepared by themethod of Broadhurst et al. (J. Chem. Soc. 1977, 2502), was dissolved in DMSO (20ml_). N-Boc-1-aminocyclobutane-1-carboxylic acid (2.07 g, 9.6 mmol) was addedfollowed by triethylamine (4.18 ml_, 30 mmol, 3.2 equivalents) and TBTU (3.69 g, 11.5mmol, 1.2 equivalent). The mixture was stirred for 24 h at room temperature afterwhich it was added dropwise to a solution of AcOH (15 ml_) in water (150 ml). Thewhite precipitate 11-2 was collected by filtration, washed with water and dried invacuum (3.50 g, 71% yield): MS m/z 409.3 (MH*). |
- 2
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[ 3956-34-1 ]
-
[ 1441208-08-7 ]
| Yield | Reaction Conditions | Operation in experiment |
| 20% |
With Selectfluor In acetonitrile at 0℃; for 0.5h; |
10 Preparation 10: methyl 4-amino-3-fluoro-2,6-dimethoxybenzoate
To a solution of methyl 4-amino-2,6-dimethoxybenzoate (510 mg, 2.42 mmol) in acetonitrile (10 mL) at 0°C was added Selectfluor (940 mg, 2.66 mmol). The mixture was stirred 30 minutes at 0°C then water (10 mL) was added. The reaction was extracted twice with ethyl acetate (30 mL). The organic phases were combined, passed through a hydrophobic frit and the solvent was removed in vacuo. Purification of the residue via silica gel column chromatography (0-100% EtOAc in iso-hexane) gave methyl 4-amino- 3-fluoro-2,6-dimethoxybenzoate (114 mg, 20 %) as a yellow solid. Ή NMR (400 MHz, CDC13): δ 6.05 (d, J = 6.4 Hz, 1H), 3.93 (s, 3H), 3.88 (s, 3H), 3.75 (s, 3H). |
- 3
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[ 3956-34-1 ]
-
[ 1441199-61-6 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 2 steps
1.1: Selectfluor / acetonitrile / 0.5 h / 0 °C
2.1: sodium hydroxide / ethanol / 18 h / 60 °C
2.2: 1 h / 20 °C
2.3: 0.5 h / 100 °C |
|
- 4
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[ 3956-34-1 ]
-
C37H40N4O6
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 6 steps
1.1: triethylamine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate / dimethyl sulfoxide / 24 h / 20 °C / Inert atmosphere
2.1: lithium aluminium tetrahydride / tetrahydrofuran / 3.5 h / 0 - 20 °C / Inert atmosphere
3.1: manganese(IV) oxide / tetrahydrofuran / 24 h / Reflux; Inert atmosphere
4.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 20 °C / Inert atmosphere
4.2: 0.5 h / 20 °C / Inert atmosphere
5.1: hydrogenchloride / 1,4-dioxane / 20 °C / Inert atmosphere
6.1: triethylamine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate / dimethyl sulfoxide / 2 h / 20 °C / Inert atmosphere |
|
Reference：
[1]Beaulieu, Pierre L.; Anderson, Paul C.; Bethell, Richard; Bös, Michael; Bousquet, Yves; Brochu, Christian; Cordingley, Michael G.; Fazal, Gulrez; Garneau, Michel; Gillard, James R.; Kawai, Stephen; Marquis, Martin; McKercher, Ginette; Poupart, Marc-André; Stammers, Timothy; Thavonekham, Bounkham; Wernic, Dominik; Duan, Jianmin; Kukolj, George
[Journal of Medicinal Chemistry, 2014, vol. 57, # 23, p. 10130 - 10143]
- 5
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[ 3956-34-1 ]
-
[ 874676-73-0 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 2 steps
1: triethylamine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate / dimethyl sulfoxide / 24 h / 20 °C / Inert atmosphere
2: lithium aluminium tetrahydride / tetrahydrofuran / 3.5 h / 0 - 20 °C / Inert atmosphere |
|
Reference：
[1]Beaulieu, Pierre L.; Anderson, Paul C.; Bethell, Richard; Bös, Michael; Bousquet, Yves; Brochu, Christian; Cordingley, Michael G.; Fazal, Gulrez; Garneau, Michel; Gillard, James R.; Kawai, Stephen; Marquis, Martin; McKercher, Ginette; Poupart, Marc-André; Stammers, Timothy; Thavonekham, Bounkham; Wernic, Dominik; Duan, Jianmin; Kukolj, George
[Journal of Medicinal Chemistry, 2014, vol. 57, # 23, p. 10130 - 10143]
- 6
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[ 3956-34-1 ]
-
[ 874676-74-1 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 3 steps
1: triethylamine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate / dimethyl sulfoxide / 24 h / 20 °C / Inert atmosphere
2: lithium aluminium tetrahydride / tetrahydrofuran / 3.5 h / 0 - 20 °C / Inert atmosphere
3: manganese(IV) oxide / tetrahydrofuran / 24 h / Reflux; Inert atmosphere |
|
Reference：
[1]Beaulieu, Pierre L.; Anderson, Paul C.; Bethell, Richard; Bös, Michael; Bousquet, Yves; Brochu, Christian; Cordingley, Michael G.; Fazal, Gulrez; Garneau, Michel; Gillard, James R.; Kawai, Stephen; Marquis, Martin; McKercher, Ginette; Poupart, Marc-André; Stammers, Timothy; Thavonekham, Bounkham; Wernic, Dominik; Duan, Jianmin; Kukolj, George
[Journal of Medicinal Chemistry, 2014, vol. 57, # 23, p. 10130 - 10143]
- 7
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[ 3956-34-1 ]
-
C17H22N2O5*ClH
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 5 steps
1.1: triethylamine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate / dimethyl sulfoxide / 24 h / 20 °C / Inert atmosphere
2.1: lithium aluminium tetrahydride / tetrahydrofuran / 3.5 h / 0 - 20 °C / Inert atmosphere
3.1: manganese(IV) oxide / tetrahydrofuran / 24 h / Reflux; Inert atmosphere
4.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 20 °C / Inert atmosphere
4.2: 0.5 h / 20 °C / Inert atmosphere
5.1: hydrogenchloride / 1,4-dioxane / 20 °C / Inert atmosphere |
|
Reference：
[1]Beaulieu, Pierre L.; Anderson, Paul C.; Bethell, Richard; Bös, Michael; Bousquet, Yves; Brochu, Christian; Cordingley, Michael G.; Fazal, Gulrez; Garneau, Michel; Gillard, James R.; Kawai, Stephen; Marquis, Martin; McKercher, Ginette; Poupart, Marc-André; Stammers, Timothy; Thavonekham, Bounkham; Wernic, Dominik; Duan, Jianmin; Kukolj, George
[Journal of Medicinal Chemistry, 2014, vol. 57, # 23, p. 10130 - 10143]
- 8
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[ 3956-34-1 ]
-
[ 874676-75-2 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 4 steps
1.1: triethylamine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate / dimethyl sulfoxide / 24 h / 20 °C / Inert atmosphere
2.1: lithium aluminium tetrahydride / tetrahydrofuran / 3.5 h / 0 - 20 °C / Inert atmosphere
3.1: manganese(IV) oxide / tetrahydrofuran / 24 h / Reflux; Inert atmosphere
4.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 20 °C / Inert atmosphere
4.2: 0.5 h / 20 °C / Inert atmosphere |
|
Reference：
[1]Beaulieu, Pierre L.; Anderson, Paul C.; Bethell, Richard; Bös, Michael; Bousquet, Yves; Brochu, Christian; Cordingley, Michael G.; Fazal, Gulrez; Garneau, Michel; Gillard, James R.; Kawai, Stephen; Marquis, Martin; McKercher, Ginette; Poupart, Marc-André; Stammers, Timothy; Thavonekham, Bounkham; Wernic, Dominik; Duan, Jianmin; Kukolj, George
[Journal of Medicinal Chemistry, 2014, vol. 57, # 23, p. 10130 - 10143]
- 9
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[ 3956-34-1 ]
-
C36H38N4O6
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 7 steps
1.1: triethylamine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate / dimethyl sulfoxide / 24 h / 20 °C / Inert atmosphere
2.1: lithium aluminium tetrahydride / tetrahydrofuran / 3.5 h / 0 - 20 °C / Inert atmosphere
3.1: manganese(IV) oxide / tetrahydrofuran / 24 h / Reflux; Inert atmosphere
4.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 20 °C / Inert atmosphere
4.2: 0.5 h / 20 °C / Inert atmosphere
5.1: hydrogenchloride / 1,4-dioxane / 20 °C / Inert atmosphere
6.1: triethylamine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate / dimethyl sulfoxide / 2 h / 20 °C / Inert atmosphere
7.1: sodium hydroxide / dimethyl sulfoxide; methanol / 2 h / 20 °C / Inert atmosphere
7.2: Inert atmosphere |
|
Reference：
[1]Beaulieu, Pierre L.; Anderson, Paul C.; Bethell, Richard; Bös, Michael; Bousquet, Yves; Brochu, Christian; Cordingley, Michael G.; Fazal, Gulrez; Garneau, Michel; Gillard, James R.; Kawai, Stephen; Marquis, Martin; McKercher, Ginette; Poupart, Marc-André; Stammers, Timothy; Thavonekham, Bounkham; Wernic, Dominik; Duan, Jianmin; Kukolj, George
[Journal of Medicinal Chemistry, 2014, vol. 57, # 23, p. 10130 - 10143]
- 10
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[ 3956-34-1 ]
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4-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-2,6-dimethoxy-N-(2-(4-methylpiperazin-1-yl)ethyl)benzamide
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 5 steps
1: sodium hydroxide; water / methanol / 16 h / 60 °C
2: triethylamine / water; 1,4-dioxane / 16 h
3: HATU; N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / 20 °C
4: trifluoroacetic acid
5: potassium carbonate; chloro[2-(dicyclohexylphosphino)-3 ,6-dimethoxy-2’,4’, 6’-triisopropyl- 1,1’-biphenyl] [2-(2-aminoethyl)phenyl]palladium(II) / N,N-dimethyl-formamide / 1 h / 85 °C / Inert atmosphere |
|
- 11
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[ 3956-34-1 ]
-
4-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-2,6-dimethoxy-N-(3-morpholinopropyl)benzamide
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 5 steps
1: sodium hydroxide; water / methanol / 16 h / 60 °C
2: triethylamine / water; 1,4-dioxane / 16 h
3: HATU; N-ethyl-N,N-diisopropylamine / dichloromethane; water / 16 h / 20 °C
4: trifluoroacetic acid / dichloromethane
5: potassium carbonate; chloro[2-(dicyclohexylphosphino)-3 ,6-dimethoxy-2’,4’, 6’-triisopropyl- 1,1’-biphenyl] [2-(2-aminoethyl)phenyl]palladium(II) / N,N-dimethyl-formamide / 1 h / 85 °C / Inert atmosphere |
|
- 12
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[ 3956-34-1 ]
-
4-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-N-(2-(2-(2-hydroxyethoxy)ethoxy)ethyl)-2,6-dimethoxybenzamide
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 5 steps
1.1: sodium hydroxide; water / methanol / 16 h / 60 °C
2.1: triethylamine / water; 1,4-dioxane / 16 h
3.1: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide; dichloromethane / 16 h / 20 °C
4.1: trifluoroacetic acid / dichloromethane / 75 h
4.2: 1 h / Reflux
5.1: potassium carbonate; chloro[2-(dicyclohexylphosphino)-3 ,6-dimethoxy-2’,4’, 6’-triisopropyl- 1,1’-biphenyl] [2-(2-aminoethyl)phenyl]palladium(II) / N,N-dimethyl-formamide / 1 h / 85 °C / Inert atmosphere |
|
- 13
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[ 3956-34-1 ]
-
4-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-(2-hydroxyethyl)piperazin-1-yl)ethyl)-2,6-dimethoxybenzamide
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 5 steps
1: sodium hydroxide; water / methanol / 16 h / 60 °C
2: triethylamine / water; 1,4-dioxane / 16 h
3: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide; dichloromethane / 16 h / 20 °C
4: dichloromethane / 72 h
5: potassium carbonate; chloro[2-(dicyclohexylphosphino)-3 ,6-dimethoxy-2’,4’, 6’-triisopropyl- 1,1’-biphenyl] [2-(2-aminoethyl)phenyl]palladium(II) / N,N-dimethyl-formamide / 16 h / 85 °C / Inert atmosphere |
|
- 14
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[ 3956-34-1 ]
-
4-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-N-(2-(dimethylamino)ethyl)-2,6-dimethoxybenzamide
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 5 steps
1: sodium hydroxide; water / methanol / 16 h / 60 °C
2: triethylamine / water; 1,4-dioxane / 16 h
3: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C
4: dichloromethane / 16 h
5: potassium carbonate; chloro[2-(dicyclohexylphosphino)-3 ,6-dimethoxy-2’,4’, 6’-triisopropyl- 1,1’-biphenyl] [2-(2-aminoethyl)phenyl]palladium(II) / N,N-dimethyl-formamide / 20 h / 80 - 85 °C / Inert atmosphere |
|
- 15
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[ 3956-34-1 ]
-
sodium 4-amino-2,6-dimethoxybenzoate
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
| 1.75 g |
With water; sodium hydroxide In methanol at 60℃; for 16h; |
22.i (i) Sodium 4-amino-2,6-dimethoxybenzoate
(i) Sodium 4-amino-2,6-dimethoxybenzoate NaOH solution 50%w/w (4 mL, 76 mmol) was added to a solution of methyl 4-amino-2,6- dimethoxybenzoate (2 g, 9.47 mmol) in MeOH (40 mL). The reaction was heated at 60°C (block temperature) for 16h. The reaction mixture was cooled in an ice bath filtered and washed with ice cold methanol (1 mL) then dried to constant weight to afford the sub-title compound (1.75 g) as a tan crystalline solid. LCMS m/z 198 (M+H)+ (ES+) |
- 16
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[ 3956-34-1 ]
-
4-((tert-butoxycarbonyl)amino)-2,6-dimethoxybenzoic acid
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 2 steps
1: sodium hydroxide; water / methanol / 16 h / 60 °C
2: triethylamine / water; 1,4-dioxane / 16 h |
|
- 17
-
[ 3956-34-1 ]
-
tert-butyl (3,5-dimethoxy-4-((2-(4-methylpiperazin-1-yl)ethyl)carbamoyl)phenyl)carbamate
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 3 steps
1: sodium hydroxide; water / methanol / 16 h / 60 °C
2: triethylamine / water; 1,4-dioxane / 16 h
3: HATU; N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / 20 °C |
|
- 18
-
[ 3956-34-1 ]
-
4-amino-2,6-dimethoxy-N-(2-(4-methylpiperazin-1-yl)ethyl)benzamide
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 4 steps
1: sodium hydroxide; water / methanol / 16 h / 60 °C
2: triethylamine / water; 1,4-dioxane / 16 h
3: HATU; N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / 20 °C
4: trifluoroacetic acid |
|
- 19
-
[ 3956-34-1 ]
-
tert-butyl (3,5-dimethoxy-4-((3-morpholinopropyl)carbamoyl)phenyl)carbamate
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 3 steps
1: sodium hydroxide; water / methanol / 16 h / 60 °C
2: triethylamine / water; 1,4-dioxane / 16 h
3: HATU; N-ethyl-N,N-diisopropylamine / dichloromethane; water / 16 h / 20 °C |
|
- 20
-
[ 3956-34-1 ]
-
4-amino-2,6-dimethoxy-N-(3-morpholinopropyl)benzamide
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 4 steps
1: sodium hydroxide; water / methanol / 16 h / 60 °C
2: triethylamine / water; 1,4-dioxane / 16 h
3: HATU; N-ethyl-N,N-diisopropylamine / dichloromethane; water / 16 h / 20 °C
4: trifluoroacetic acid / dichloromethane |
|
- 21
-
[ 3956-34-1 ]
-
tert-butyl (4-((2-(2-(2-hydroxyethoxy)ethoxy)ethyl)carbamoyl)-3,5-dimethoxyphenyl)carbamate
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 3 steps
1: sodium hydroxide; water / methanol / 16 h / 60 °C
2: triethylamine / water; 1,4-dioxane / 16 h
3: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide; dichloromethane / 16 h / 20 °C |
|
- 22
-
[ 3956-34-1 ]
-
4-amino-N-(2-(2-(2-hydroxyethoxy)ethoxy)ethyl)-2,6-dimethoxybenzamide
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 4 steps
1.1: sodium hydroxide; water / methanol / 16 h / 60 °C
2.1: triethylamine / water; 1,4-dioxane / 16 h
3.1: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide; dichloromethane / 16 h / 20 °C
4.1: trifluoroacetic acid / dichloromethane / 75 h
4.2: 1 h / Reflux |
|
- 23
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[ 3956-34-1 ]
-
tert-butyl (4-((2-(4-(2-hydroxyethyl)piperazin-1-yl)ethyl)carbamoyl)-3,5-dimethoxyphenyl)carbamate
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 3 steps
1: sodium hydroxide; water / methanol / 16 h / 60 °C
2: triethylamine / water; 1,4-dioxane / 16 h
3: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide; dichloromethane / 16 h / 20 °C |
|
- 24
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[ 3956-34-1 ]
-
4-amino-N-(2-(4-(2-hydroxyethyl)piperazin-1-yl)ethyl)-2,6-dimethoxybenzamide difluoroacetate
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 4 steps
1: sodium hydroxide; water / methanol / 16 h / 60 °C
2: triethylamine / water; 1,4-dioxane / 16 h
3: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide; dichloromethane / 16 h / 20 °C
4: dichloromethane / 72 h |
|
- 25
-
[ 3956-34-1 ]
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tert-butyl (4-((2-(dimethylamino)ethyl)carbamoyl)-3,5-dimethoxyphenyl)carbamate
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 3 steps
1: sodium hydroxide; water / methanol / 16 h / 60 °C
2: triethylamine / water; 1,4-dioxane / 16 h
3: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C |
|
- 26
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[ 3956-34-1 ]
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4-amino-N-(2-(dimethylamino)ethyl)-2,6-dimethoxybenzamide bis(trifluoroacetate)
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 4 steps
1: sodium hydroxide; water / methanol / 16 h / 60 °C
2: triethylamine / water; 1,4-dioxane / 16 h
3: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C
4: dichloromethane / 16 h |
|
- 27
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[ 3956-34-1 ]
-
dibenzyl (2-(2-(2-(4-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-2,6-dimethoxybenzamido)ethoxy)ethoxy)ethyl) phosphate
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 7 steps
1.1: sodium hydroxide; water / methanol / 16 h / 60 °C
2.1: triethylamine / water; 1,4-dioxane / 16 h
3.1: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide; dichloromethane / 16 h / 20 °C
4.1: trifluoroacetic acid / dichloromethane / 75 h
4.2: 1 h / Reflux
5.1: potassium carbonate; chloro[2-(dicyclohexylphosphino)-3 ,6-dimethoxy-2’,4’, 6’-triisopropyl- 1,1’-biphenyl] [2-(2-aminoethyl)phenyl]palladium(II) / N,N-dimethyl-formamide / 1 h / 85 °C / Inert atmosphere
6.1: 5-methyl-1,2,3,4-tetrazole / N,N-dimethyl-formamide; tetrahydrofuran / 22 h / 20 °C
7.1: dihydrogen peroxide / N,N-dimethyl-formamide; tetrahydrofuran; water / 1 h / 0 - 20 °C |
|
- 28
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[ 3956-34-1 ]
-
C57H65N6O13PS
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 6 steps
1.1: sodium hydroxide; water / methanol / 16 h / 60 °C
2.1: triethylamine / water; 1,4-dioxane / 16 h
3.1: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide; dichloromethane / 16 h / 20 °C
4.1: trifluoroacetic acid / dichloromethane / 75 h
4.2: 1 h / Reflux
5.1: potassium carbonate; chloro[2-(dicyclohexylphosphino)-3 ,6-dimethoxy-2’,4’, 6’-triisopropyl- 1,1’-biphenyl] [2-(2-aminoethyl)phenyl]palladium(II) / N,N-dimethyl-formamide / 1 h / 85 °C / Inert atmosphere
6.1: 5-methyl-1,2,3,4-tetrazole / N,N-dimethyl-formamide; tetrahydrofuran / 22 h / 20 °C |
|
- 29
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[ 3956-34-1 ]
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2-(2-(2-(4-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-2,6-dimethoxybenzamido)ethoxy)ethoxy)ethyl dihydrogenphosphate disodium salt
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 8 steps
1.1: sodium hydroxide; water / methanol / 16 h / 60 °C
2.1: triethylamine / water; 1,4-dioxane / 16 h
3.1: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide; dichloromethane / 16 h / 20 °C
4.1: trifluoroacetic acid / dichloromethane / 75 h
4.2: 1 h / Reflux
5.1: potassium carbonate; chloro[2-(dicyclohexylphosphino)-3 ,6-dimethoxy-2’,4’, 6’-triisopropyl- 1,1’-biphenyl] [2-(2-aminoethyl)phenyl]palladium(II) / N,N-dimethyl-formamide / 1 h / 85 °C / Inert atmosphere
6.1: 5-methyl-1,2,3,4-tetrazole / N,N-dimethyl-formamide; tetrahydrofuran / 22 h / 20 °C
7.1: dihydrogen peroxide / N,N-dimethyl-formamide; tetrahydrofuran; water / 1 h / 0 - 20 °C
8.1: sodium hydrogencarbonate; hydrogen; 5%-palladium/activated carbon / tetrahydrofuran; water; methanol / 3750.38 Torr |
|
- 30
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[ 3956-34-1 ]
-
2-(2-(2-(4-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-2,6-dimethoxybenzamido)ethoxy)ethoxy)ethyl dihydrogenphosphate monosodium salt
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 8 steps
1.1: sodium hydroxide; water / methanol / 16 h / 60 °C
2.1: triethylamine / water; 1,4-dioxane / 16 h
3.1: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide; dichloromethane / 16 h / 20 °C
4.1: trifluoroacetic acid / dichloromethane / 75 h
4.2: 1 h / Reflux
5.1: potassium carbonate; chloro[2-(dicyclohexylphosphino)-3 ,6-dimethoxy-2’,4’, 6’-triisopropyl- 1,1’-biphenyl] [2-(2-aminoethyl)phenyl]palladium(II) / N,N-dimethyl-formamide / 1 h / 85 °C / Inert atmosphere
6.1: 5-methyl-1,2,3,4-tetrazole / N,N-dimethyl-formamide; tetrahydrofuran / 22 h / 20 °C
7.1: dihydrogen peroxide / N,N-dimethyl-formamide; tetrahydrofuran; water / 1 h / 0 - 20 °C
8.1: sodium hydroxide; hydrogen; 5%-palladium/activated carbon / tetrahydrofuran; water; ethanol / 3750.38 Torr
8.2: Dowex resin (Na+ form) |
|
- 31
-
[ 67443-38-3 ]
-
[ 3956-34-1 ]
-
C15H14BrN3O6
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Stage #1: 5-bromo-2-chloro-3-nitropyridine; methyl 4-amino-2,6-dimethoxybenzoate In dimethyl sulfoxide at 80℃; for 0.0833333h;
Stage #2: With triethylamine In dimethyl sulfoxide at 80℃; |
1.2.1.3
To a solution of methyl 4-amino-2,6-dimethoxy-benzoate (232 mg, 1.1 mmol, 1.2 eq.) and 5- bromo-2-chloro-3-nitro-pyridine (250 mg, 0.914 mmol, 1 eq.) in anhydrous DMSO (0.5 mL) stirred to 80 °C for 5 min is added ETN (0.64 mL, 4.57 mmol, 5 eq.). The mixture is stirred to 80 °C then anhydrous DMSO (1 mL) is added and the mixture is stirred to 80 °C overnight. After cooling to RT, the mixture is diluted with EtOAc, water and brine. The aqueous layer is extracted with EtOAC. The combined organic layers are dried, filtered and concentrated in vacuo. The residue is purified by flash chromatography on silica gel (eluting with heptane/EtOAc 80/20) to afford the expected product. |
- 32
-
[ 3956-34-1 ]
-
4-(4-bromo-2-nitroanilino)-N-cyclopropyl-2-(difluoromethoxy)-6-methoxybenzamide
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 7 steps
1.1: boron trichloride / dichloromethane / 0 - 20 °C / Inert atmosphere
2.1: acetic acid / 1.75 h / 20 - 110 °C
3.1: methanol; sodium hydroxide / 18 h / 100 °C
4.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 0.5 h / 20 °C
4.2: 20 °C
5.1: potassium hydroxide / water; acetonitrile / 0.75 h / -15 - -10 °C
6.1: hydroxylamine hydrochloride; triethylamine / ethanol; water / 20 - 110 °C
7.1: sodium hydride / tetrahydrofuran / 0 - 20 °C / Inert atmosphere |
|
- 33
-
[ 3956-34-1 ]
-
2,6-dimethoxy-4-[5-(1-methylimidazol-4-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 5 steps
1.1: lithium hexamethyldisilazane / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere
2.1: tin(II) chloride dihdyrate; tin(ll) chloride / ethanol / 2 h / Reflux
2.2: 2 h / Reflux
3.1: methanol; sodium hydroxide / tetrahydrofuran / 75 °C
4.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 0.17 h / 20 °C
4.2: 20 °C
5.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate / 1,4-dioxane / 100 °C / Inert atmosphere
5.2: 1 h / 90 °C |
|
- 34
-
[ 3956-34-1 ]
-
4-(5-cyanobenzimidazol-1-yl)-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 5 steps
1.1: lithium hexamethyldisilazane / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere
2.1: tin(II) chloride dihdyrate; tin(ll) chloride / ethanol / 2 h / Reflux
2.2: 2 h / Reflux
3.1: methanol; sodium hydroxide / tetrahydrofuran / 75 °C
4.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 0.17 h / 20 °C
4.2: 20 °C
5.1: 1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0); zinc cyanide; zinc / N,N-dimethyl acetamide / 3 h / 125 °C / Inert atmosphere |
|
- 35
-
[ 3956-34-1 ]
-
C19H18F3N5O4
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 6 steps
1.1: lithium hexamethyldisilazane / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere
2.1: tin(II) chloride dihdyrate; tin(ll) chloride / ethanol / 2 h / Reflux
2.2: 2 h / Reflux
3.1: methanol; sodium hydroxide / tetrahydrofuran / 75 °C
4.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 0.17 h / 20 °C
4.2: 20 °C
5.1: 1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0); zinc cyanide; zinc / N,N-dimethyl acetamide / 3 h / 125 °C / Inert atmosphere
6.1: hydroxylamine hydrochloride; triethylamine / ethanol / 5 h / 80 °C |
|
- 36
-
[ 3956-34-1 ]
-
2,6-dimethoxy-4-[5-(5-methyl-1,2,4-oxadiazol-3-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 7 steps
1.1: lithium hexamethyldisilazane / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere
2.1: tin(II) chloride dihdyrate; tin(ll) chloride / ethanol / 2 h / Reflux
2.2: 2 h / Reflux
3.1: methanol; sodium hydroxide / tetrahydrofuran / 75 °C
4.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 0.17 h / 20 °C
4.2: 20 °C
5.1: 1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0); zinc cyanide; zinc / N,N-dimethyl acetamide / 3 h / 125 °C / Inert atmosphere
6.1: hydroxylamine hydrochloride; triethylamine / ethanol / 5 h / 80 °C
7.1: 1 h / 100 °C |
|
- 37
-
[ 3956-34-1 ]
-
4-(4-cyano-2-nitro-anilino)-2-(difluoromethoxy)-N-ethyl-6-methoxy-benzamide
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 7 steps
1.1: boron trichloride / dichloromethane / 0 - 20 °C / Inert atmosphere
2.1: acetic acid / 1.75 h / 20 - 110 °C
3.1: methanol; sodium hydroxide / 18 h / 100 °C
4.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 0.5 h / 20 °C
4.2: 20 °C
5.1: potassium hydroxide / water; acetonitrile / 0.75 h / -15 - -10 °C
6.1: hydroxylamine hydrochloride; triethylamine / ethanol; water / 20 - 110 °C
7.1: sodium hydride / N,N-dimethyl-formamide / 5 h / 0 - 100 °C |
|
- 38
-
[ 3956-34-1 ]
-
2,6-dimethoxy-4-[5-(5-methyl-4H-1,2,4-triazol-3-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 6 steps
1.1: lithium hexamethyldisilazane / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere
2.1: tin(II) chloride dihdyrate; tin(ll) chloride / ethanol / 2 h / Reflux
2.2: 2 h / Reflux
3.1: methanol; sodium hydroxide / tetrahydrofuran / 75 °C
4.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 0.17 h / 20 °C
4.2: 20 °C
5.1: 1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0); zinc cyanide; zinc / N,N-dimethyl acetamide / 3 h / 125 °C / Inert atmosphere
6.1: caesium carbonate; copper(I) bromide / dimethyl sulfoxide / 125 °C |
|
- 39
-
[ 3956-34-1 ]
-
methyl 4-(5-bromobenzimidazol-1-yl)-2,6-dimethoxy-benzoate
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 2 steps
1.1: lithium hexamethyldisilazane / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere
2.1: tin(II) chloride dihdyrate; tin(ll) chloride / ethanol / 2 h / Reflux
2.2: 2 h / Reflux |
|
- 40
-
[ 3956-34-1 ]
-
methyl 4-amino-2-hydroxy-6-methoxybenzoate
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
With boron trichloride In dichloromethane at 0 - 20℃; for 18.75h; Inert atmosphere; |
2.10.1 2.10.1. Step i: methyl 4-amino-2-hydroxy-6-methoxy-benzoate
[0452] To a solution of methyl 4-amino-2,6-dimethoxy-benzoate (CASNo. 3956-34-1; 8.75 g, 41 mmol, 1 eq.) in dry DCM (230 mL) under N2 atmosphere is added BCl3 (1 M in DCM, CASNo. 10294-34-5; 91 mL, 91 mmol, 2.2 eq.) dropwise at 0 °C. The resulting solution is stirred for 45 min and at RT for 18 h. HCl 2 N and ice-water is added and the mixture is extracted twice with DCM. The combined organic layers are washed with water, brine, dried over anhydrous Na2SO4, and concentrated in vacuo to afford the desired intermediate. LCMS: MW (calcd): 197.1; m/z MW (obsd): 198.2 (M+H) |
|
With boron trichloride In dichloromethane at 0 - 20℃; Inert atmosphere; |
2.9.1.i Step i: methyl 4-amino-2-hydroxy-6-methoxy-benzoate
To a solution of methyl 4-amino-2,6-dimethoxy-benzoate (CAS 3956-34-1; 8.75 g, 41 mmol, 1 eq.) in dry DCM (230 mL) under N2 atmosphere is added BCI3 1 M in DCM (91 mL, 91 mmol, 2.2 eq.) dropwise at 0 °C stirred for 45 min and at RT overnight. HC1 2 N and ice-water is added and the mixture is extracted twice with DCM. The combined organic layers are washed with water, brine, dried over anhydrous Na2S04, and evaporated in vacuo to afford the desired product. LCMS: MW (calcd): 197.1; m/z MW (obsd): 198.2 (M+H). |
- 41
-
[ 3956-34-1 ]
-
methyl 4-(2,5-dimethylpyrrol-1-yl)-2-hydroxy-6-methoxybenzoate
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 2 steps
1: boron trichloride / dichloromethane / 18.75 h / 0 - 20 °C / Inert atmosphere
2: acetic acid / 1.75 h / 20 - 110 °C |
|
|
Multi-step reaction with 2 steps
1: boron trichloride / dichloromethane / 0 - 20 °C / Inert atmosphere
2: acetic acid / 1.75 h / 20 - 110 °C |
|
- 42
-
[ 3956-34-1 ]
-
4-(2,5-dimethylpyrrol-1-yl)-2-hydroxy-6-methoxybenzoic acid
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 3 steps
1: boron trichloride / dichloromethane / 18.75 h / 0 - 20 °C / Inert atmosphere
2: acetic acid / 1.75 h / 20 - 110 °C
3: sodium hydroxide; methanol / 18 h / 100 °C |
|
|
Multi-step reaction with 3 steps
1: boron trichloride / dichloromethane / 0 - 20 °C / Inert atmosphere
2: acetic acid / 1.75 h / 20 - 110 °C
3: methanol; sodium hydroxide / 18 h / 100 °C |
|
- 43
-
[ 3956-34-1 ]
-
N-cyclopropyl-4-(2,5-dimethylpyrrol-1-yl)-2-hydroxy-6-methoxybenzamide
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 4 steps
1.1: boron trichloride / dichloromethane / 18.75 h / 0 - 20 °C / Inert atmosphere
2.1: acetic acid / 1.75 h / 20 - 110 °C
3.1: sodium hydroxide; methanol / 18 h / 100 °C
4.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 0.17 h / 20 °C
4.2: 2 h / 20 °C |
|
|
Multi-step reaction with 4 steps
1.1: boron trichloride / dichloromethane / 0 - 20 °C / Inert atmosphere
2.1: acetic acid / 1.75 h / 20 - 110 °C
3.1: methanol; sodium hydroxide / 18 h / 100 °C
4.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 0.17 h / 20 °C
4.2: 2 h / 20 °C |
|
- 44
-
[ 3956-34-1 ]
-
N-cyclopropyl-2-(difluoromethoxy)-4-(2,5-dimethylpyrrol-1-yl)-6-methoxy-benzamide
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 5 steps
1.1: boron trichloride / dichloromethane / 18.75 h / 0 - 20 °C / Inert atmosphere
2.1: acetic acid / 1.75 h / 20 - 110 °C
3.1: sodium hydroxide; methanol / 18 h / 100 °C
4.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 0.17 h / 20 °C
4.2: 2 h / 20 °C
5.1: potassium hydroxide / acetonitrile; water / 0.42 h / -10 °C |
|
|
Multi-step reaction with 5 steps
1.1: boron trichloride / dichloromethane / 0 - 20 °C / Inert atmosphere
2.1: acetic acid / 1.75 h / 20 - 110 °C
3.1: methanol; sodium hydroxide / 18 h / 100 °C
4.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 0.17 h / 20 °C
4.2: 2 h / 20 °C
5.1: potassium hydroxide / water; acetonitrile / 0.42 h / -10 °C |
|
- 45
-
[ 3956-34-1 ]
-
4-amino-N-cyclopropyl-2-(difluoromethoxy)-6-methoxy-benzamide
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 6 steps
1.1: boron trichloride / dichloromethane / 18.75 h / 0 - 20 °C / Inert atmosphere
2.1: acetic acid / 1.75 h / 20 - 110 °C
3.1: sodium hydroxide; methanol / 18 h / 100 °C
4.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 0.17 h / 20 °C
4.2: 2 h / 20 °C
5.1: potassium hydroxide / acetonitrile; water / 0.42 h / -10 °C
6.1: triethylamine; hydroxylamine hydrochloride / water; ethanol / 18 h / 110 °C
6.2: 3.5 h / 110 °C |
|
|
Multi-step reaction with 6 steps
1.1: boron trichloride / dichloromethane / 0 - 20 °C / Inert atmosphere
2.1: acetic acid / 1.75 h / 20 - 110 °C
3.1: methanol; sodium hydroxide / 18 h / 100 °C
4.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 0.17 h / 20 °C
4.2: 2 h / 20 °C
5.1: potassium hydroxide / water; acetonitrile / 0.42 h / -10 °C
6.1: hydroxylamine hydrochloride / ethanol; water / 20 - 110 °C
6.2: 3.5 h / 110 °C |
|
- 46
-
[ 3956-34-1 ]
-
N-tert-butyl-4-(2,5-dimethylpyrrol-1-yl)-2-hydroxy-6-methoxybenzamide
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 4 steps
1: boron trichloride / dichloromethane / 0 - 20 °C / Inert atmosphere
2: acetic acid / 1.75 h / 20 - 110 °C
3: methanol; sodium hydroxide / 18 h / 100 °C
4: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 0.17 h / 20 °C |
|
- 47
-
[ 3956-34-1 ]
-
N-tert-butyl-2-(difluoromethoxy)-4-(2,5-dimethylpyrrol-1-yl)-6-methoxybenzamide
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 5 steps
1.1: boron trichloride / dichloromethane / 0 - 20 °C / Inert atmosphere
2.1: acetic acid / 1.75 h / 20 - 110 °C
3.1: methanol; sodium hydroxide / 18 h / 100 °C
4.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 0.17 h / 20 °C
5.1: potassium hydroxide / water; acetonitrile / 0.17 h / -10 °C
5.2: 0.5 h / 0 °C |
|
- 48
-
[ 3956-34-1 ]
-
[ 364-73-8 ]
-
methyl 4-(4-bromo-2-nitroanilino)-2,6-dimethoxybenzoate
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
With lithium hexamethyldisilazane In tetrahydrofuran at 0℃; for 2h; Inert atmosphere; |
1.2.15 Illustrative synthesis of Int 29
[0374] A solution of methyl 4-amino-2,6-dimethoxy-benzoate (40 g, 189.4 mmol, 1 eq.) and 4-bromo-1- fluoro-2-nitro-benzene (23.3 mL, 189.4 mmol, 1 eq.) in THF (1 L) is cooled at 0 °C under N2. LiHMDS (1M solution in THF, 435.6 mL, 435.6 mmol, 2.3 eq.) is then added dropwise over 2 h. The reaction is quenched with water (800 mL). THF is evaporated, and the rest of the reaction mixture is left stirred at 3 °C for 18 h. To the reaction mixture 2 M HCl (600 mL) is added slowly while rapidly stirred and the mixture is stirred for 1 h at 3 °C. The precipitate is filtered off then dried in a vacuum oven at 45 °C and 20 mbar for 5 h to afford the desired compound. |
|
With lithium hexamethyldisilazane In tetrahydrofuran at 0℃; for 2h; Inert atmosphere; |
1.2.1.1 1.2.1.1. Method Bl: SNAV of disubstituted amino benzoate on halogeno nitro phenyl derivative
A solution of methyl 4-amino-2,6-dimethoxy-benzoate (1 eq.) and 4-bromo-l-fluoro-2-nitro- benzene (1 eq.) in THF is cooled at 0 °C under N2. LiHMDS (1 M solution in THF, 2.3 eq.) is then added dropwise over 2 h. The reaction is quenched with water. THF is evaporated, and the rest of the reaction mixture is left stirred at 3 °C overnight. To the reaction mixture 2 M HC1 is added slowly while rapidly stirred and the mixture is stirred for 1 h at 3 °C. The precipitate is filtered off then dried in a vacuum oven at 45 °C and 20 mbar for 5 h to afford the expected intermediate. |
- 49
-
[ 3956-34-1 ]
-
[ 81574-70-1 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Stage #1: methyl 4-amino-2,6-dimethoxybenzoate With sulfuric acid; sodium nitrite In water; acetonitrile at 0℃; for 0.5h;
Stage #2: With copper(I) bromide In water; acetonitrile at 20℃; for 18h; |
2.7 2.7. Int 21
[0449] To a solution of methyl 4-amino-2,6-dimethoxybenzoate (CASNo. 3956-34-1; 8 g, 38 mmol, 1 eq.) in ACN (160 mL) at 0 °C is added carefully H2SO4 (8 mL, 151 mmol, 4 eq.) in water (17 mL). Then a solution of sodium nitrite (CASNo. 7632-00-0; 2.7 g, 39 mmol, 1.02 eq.) in water (16 mL) is added dropwise. A precipitate is formed.The resulting mixture is stirred at 0 °C for 30 min. Then CuBr (CASNo. 7789-45-9; 20.4 g, 142 mmol, 3.75 eq.) is introduced by portions. The resulting suspension is stirred at RT for 18 h, filtered on celite. The solid is washed with DCM (300 mL). The filtrate is washed with water and brine. The combined organic layers are dried over MgSO4, filtered and concentrated in vacuo. The residue is purified by flash chromatography on silica gel (eluting with heptane/EtOAc 98/2 to 70/30) to afford the desired intermediate. |
- 50
-
[ 3956-34-1 ]
-
1-(4-fluoro-3-nitrophenyl)cyclobutane-1-carbonitrile
[ No CAS ]
-
methyl 4-[4-(1-cyanocyclobutyl)-2-nitro-aniline]-2,6-dimethoxy-benzoate
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
With sodium hydride In tetrahydrofuran at 0 - 20℃; for 18.1667h; Inert atmosphere; |
1.2.16 1.2.16. Method F2: SNAr of disubstituted amino benzamide or benzoate on halogeno nitro phenyl derivative with NaH
General procedure: [0375] To a solution of disubstituted amino benzamide or methyl 4-amino-2,6-disubstituted-benzoate (1 to 1.1 eq.) in anhydrous THF, placed under argon atmosphere is added fluoro nitro derivative (1 to 1.7 eq.). The mixture is cooled at 0 °C and NaH (CAS 7646-69-7; 3 eq.) is added portionwise. The mixture is stirred at 0 °C for 10 min then at RT for 18 h. The mixture is cooled to 0 °C, quenched with water or a sat. NH4Cl solution, diluted with EtOAc or DCM and water, a sat. NH4Cl solution or brine, extracted with EtOAc or DCM. The combined organic layers are dried or washed with brine then dried (Na2SO4 or MgSO4), filtered and concentrated in vacuo. Purification by flash chromatography on silica gel affords the desired compound. |
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