Alternatived Products of [ 33797-36-3 ]
Product Details of [ 33797-36-3 ]
| CAS No. : | 33797-36-3 |
MDL No. : | MFCD18398342 |
| Formula : |
C10H12O3
|
Boiling Point : |
- |
| Linear Structure Formula : | - |
InChI Key : | VITXJZAFITXKJF-UHFFFAOYSA-N |
| M.W : |
180.20
|
Pubchem ID : | 20474313 |
| Synonyms : |
|
Application In Synthesis of [ 33797-36-3 ]
* 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 [ 33797-36-3 ]
- 1
-
[ 33797-35-2 ]
-
[ 33797-36-3 ]
| Yield | Reaction Conditions | Operation in experiment |
| 97% |
Stage #1: 2-(3-methoxy-2-methylphenyl)acetonitrile With sodium hydroxide In ethanol; water for 48h; Reflux;
Stage #2: With hydrogenchloride In water |
|
| 86% |
With potassium hydroxide In ethanol for 5h; Reflux; Large scale; |
25 Example 25 Preparation of intermediate 7-Bromomethyl-6-methyl-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid tert-butyl ester (D-11)
A mixture of D-3-3 (1608 g, 9.975 mol) and KOH (1117 g, 19.95 mol) in EtOH_ (15 L) is heated to reflux for 5 h. The solvent is removed under reduced pressure. The pH of the residue is adjusted to pH 1. The mixture is filtered and the filter cake is dried to yield D-11-1 (1474 g, 86% yield). |
|
With potassium hydroxide In ethanol |
|
Reference：
[1]Taylor, Simon J.; Demont, Emmanuel H.; Gray, James; Deeks, Nigel; Patel, Aarti; Nguyen, Dung; Taylor, Maxine; Hood, Steve; Watson, Robert J.; Bit, Rino A.; McClure, Fiona; Ashall, Holly; Witherington, Jason
[Journal of Medicinal Chemistry, 2015, vol. 58, # 20, p. 8236 - 8256]
[2]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/24059, 2016, A1
Location in patent: Paragraph 0401-0402
[3]Mukharji,P.C. et al.
[Indian Journal of Chemistry, 1971, vol. 9, p. 515 - 523]
- 2
-
[ 33797-36-3 ]
-
[ 23985-50-4 ]
| Yield | Reaction Conditions | Operation in experiment |
| 70% |
With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 23℃; for 1h; Inert atmosphere; |
|
|
With lithium aluminium tetrahydride 1.) esterification; Yield given. Multistep reaction; |
|
Reference：
[1]Alvarado, Joseph; Fournier, Jeremy; Zakarian, Armen
[Angewandte Chemie - International Edition, 2016, vol. 55, # 38, p. 11625 - 11628][Angew. Chem., 2016, vol. 128, p. 11797 - 11800]
[2]Cossey, Ailsa L.; Gunter, Maxwell J.; Mander, Lewis N.
[Tetrahedron Letters, 1980, vol. 21, # 34, p. 3309 - 3312]
- 3
-
[ 76640-59-0 ]
-
[ 33797-36-3 ]
| Yield | Reaction Conditions | Operation in experiment |
| 100% |
With sodium hydroxide In methanol for 18h; Heating; |
|
|
With sodium hydroxide In ethanol; water at 90℃; for 48h; Inert atmosphere; |
|
Reference：
[1]Cossey, Ailsa L.; Gunter, Maxwell J.; Mander, Lewis N.
[Tetrahedron Letters, 1980, vol. 21, # 34, p. 3309 - 3312]
[2]Alvarado, Joseph; Fournier, Jeremy; Zakarian, Armen
[Angewandte Chemie - International Edition, 2016, vol. 55, # 38, p. 11625 - 11628][Angew. Chem., 2016, vol. 128, p. 11797 - 11800]
- 4
-
[ 612-16-8 ]
-
[ 33797-36-3 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 2 steps
1: 40 percent / dichlorobenzene / 40 h / Heating
2: 100 percent / 10percent aq. NaOH / methanol / 18 h / Heating |
|
|
Multi-step reaction with 2 steps
1: toluene / 14 h / 170 °C / Microwave irradiation; Inert atmosphere
2: sodium hydroxide / water; ethanol / 48 h / 90 °C / Inert atmosphere |
|
Reference：
[1]Cossey, Ailsa L.; Gunter, Maxwell J.; Mander, Lewis N.
[Tetrahedron Letters, 1980, vol. 21, # 34, p. 3309 - 3312]
[2]Alvarado, Joseph; Fournier, Jeremy; Zakarian, Armen
[Angewandte Chemie - International Edition, 2016, vol. 55, # 38, p. 11625 - 11628][Angew. Chem., 2016, vol. 128, p. 11797 - 11800]
- 5
-
[ 33797-36-3 ]
-
[ 76640-45-4 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 2 steps
1: 2.) LiAlH4 / 1.) esterification
2: 1.) p-toluene sulfonyl chloride, pyridine, 2.) NaI. / 2.) acetone |
|
- 6
-
[ 33797-36-3 ]
-
2-hydroxy-1,7-dimethyl-5-vinyl-9,10-dihydrophenanthrene
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 9 steps
1: 2.) LiAlH4 / 1.) esterification
2: 1.) p-toluene sulfonyl chloride, pyridine, 2.) NaI. / 2.) acetone
3: lithium diisopropylamide / 1.) THF, -78 deg C, 0.5 h; 2.) HMPA, from -78 deg C to 25 deg C, 16 h
4: 95 percent / BF3*Et2O / CH2Cl2 / 0.25 h / 24 °C
5: 94 percent / POCl3 / dimethylformamide / 20 h / 70 °C
6: 89 percent / n-BuLi / tetrahydrofuran / 0.08 h / 22 °C
7: 85 percent / 3M NaOH / ethanol / 8 h / Heating
8: 92 percent / Pb(OAc)4, Cu(OAc)2 / benzene / 0.08 h / 80 °C
9: lithium thiomethoxide / hexamethylphosphoric acid triamide / 2 h / 180 °C |
|
- 7
-
[ 33797-36-3 ]
-
[ 76640-58-9 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 8 steps
1: 2.) LiAlH4 / 1.) esterification
2: 1.) p-toluene sulfonyl chloride, pyridine, 2.) NaI. / 2.) acetone
3: lithium diisopropylamide / 1.) THF, -78 deg C, 0.5 h; 2.) HMPA, from -78 deg C to 25 deg C, 16 h
4: 95 percent / BF3*Et2O / CH2Cl2 / 0.25 h / 24 °C
5: 94 percent / POCl3 / dimethylformamide / 20 h / 70 °C
6: 89 percent / n-BuLi / tetrahydrofuran / 0.08 h / 22 °C
7: 85 percent / 3M NaOH / ethanol / 8 h / Heating
8: 92 percent / Pb(OAc)4, Cu(OAc)2 / benzene / 0.08 h / 80 °C |
|
- 8
-
[ 33797-36-3 ]
-
[ 76640-55-6 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 4 steps
1: 2.) LiAlH4 / 1.) esterification
2: 1.) p-toluene sulfonyl chloride, pyridine, 2.) NaI. / 2.) acetone
3: lithium diisopropylamide / 1.) THF, -78 deg C, 0.5 h; 2.) HMPA, from -78 deg C to 25 deg C, 16 h
4: 95 percent / BF3*Et2O / CH2Cl2 / 0.25 h / 24 °C |
|
- 9
-
[ 33797-36-3 ]
-
[ 76640-54-5 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 3 steps
1: 2.) LiAlH4 / 1.) esterification
2: 1.) p-toluene sulfonyl chloride, pyridine, 2.) NaI. / 2.) acetone
3: lithium diisopropylamide / 1.) THF, -78 deg C, 0.5 h; 2.) HMPA, from -78 deg C to 25 deg C, 16 h |
|
- 10
-
[ 33797-36-3 ]
-
[ 76640-57-8 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 7 steps
1: 2.) LiAlH4 / 1.) esterification
2: 1.) p-toluene sulfonyl chloride, pyridine, 2.) NaI. / 2.) acetone
3: lithium diisopropylamide / 1.) THF, -78 deg C, 0.5 h; 2.) HMPA, from -78 deg C to 25 deg C, 16 h
4: 95 percent / BF3*Et2O / CH2Cl2 / 0.25 h / 24 °C
5: 94 percent / POCl3 / dimethylformamide / 20 h / 70 °C
6: 89 percent / n-BuLi / tetrahydrofuran / 0.08 h / 22 °C
7: 85 percent / 3M NaOH / ethanol / 8 h / Heating |
|
- 11
-
[ 33797-36-3 ]
-
[ 76640-56-7 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 6 steps
1: 2.) LiAlH4 / 1.) esterification
2: 1.) p-toluene sulfonyl chloride, pyridine, 2.) NaI. / 2.) acetone
3: lithium diisopropylamide / 1.) THF, -78 deg C, 0.5 h; 2.) HMPA, from -78 deg C to 25 deg C, 16 h
4: 95 percent / BF3*Et2O / CH2Cl2 / 0.25 h / 24 °C
5: 94 percent / POCl3 / dimethylformamide / 20 h / 70 °C
6: 89 percent / n-BuLi / tetrahydrofuran / 0.08 h / 22 °C |
|
- 12
-
[ 33797-36-3 ]
-
[ 76656-97-8 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 5 steps
1: 2.) LiAlH4 / 1.) esterification
2: 1.) p-toluene sulfonyl chloride, pyridine, 2.) NaI. / 2.) acetone
3: lithium diisopropylamide / 1.) THF, -78 deg C, 0.5 h; 2.) HMPA, from -78 deg C to 25 deg C, 16 h
4: 95 percent / BF3*Et2O / CH2Cl2 / 0.25 h / 24 °C
5: 94 percent / POCl3 / dimethylformamide / 20 h / 70 °C |
|
- 13
-
[ 33797-36-3 ]
-
[ 76640-46-5 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 3 steps
1: 2.) LiAlH4 / 1.) esterification
2: 1.) p-toluene sulfonyl chloride, pyridine, 2.) NaI. / 2.) acetone
3: 1.) lithium-ammonia |
|
- 14
-
[ 33797-34-1 ]
-
[ 33797-36-3 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 3 steps
1: PCl3 / benzene
2: aq. NaI
3: aq. KOH / ethanol |
|
|
Multi-step reaction with 3 steps
1.1: methanesulfonyl chloride; triethylamine / dichloromethane / 2 h / 0 - 20 °C
2.1: N,N-dimethyl-formamide / 96 h / 90 °C
3.1: sodium hydroxide / ethanol; water / 48 h / Reflux
3.2: pH 2 |
|
|
Multi-step reaction with 3 steps
1: thionyl chloride / dichloromethane / 1 h / -10 °C / Reflux
2: N,N-dimethyl-formamide / 12 h / 20 °C
3: potassium hydroxide / ethanol / 5 h / Reflux; Large scale |
|
Reference：
[1]Mukharji,P.C. et al.
[Indian Journal of Chemistry, 1971, vol. 9, p. 515 - 523]
[2]Taylor, Simon J.; Demont, Emmanuel H.; Gray, James; Deeks, Nigel; Patel, Aarti; Nguyen, Dung; Taylor, Maxine; Hood, Steve; Watson, Robert J.; Bit, Rino A.; McClure, Fiona; Ashall, Holly; Witherington, Jason
[Journal of Medicinal Chemistry, 2015, vol. 58, # 20, p. 8236 - 8256]
[3]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/24059, 2016, A1
- 15
-
[ 42981-94-2 ]
-
[ 33797-36-3 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 2 steps
1: aq. NaI
2: aq. KOH / ethanol |
|
|
Multi-step reaction with 2 steps
1.1: N,N-dimethyl-formamide / 96 h / 90 °C
2.1: sodium hydroxide / ethanol; water / 48 h / Reflux
2.2: pH 2 |
|
|
Multi-step reaction with 2 steps
1: N,N-dimethyl-formamide / 12 h / 20 °C
2: potassium hydroxide / ethanol / 5 h / Reflux; Large scale |
|
Reference：
[1]Mukharji,P.C. et al.
[Indian Journal of Chemistry, 1971, vol. 9, p. 515 - 523]
[2]Taylor, Simon J.; Demont, Emmanuel H.; Gray, James; Deeks, Nigel; Patel, Aarti; Nguyen, Dung; Taylor, Maxine; Hood, Steve; Watson, Robert J.; Bit, Rino A.; McClure, Fiona; Ashall, Holly; Witherington, Jason
[Journal of Medicinal Chemistry, 2015, vol. 58, # 20, p. 8236 - 8256]
[3]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/24059, 2016, A1
- 16
-
[ 627883-78-7 ]
-
[ 33797-36-3 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 4 steps
1: LiAlH4
2: PCl3 / benzene
3: aq. NaI
4: aq. KOH / ethanol |
|
- 17
-
[ 33797-36-3 ]
-
C10H11ClO2
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
With oxalyl dichloride In dichloromethane at 20℃; for 3h; |
60
Preparation 60: N-(2,2-Dimethoxy-ethyl)-2-(3-methoxy-2-methyl-phenyl)-acetamide; To a stirred solution of (3-methoxy-2-methyl-phenyl) -acetic acid (18.2 g, Tetrahedron Letters, 1980, Vol.21 , 3309-3312) in DCM (500 ml) and DMF (5 ml) at room temperature, oxalyl dichloride (19.7 ml) was added dropwise. After 3 hours volatiles were evaporated under reduced pressure, the residue was dissolved in DCM (100 ml) and added dropwise to a stirred solution of 2,2-dimethoxy- ethylamine (10.67 g, 1 eq) and triethylamine (16 ml, 1.1 eq) in DCM (400 ml) at room temperature. After 24 hours the mixture was washed with water, 10% acetic acid, sat. NaHC03 and brine. The organic phase was dried (Na2S04) and concentrated to afford 25 g of desired product (92% yield). MS (m/z): 268 [MH]+. |
|
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 2h; |
|
Reference：
[1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2005/118549, 2005, A2
Location in patent: Page/Page column 41-42
[2]Taylor, Simon J.; Demont, Emmanuel H.; Gray, James; Deeks, Nigel; Patel, Aarti; Nguyen, Dung; Taylor, Maxine; Hood, Steve; Watson, Robert J.; Bit, Rino A.; McClure, Fiona; Ashall, Holly; Witherington, Jason
[Journal of Medicinal Chemistry, 2015, vol. 58, # 20, p. 8236 - 8256]
- 18
-
[ 56724-03-9 ]
-
[ 33797-36-3 ]
- 19
-
[ 591-31-1 ]
-
[ 33797-36-3 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 3 steps
1.1: n-butyllithium; N,N',N'-trimethylenediamine / tetrahydrofuran / -20 °C / Inert atmosphere
1.2: 10 h / -40 °C / Inert atmosphere
1.3: Inert atmosphere
2.1: potassium hydroxide / methanol; N,N-dimethyl-formamide / 2 h / -10 °C / Inert atmosphere
2.2: 0.5 h / -10 °C / Inert atmosphere
3.1: sodium hydroxide; sodium tetrahydroborate; diphenyl diselenide / ethanol / 20 - 40 °C / Inert atmosphere |
|
Reference：
[1]Resch, Verena; Lechner, Horst; Schrittwieser, Joerg H.; Wallner, Silvia; Gruber, Karl; MacHeroux, Peter; Kroutil, Wolfgang
[Chemistry - A European Journal, 2012, vol. 18, # 41, p. 13173 - 13179]
- 20
-
[ 1418126-54-1 ]
-
[ 33797-36-3 ]
| Yield | Reaction Conditions | Operation in experiment |
| 3.3 g |
With sodium tetrahydroborate; diphenyl diselenide; sodium hydroxide In ethanol at 20 - 40℃; Inert atmosphere; |
|
Reference：
[1]Resch, Verena; Lechner, Horst; Schrittwieser, Joerg H.; Wallner, Silvia; Gruber, Karl; MacHeroux, Peter; Kroutil, Wolfgang
[Chemistry - A European Journal, 2012, vol. 18, # 41, p. 13173 - 13179]
- 21
-
[ 33797-36-3 ]
-
[ 1418126-23-4 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 6 steps
1.1: bromic acid / water / 5 h / 105 °C
2.1: sodium iodide; potassium hydroxide / ethanol / 20 °C
3.1: oxalyl dichloride; N,N-dimethyl-formamide / toluene / 3 h
4.1: sodium hydroxide / chloroform; water / 16 h / 20 °C / Cooling with ice
5.1: trichlorophosphate / acetonitrile / 3 h / Inert atmosphere; Reflux
5.2: 16 h / 20 °C / Inert atmosphere; Cooling with ice
6.1: acetic acid; hydrogen; palladium on activated charcoal / methanol / 16 h / 760.05 Torr |
|
Reference：
[1]Resch, Verena; Lechner, Horst; Schrittwieser, Joerg H.; Wallner, Silvia; Gruber, Karl; MacHeroux, Peter; Kroutil, Wolfgang
[Chemistry - A European Journal, 2012, vol. 18, # 41, p. 13173 - 13179]
- 22
-
[ 33797-36-3 ]
-
[ 1261616-79-8 ]
| Yield | Reaction Conditions | Operation in experiment |
|
With bromic acid In water at 105℃; for 5h; |
|
Reference：
[1]Resch, Verena; Lechner, Horst; Schrittwieser, Joerg H.; Wallner, Silvia; Gruber, Karl; MacHeroux, Peter; Kroutil, Wolfgang
[Chemistry - A European Journal, 2012, vol. 18, # 41, p. 13173 - 13179]
- 23
-
[ 33797-36-3 ]
-
[ 1418126-55-2 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 2 steps
1: bromic acid / water / 5 h / 105 °C
2: sodium iodide; potassium hydroxide / ethanol / 20 °C |
|
Reference：
[1]Resch, Verena; Lechner, Horst; Schrittwieser, Joerg H.; Wallner, Silvia; Gruber, Karl; MacHeroux, Peter; Kroutil, Wolfgang
[Chemistry - A European Journal, 2012, vol. 18, # 41, p. 13173 - 13179]
- 24
-
[ 33797-36-3 ]
-
[ 1418126-56-3 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 3 steps
1: bromic acid / water / 5 h / 105 °C
2: sodium iodide; potassium hydroxide / ethanol / 20 °C
3: oxalyl dichloride; N,N-dimethyl-formamide / toluene / 3 h |
|
Reference：
[1]Resch, Verena; Lechner, Horst; Schrittwieser, Joerg H.; Wallner, Silvia; Gruber, Karl; MacHeroux, Peter; Kroutil, Wolfgang
[Chemistry - A European Journal, 2012, vol. 18, # 41, p. 13173 - 13179]
- 25
-
[ 33797-36-3 ]
-
[ 1418126-57-4 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 4 steps
1: bromic acid / water / 5 h / 105 °C
2: sodium iodide; potassium hydroxide / ethanol / 20 °C
3: oxalyl dichloride; N,N-dimethyl-formamide / toluene / 3 h
4: sodium hydroxide / chloroform; water / 16 h / 20 °C / Cooling with ice |
|
Reference：
[1]Resch, Verena; Lechner, Horst; Schrittwieser, Joerg H.; Wallner, Silvia; Gruber, Karl; MacHeroux, Peter; Kroutil, Wolfgang
[Chemistry - A European Journal, 2012, vol. 18, # 41, p. 13173 - 13179]
- 26
-
[ 33797-36-3 ]
-
[ 1418126-59-6 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 5 steps
1.1: bromic acid / water / 5 h / 105 °C
2.1: sodium iodide; potassium hydroxide / ethanol / 20 °C
3.1: oxalyl dichloride; N,N-dimethyl-formamide / toluene / 3 h
4.1: sodium hydroxide / chloroform; water / 16 h / 20 °C / Cooling with ice
5.1: trichlorophosphate / acetonitrile / 3 h / Inert atmosphere; Reflux
5.2: 16 h / 20 °C / Inert atmosphere; Cooling with ice |
|
Reference：
[1]Resch, Verena; Lechner, Horst; Schrittwieser, Joerg H.; Wallner, Silvia; Gruber, Karl; MacHeroux, Peter; Kroutil, Wolfgang
[Chemistry - A European Journal, 2012, vol. 18, # 41, p. 13173 - 13179]
- 27
-
[ 33797-36-3 ]
-
[ 871501-25-6 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 2 steps
1.1: oxalyl dichloride / dichloromethane; N,N-dimethyl-formamide / 2 h / Inert atmosphere
1.2: 2 h / 20 °C
2.1: acetic acid; hydrogenchloride / 16 h / 20 °C |
|
|
Multi-step reaction with 3 steps
1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 2 h / 20 °C
2: triethylamine / dichloromethane / 1 h / 20 °C
3: acetic acid; hydrogenchloride / water / 3 h / 20 °C |
|
|
Multi-step reaction with 2 steps
1.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 2 h / 20 °C / Large scale
1.2: 2 h / 20 °C / Large scale
2.1: hydrogenchloride; acetic acid / water / 16 h / 20 °C / Large scale |
|
Reference：
[1]Current Patent Assignee: CORTEVA INC; C.H. Boehringer Sohn AG & Co. KG; F.LLI GANCIA & C. SPA - US2014/73629, 2014, A1
[2]Taylor, Simon J.; Demont, Emmanuel H.; Gray, James; Deeks, Nigel; Patel, Aarti; Nguyen, Dung; Taylor, Maxine; Hood, Steve; Watson, Robert J.; Bit, Rino A.; McClure, Fiona; Ashall, Holly; Witherington, Jason
[Journal of Medicinal Chemistry, 2015, vol. 58, # 20, p. 8236 - 8256]
[3]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/24059, 2016, A1
- 28
-
[ 33797-36-3 ]
-
[ 871501-26-7 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 3 steps
1.1: oxalyl dichloride / dichloromethane; N,N-dimethyl-formamide / 2 h / Inert atmosphere
1.2: 2 h / 20 °C
2.1: acetic acid; hydrogenchloride / 16 h / 20 °C
3.1: hydrogen; palladium on activated charcoal / acetic acid / 16 h / 20 °C / 2585.81 Torr |
|
|
Multi-step reaction with 4 steps
1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 2 h / 20 °C
2: triethylamine / dichloromethane / 1 h / 20 °C
3: acetic acid; hydrogenchloride / water / 3 h / 20 °C
4: hydrogen; palladium 10% on activated carbon / methanol / 16 h |
|
|
Multi-step reaction with 3 steps
1.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 2 h / 20 °C / Large scale
1.2: 2 h / 20 °C / Large scale
2.1: hydrogenchloride; acetic acid / water / 16 h / 20 °C / Large scale
3.1: hydrogen; acetic acid; palladium on activated charcoal / 16 h / 20 °C |
|
Reference：
[1]Current Patent Assignee: CORTEVA INC; C.H. Boehringer Sohn AG & Co. KG; F.LLI GANCIA & C. SPA - US2014/73629, 2014, A1
[2]Taylor, Simon J.; Demont, Emmanuel H.; Gray, James; Deeks, Nigel; Patel, Aarti; Nguyen, Dung; Taylor, Maxine; Hood, Steve; Watson, Robert J.; Bit, Rino A.; McClure, Fiona; Ashall, Holly; Witherington, Jason
[Journal of Medicinal Chemistry, 2015, vol. 58, # 20, p. 8236 - 8256]
[3]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/24059, 2016, A1
- 29
-
[ 33797-36-3 ]
-
[ 871501-27-8 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 4 steps
1.1: oxalyl dichloride / dichloromethane; N,N-dimethyl-formamide / 2 h / Inert atmosphere
1.2: 2 h / 20 °C
2.1: acetic acid; hydrogenchloride / 16 h / 20 °C
3.1: hydrogen; palladium on activated charcoal / acetic acid / 16 h / 20 °C / 2585.81 Torr
4.1: dimethylsulfide borane complex / tetrahydrofuran / 16 h / -5 °C / Inert atmosphere |
|
|
Multi-step reaction with 5 steps
1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 2 h / 20 °C
2: triethylamine / dichloromethane / 1 h / 20 °C
3: acetic acid; hydrogenchloride / water / 3 h / 20 °C
4: hydrogen; palladium 10% on activated carbon / methanol / 16 h
5: borane-THF / tetrahydrofuran / 16 h / 60 °C / Inert atmosphere |
|
|
Multi-step reaction with 4 steps
1.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 2 h / 20 °C / Large scale
1.2: 2 h / 20 °C / Large scale
2.1: hydrogenchloride; acetic acid / water / 16 h / 20 °C / Large scale
3.1: hydrogen; acetic acid; palladium on activated charcoal / 16 h / 20 °C
4.1: dimethylsulfide borane complex / tetrahydrofuran / 16 h / -5 °C / Inert atmosphere
4.2: 2 h / Reflux |
|
Reference：
[1]Current Patent Assignee: CORTEVA INC; C.H. Boehringer Sohn AG & Co. KG; F.LLI GANCIA & C. SPA - US2014/73629, 2014, A1
[2]Taylor, Simon J.; Demont, Emmanuel H.; Gray, James; Deeks, Nigel; Patel, Aarti; Nguyen, Dung; Taylor, Maxine; Hood, Steve; Watson, Robert J.; Bit, Rino A.; McClure, Fiona; Ashall, Holly; Witherington, Jason
[Journal of Medicinal Chemistry, 2015, vol. 58, # 20, p. 8236 - 8256]
[3]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/24059, 2016, A1
- 30
-
[ 33797-36-3 ]
-
[ 871542-25-5 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 5 steps
1.1: oxalyl dichloride / dichloromethane; N,N-dimethyl-formamide / 2 h / Inert atmosphere
1.2: 2 h / 20 °C
2.1: acetic acid; hydrogenchloride / 16 h / 20 °C
3.1: hydrogen; palladium on activated charcoal / acetic acid / 16 h / 20 °C / 2585.81 Torr
4.1: dimethylsulfide borane complex / tetrahydrofuran / 16 h / -5 °C / Inert atmosphere
5.1: hydrogen bromide / water / 4 h / 110 °C / Inert atmosphere |
|
|
Multi-step reaction with 6 steps
1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 2 h / 20 °C
2: triethylamine / dichloromethane / 1 h / 20 °C
3: acetic acid; hydrogenchloride / water / 3 h / 20 °C
4: hydrogen; palladium 10% on activated carbon / methanol / 16 h
5: borane-THF / tetrahydrofuran / 16 h / 60 °C / Inert atmosphere
6: hydrogen bromide / water / 3 h / 100 °C |
|
|
Multi-step reaction with 5 steps
1.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 2 h / 20 °C / Large scale
1.2: 2 h / 20 °C / Large scale
2.1: hydrogenchloride; acetic acid / water / 16 h / 20 °C / Large scale
3.1: hydrogen; acetic acid; palladium on activated charcoal / 16 h / 20 °C
4.1: dimethylsulfide borane complex / tetrahydrofuran / 16 h / -5 °C / Inert atmosphere
4.2: 2 h / Reflux
5.1: hydrogen bromide / water / 4 h / 110 °C / Inert atmosphere |
|
Reference：
[1]Current Patent Assignee: CORTEVA INC; C.H. Boehringer Sohn AG & Co. KG; F.LLI GANCIA & C. SPA - US2014/73629, 2014, A1
[2]Taylor, Simon J.; Demont, Emmanuel H.; Gray, James; Deeks, Nigel; Patel, Aarti; Nguyen, Dung; Taylor, Maxine; Hood, Steve; Watson, Robert J.; Bit, Rino A.; McClure, Fiona; Ashall, Holly; Witherington, Jason
[Journal of Medicinal Chemistry, 2015, vol. 58, # 20, p. 8236 - 8256]
[3]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/24059, 2016, A1
- 31
-
[ 33797-36-3 ]
-
[ 871501-28-9 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 6 steps
1.1: oxalyl dichloride / dichloromethane; N,N-dimethyl-formamide / 2 h / Inert atmosphere
1.2: 2 h / 20 °C
2.1: acetic acid; hydrogenchloride / 16 h / 20 °C
3.1: hydrogen; palladium on activated charcoal / acetic acid / 16 h / 20 °C / 2585.81 Torr
4.1: dimethylsulfide borane complex / tetrahydrofuran / 16 h / -5 °C / Inert atmosphere
5.1: hydrogen bromide / water / 4 h / 110 °C / Inert atmosphere
6.1: triethylamine / dichloromethane / 3 h / 20 °C |
|
|
Multi-step reaction with 7 steps
1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 2 h / 20 °C
2: triethylamine / dichloromethane / 1 h / 20 °C
3: acetic acid; hydrogenchloride / water / 3 h / 20 °C
4: hydrogen; palladium 10% on activated carbon / methanol / 16 h
5: borane-THF / tetrahydrofuran / 16 h / 60 °C / Inert atmosphere
6: hydrogen bromide / water / 3 h / 100 °C
7: triethylamine / dichloromethane; tetrahydrofuran / 2 h / 20 °C |
|
|
Multi-step reaction with 6 steps
1.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 2 h / 20 °C / Large scale
1.2: 2 h / 20 °C / Large scale
2.1: hydrogenchloride; acetic acid / water / 16 h / 20 °C / Large scale
3.1: hydrogen; acetic acid; palladium on activated charcoal / 16 h / 20 °C
4.1: dimethylsulfide borane complex / tetrahydrofuran / 16 h / -5 °C / Inert atmosphere
4.2: 2 h / Reflux
5.1: hydrogen bromide / water / 4 h / 110 °C / Inert atmosphere
6.1: triethylamine / dichloromethane / 2 h / 20 °C |
|
Reference：
[1]Current Patent Assignee: CORTEVA INC; C.H. Boehringer Sohn AG & Co. KG; F.LLI GANCIA & C. SPA - US2014/73629, 2014, A1
[2]Taylor, Simon J.; Demont, Emmanuel H.; Gray, James; Deeks, Nigel; Patel, Aarti; Nguyen, Dung; Taylor, Maxine; Hood, Steve; Watson, Robert J.; Bit, Rino A.; McClure, Fiona; Ashall, Holly; Witherington, Jason
[Journal of Medicinal Chemistry, 2015, vol. 58, # 20, p. 8236 - 8256]
[3]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/24059, 2016, A1
- 32
-
[ 33797-36-3 ]
-
[ 1258856-18-6 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 7 steps
1.1: oxalyl dichloride / dichloromethane; N,N-dimethyl-formamide / 2 h / Inert atmosphere
1.2: 2 h / 20 °C
2.1: acetic acid; hydrogenchloride / 16 h / 20 °C
3.1: hydrogen; palladium on activated charcoal / acetic acid / 16 h / 20 °C / 2585.81 Torr
4.1: dimethylsulfide borane complex / tetrahydrofuran / 16 h / -5 °C / Inert atmosphere
5.1: hydrogen bromide / water / 4 h / 110 °C / Inert atmosphere
6.1: triethylamine / dichloromethane / 3 h / 20 °C
7.1: pyridine / 2 h / 20 °C / Inert atmosphere |
|
|
Multi-step reaction with 8 steps
1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 2 h / 20 °C
2: triethylamine / dichloromethane / 1 h / 20 °C
3: acetic acid; hydrogenchloride / water / 3 h / 20 °C
4: hydrogen; palladium 10% on activated carbon / methanol / 16 h
5: borane-THF / tetrahydrofuran / 16 h / 60 °C / Inert atmosphere
6: hydrogen bromide / water / 3 h / 100 °C
7: triethylamine / dichloromethane; tetrahydrofuran / 2 h / 20 °C
8: pyridine / dichloromethane / 1 h / -50 - 20 °C / Inert atmosphere |
|
|
Multi-step reaction with 7 steps
1.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 2 h / 20 °C / Large scale
1.2: 2 h / 20 °C / Large scale
2.1: hydrogenchloride; acetic acid / water / 16 h / 20 °C / Large scale
3.1: hydrogen; acetic acid; palladium on activated charcoal / 16 h / 20 °C
4.1: dimethylsulfide borane complex / tetrahydrofuran / 16 h / -5 °C / Inert atmosphere
4.2: 2 h / Reflux
5.1: hydrogen bromide / water / 4 h / 110 °C / Inert atmosphere
6.1: triethylamine / dichloromethane / 2 h / 20 °C
7.1: dichloromethane / 2 h / 20 °C / Inert atmosphere |
|
Reference：
[1]Current Patent Assignee: CORTEVA INC; C.H. Boehringer Sohn AG & Co. KG; F.LLI GANCIA & C. SPA - US2014/73629, 2014, A1
[2]Taylor, Simon J.; Demont, Emmanuel H.; Gray, James; Deeks, Nigel; Patel, Aarti; Nguyen, Dung; Taylor, Maxine; Hood, Steve; Watson, Robert J.; Bit, Rino A.; McClure, Fiona; Ashall, Holly; Witherington, Jason
[Journal of Medicinal Chemistry, 2015, vol. 58, # 20, p. 8236 - 8256]
[3]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/24059, 2016, A1
- 33
-
[ 33797-36-3 ]
-
[ 22483-09-6 ]
-
[ 871501-24-5 ]
| Yield | Reaction Conditions | Operation in experiment |
| 96% |
Stage #1: 2-(3-methoxy-2-methylphenyl)acetic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 2h; Large scale;
Stage #2: 2,2-dimethoxyethylamine With triethylamine In dichloromethane at 20℃; for 2h; Large scale; |
25 Example 25 Preparation of intermediate 7-Bromomethyl-6-methyl-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid tert-butyl ester (D-11)
To a stirred solution of (COCl)2 (8.18 mol) and DMF (70.000 ml) in DCM (7.5 L) is added D-11-1 (737 g, 4.09 mol). The mixture is stirred at room temperature for 2 h then concentrated under reduced pressure. The residue is added to a stirred solution of 2,2-dimethoxyethyl-1-amine (430 g, 4.09 mol) and TEA (454 g, 4.50 mol) in DCM (1000 ml). The mixture is stirred at room temperature for 2 h then concentrated under reduced pressure. The residue is purified by flash silica gel column chromatography to afford D-11-2 (1474 g, 96% yield). |
|
Stage #1: 2-(3-methoxy-2-methylphenyl)acetic acid With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide for 2h; Inert atmosphere;
Stage #2: 2,2-dimethoxyethylamine With triethylamine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 2h; |
19
Compound 19-5 (737.000 g, 4.090 mol) is added to a stirred solution of (COCl)2 (8.180 mol) and DMF (70.000 ml) in dichloromethane (7370.000 ml) under N2 atmosphere, followed by stirring for 2 h. TLC showed the reaction is completed. Then the mixture is evaporated. The residue was added to a stirred solution of 2,2-dimethoxyethyl-1-amine (429.996 g, 4.090 mol) and Et3N (454.388 g, 4.499 mol) in dichloromethane (1000 ml) at room temperature for 2 h. TLC showed the reaction is completed. The mixture is evaporated and the residue is purified by column to give compound 19-6. |
- 34
-
[ 55289-06-0 ]
-
[ 33797-36-3 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 4 steps
1.1: borane-THF / tetrahydrofuran / 3 h / 0 - 20 °C / Inert atmosphere
1.2: 20 °C / Inert atmosphere
2.1: methanesulfonyl chloride; triethylamine / dichloromethane / 2 h / 0 - 20 °C
3.1: N,N-dimethyl-formamide / 96 h / 90 °C
4.1: sodium hydroxide / ethanol; water / 48 h / Reflux
4.2: pH 2 |
|
|
Multi-step reaction with 4 steps
1: lithium aluminium tetrahydride / tetrahydrofuran / 1.5 h / 0 °C / Reflux
2: thionyl chloride / dichloromethane / 1 h / -10 °C / Reflux
3: N,N-dimethyl-formamide / 12 h / 20 °C
4: potassium hydroxide / ethanol / 5 h / Reflux; Large scale |
|
Reference：
[1]Taylor, Simon J.; Demont, Emmanuel H.; Gray, James; Deeks, Nigel; Patel, Aarti; Nguyen, Dung; Taylor, Maxine; Hood, Steve; Watson, Robert J.; Bit, Rino A.; McClure, Fiona; Ashall, Holly; Witherington, Jason
[Journal of Medicinal Chemistry, 2015, vol. 58, # 20, p. 8236 - 8256]
[2]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/24059, 2016, A1
- 35
-
[ 33797-36-3 ]
-
5-(3-(3-(1,3-dihydroxypropan-2-yl)-6-methyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile hydrochloride
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 14 steps
1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 2 h / 20 °C
2: triethylamine / dichloromethane / 1 h / 20 °C
3: acetic acid; hydrogenchloride / water / 3 h / 20 °C
4: hydrogen; palladium 10% on activated carbon / methanol / 16 h
5: borane-THF / tetrahydrofuran / 16 h / 60 °C / Inert atmosphere
6: hydrogen bromide / water / 3 h / 100 °C
7: triethylamine / dichloromethane; tetrahydrofuran / 2 h / 20 °C
8: pyridine / dichloromethane / 1 h / -50 - 20 °C / Inert atmosphere
9: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 6 h / 120 °C / Inert atmosphere
10: hydroxylamine hydrochloride; sodium hydrogencarbonate / ethanol / 48 h / Reflux
11: pyridine / toluene / 3 h / Reflux
12: dichloromethane / 2 h / 20 °C
13: sodium tris(acetoxy)borohydride / dichloromethane / 16 h / 20 °C
14: hydrogenchloride / tetrahydrofuran; water / 5 h / 20 °C |
|
Reference：
[1]Taylor, Simon J.; Demont, Emmanuel H.; Gray, James; Deeks, Nigel; Patel, Aarti; Nguyen, Dung; Taylor, Maxine; Hood, Steve; Watson, Robert J.; Bit, Rino A.; McClure, Fiona; Ashall, Holly; Witherington, Jason
[Journal of Medicinal Chemistry, 2015, vol. 58, # 20, p. 8236 - 8256]
- 36
-
[ 33797-36-3 ]
-
[ 1258856-17-5 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 9 steps
1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 2 h / 20 °C
2: triethylamine / dichloromethane / 1 h / 20 °C
3: acetic acid; hydrogenchloride / water / 3 h / 20 °C
4: hydrogen; palladium 10% on activated carbon / methanol / 16 h
5: borane-THF / tetrahydrofuran / 16 h / 60 °C / Inert atmosphere
6: hydrogen bromide / water / 3 h / 100 °C
7: triethylamine / dichloromethane; tetrahydrofuran / 2 h / 20 °C
8: pyridine / dichloromethane / 1 h / -50 - 20 °C / Inert atmosphere
9: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 6 h / 120 °C / Inert atmosphere |
|
Reference：
[1]Taylor, Simon J.; Demont, Emmanuel H.; Gray, James; Deeks, Nigel; Patel, Aarti; Nguyen, Dung; Taylor, Maxine; Hood, Steve; Watson, Robert J.; Bit, Rino A.; McClure, Fiona; Ashall, Holly; Witherington, Jason
[Journal of Medicinal Chemistry, 2015, vol. 58, # 20, p. 8236 - 8256]
- 37
-
[ 33797-36-3 ]
-
tert-butyl 7-(N'-hydroxycarbamimidoyl)-6-methyl-4,5-dihydro-1H-benzo[d]azepine-3(2H)-carboxylate
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 10 steps
1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 2 h / 20 °C
2: triethylamine / dichloromethane / 1 h / 20 °C
3: acetic acid; hydrogenchloride / water / 3 h / 20 °C
4: hydrogen; palladium 10% on activated carbon / methanol / 16 h
5: borane-THF / tetrahydrofuran / 16 h / 60 °C / Inert atmosphere
6: hydrogen bromide / water / 3 h / 100 °C
7: triethylamine / dichloromethane; tetrahydrofuran / 2 h / 20 °C
8: pyridine / dichloromethane / 1 h / -50 - 20 °C / Inert atmosphere
9: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 6 h / 120 °C / Inert atmosphere
10: hydroxylamine hydrochloride; sodium hydrogencarbonate / ethanol / 48 h / Reflux |
|
Reference：
[1]Taylor, Simon J.; Demont, Emmanuel H.; Gray, James; Deeks, Nigel; Patel, Aarti; Nguyen, Dung; Taylor, Maxine; Hood, Steve; Watson, Robert J.; Bit, Rino A.; McClure, Fiona; Ashall, Holly; Witherington, Jason
[Journal of Medicinal Chemistry, 2015, vol. 58, # 20, p. 8236 - 8256]
- 38
-
[ 33797-36-3 ]
-
[ 1258856-14-2 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 12 steps
1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 2 h / 20 °C
2: triethylamine / dichloromethane / 1 h / 20 °C
3: acetic acid; hydrogenchloride / water / 3 h / 20 °C
4: hydrogen; palladium 10% on activated carbon / methanol / 16 h
5: borane-THF / tetrahydrofuran / 16 h / 60 °C / Inert atmosphere
6: hydrogen bromide / water / 3 h / 100 °C
7: triethylamine / dichloromethane; tetrahydrofuran / 2 h / 20 °C
8: pyridine / dichloromethane / 1 h / -50 - 20 °C / Inert atmosphere
9: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 6 h / 120 °C / Inert atmosphere
10: hydroxylamine hydrochloride; sodium hydrogencarbonate / ethanol / 48 h / Reflux
11: pyridine / toluene / 3 h / Reflux
12: dichloromethane / 2 h / 20 °C |
|
Reference：
[1]Taylor, Simon J.; Demont, Emmanuel H.; Gray, James; Deeks, Nigel; Patel, Aarti; Nguyen, Dung; Taylor, Maxine; Hood, Steve; Watson, Robert J.; Bit, Rino A.; McClure, Fiona; Ashall, Holly; Witherington, Jason
[Journal of Medicinal Chemistry, 2015, vol. 58, # 20, p. 8236 - 8256]
- 39
-
[ 33797-36-3 ]
-
[ 1258856-15-3 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 11 steps
1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 2 h / 20 °C
2: triethylamine / dichloromethane / 1 h / 20 °C
3: acetic acid; hydrogenchloride / water / 3 h / 20 °C
4: hydrogen; palladium 10% on activated carbon / methanol / 16 h
5: borane-THF / tetrahydrofuran / 16 h / 60 °C / Inert atmosphere
6: hydrogen bromide / water / 3 h / 100 °C
7: triethylamine / dichloromethane; tetrahydrofuran / 2 h / 20 °C
8: pyridine / dichloromethane / 1 h / -50 - 20 °C / Inert atmosphere
9: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 6 h / 120 °C / Inert atmosphere
10: hydroxylamine hydrochloride; sodium hydrogencarbonate / ethanol / 48 h / Reflux
11: pyridine / toluene / 3 h / Reflux |
|
Reference：
[1]Taylor, Simon J.; Demont, Emmanuel H.; Gray, James; Deeks, Nigel; Patel, Aarti; Nguyen, Dung; Taylor, Maxine; Hood, Steve; Watson, Robert J.; Bit, Rino A.; McClure, Fiona; Ashall, Holly; Witherington, Jason
[Journal of Medicinal Chemistry, 2015, vol. 58, # 20, p. 8236 - 8256]
- 40
-
[ 33797-36-3 ]
-
C29H34N4O4
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 13 steps
1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 2 h / 20 °C
2: triethylamine / dichloromethane / 1 h / 20 °C
3: acetic acid; hydrogenchloride / water / 3 h / 20 °C
4: hydrogen; palladium 10% on activated carbon / methanol / 16 h
5: borane-THF / tetrahydrofuran / 16 h / 60 °C / Inert atmosphere
6: hydrogen bromide / water / 3 h / 100 °C
7: triethylamine / dichloromethane; tetrahydrofuran / 2 h / 20 °C
8: pyridine / dichloromethane / 1 h / -50 - 20 °C / Inert atmosphere
9: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 6 h / 120 °C / Inert atmosphere
10: hydroxylamine hydrochloride; sodium hydrogencarbonate / ethanol / 48 h / Reflux
11: pyridine / toluene / 3 h / Reflux
12: dichloromethane / 2 h / 20 °C
13: sodium tris(acetoxy)borohydride / dichloromethane / 16 h / 20 °C |
|
Reference：
[1]Taylor, Simon J.; Demont, Emmanuel H.; Gray, James; Deeks, Nigel; Patel, Aarti; Nguyen, Dung; Taylor, Maxine; Hood, Steve; Watson, Robert J.; Bit, Rino A.; McClure, Fiona; Ashall, Holly; Witherington, Jason
[Journal of Medicinal Chemistry, 2015, vol. 58, # 20, p. 8236 - 8256]
- 41
-
[ 33797-36-3 ]
-
[ 1258856-55-1 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 11 steps
1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 2 h / 20 °C
2: triethylamine / dichloromethane / 1 h / 20 °C
3: acetic acid; hydrogenchloride / water / 3 h / 20 °C
4: hydrogen; palladium 10% on activated carbon / methanol / 16 h
5: borane-THF / tetrahydrofuran / 16 h / 60 °C / Inert atmosphere
6: hydrogen bromide / water / 3 h / 100 °C
7: triethylamine / dichloromethane; tetrahydrofuran / 2 h / 20 °C
8: pyridine / dichloromethane / 1 h / -50 - 20 °C / Inert atmosphere
9: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 6 h / 120 °C / Inert atmosphere
10: hydroxylamine hydrochloride; sodium hydrogencarbonate / ethanol / 48 h / Reflux
11: N-ethylmorpholine;; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 4 h / 20 °C |
|
Reference：
[1]Taylor, Simon J.; Demont, Emmanuel H.; Gray, James; Deeks, Nigel; Patel, Aarti; Nguyen, Dung; Taylor, Maxine; Hood, Steve; Watson, Robert J.; Bit, Rino A.; McClure, Fiona; Ashall, Holly; Witherington, Jason
[Journal of Medicinal Chemistry, 2015, vol. 58, # 20, p. 8236 - 8256]
- 42
-
[ 33797-36-3 ]
-
[ 1258853-83-6 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 13 steps
1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 2 h / 20 °C
2: triethylamine / dichloromethane / 1 h / 20 °C
3: acetic acid; hydrogenchloride / water / 3 h / 20 °C
4: hydrogen; palladium 10% on activated carbon / methanol / 16 h
5: borane-THF / tetrahydrofuran / 16 h / 60 °C / Inert atmosphere
6: hydrogen bromide / water / 3 h / 100 °C
7: triethylamine / dichloromethane; tetrahydrofuran / 2 h / 20 °C
8: pyridine / dichloromethane / 1 h / -50 - 20 °C / Inert atmosphere
9: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 6 h / 120 °C / Inert atmosphere
10: hydroxylamine hydrochloride; sodium hydrogencarbonate / ethanol / 48 h / Reflux
11: pyridine / toluene / 3 h / Reflux
12: dichloromethane / 2 h / 20 °C
13: sodium tris(acetoxy)borohydride; acetic acid / dichloromethane / 92 h / 20 °C / Inert atmosphere |
|
Reference：
[1]Taylor, Simon J.; Demont, Emmanuel H.; Gray, James; Deeks, Nigel; Patel, Aarti; Nguyen, Dung; Taylor, Maxine; Hood, Steve; Watson, Robert J.; Bit, Rino A.; McClure, Fiona; Ashall, Holly; Witherington, Jason
[Journal of Medicinal Chemistry, 2015, vol. 58, # 20, p. 8236 - 8256]
- 43
-
[ 33797-36-3 ]
-
[ 871501-24-5 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 2 steps
1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 2 h / 20 °C
2: triethylamine / dichloromethane / 1 h / 20 °C |
|
Reference：
[1]Taylor, Simon J.; Demont, Emmanuel H.; Gray, James; Deeks, Nigel; Patel, Aarti; Nguyen, Dung; Taylor, Maxine; Hood, Steve; Watson, Robert J.; Bit, Rino A.; McClure, Fiona; Ashall, Holly; Witherington, Jason
[Journal of Medicinal Chemistry, 2015, vol. 58, # 20, p. 8236 - 8256]
- 44
-
[ 33797-36-3 ]
-
[ 1258853-82-5 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 13 steps
1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 2 h / 20 °C
2: triethylamine / dichloromethane / 1 h / 20 °C
3: acetic acid; hydrogenchloride / water / 3 h / 20 °C
4: hydrogen; palladium 10% on activated carbon / methanol / 16 h
5: borane-THF / tetrahydrofuran / 16 h / 60 °C / Inert atmosphere
6: hydrogen bromide / water / 3 h / 100 °C
7: triethylamine / dichloromethane; tetrahydrofuran / 2 h / 20 °C
8: pyridine / dichloromethane / 1 h / -50 - 20 °C / Inert atmosphere
9: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 6 h / 120 °C / Inert atmosphere
10: hydroxylamine hydrochloride; sodium hydrogencarbonate / ethanol / 48 h / Reflux
11: pyridine / toluene / 3 h / Reflux
12: dichloromethane / 2 h / 20 °C
13: sodium tris(acetoxy)borohydride; acetic acid / dichloromethane / 92 h / 20 °C / Inert atmosphere |
|
Reference：
[1]Taylor, Simon J.; Demont, Emmanuel H.; Gray, James; Deeks, Nigel; Patel, Aarti; Nguyen, Dung; Taylor, Maxine; Hood, Steve; Watson, Robert J.; Bit, Rino A.; McClure, Fiona; Ashall, Holly; Witherington, Jason
[Journal of Medicinal Chemistry, 2015, vol. 58, # 20, p. 8236 - 8256]
- 45
-
[ 33797-36-3 ]
-
7-bromomethyl-6-methyl-1,2,4,5-tetrahydrobenzo[d]azepine-3-carboxylic acid tert-butyl ester
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 10 steps
1.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 2 h / 20 °C / Large scale
1.2: 2 h / 20 °C / Large scale
2.1: hydrogenchloride; acetic acid / water / 16 h / 20 °C / Large scale
3.1: hydrogen; acetic acid; palladium on activated charcoal / 16 h / 20 °C
4.1: dimethylsulfide borane complex / tetrahydrofuran / 16 h / -5 °C / Inert atmosphere
4.2: 2 h / Reflux
5.1: hydrogen bromide / water / 4 h / 110 °C / Inert atmosphere
6.1: triethylamine / dichloromethane / 2 h / 20 °C
7.1: dichloromethane / 2 h / 20 °C / Inert atmosphere
8.1: palladium diacetate; 1,3-bis-(diphenylphosphino)propane; triethylamine / 12 h / 80 °C
9.1: lithium aluminium tetrahydride / trifluoroacetic acid / 2 h / -40 - 20 °C
10.1: N-ethyl-N,N-diisopropylamine; dibromotriphenylphosphorane / dichloromethane / 1 h / 0 °C |
|
- 46
-
[ 33797-36-3 ]
-
[ 1579517-90-0 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 8 steps
1.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 2 h / 20 °C / Large scale
1.2: 2 h / 20 °C / Large scale
2.1: hydrogenchloride; acetic acid / water / 16 h / 20 °C / Large scale
3.1: hydrogen; acetic acid; palladium on activated charcoal / 16 h / 20 °C
4.1: dimethylsulfide borane complex / tetrahydrofuran / 16 h / -5 °C / Inert atmosphere
4.2: 2 h / Reflux
5.1: hydrogen bromide / water / 4 h / 110 °C / Inert atmosphere
6.1: triethylamine / dichloromethane / 2 h / 20 °C
7.1: dichloromethane / 2 h / 20 °C / Inert atmosphere
8.1: palladium diacetate; 1,3-bis-(diphenylphosphino)propane; triethylamine / 12 h / 80 °C |
|
- 47
-
[ 33797-36-3 ]
-
[ 1579517-92-2 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 9 steps
1.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 2 h / 20 °C / Large scale
1.2: 2 h / 20 °C / Large scale
2.1: hydrogenchloride; acetic acid / water / 16 h / 20 °C / Large scale
3.1: hydrogen; acetic acid; palladium on activated charcoal / 16 h / 20 °C
4.1: dimethylsulfide borane complex / tetrahydrofuran / 16 h / -5 °C / Inert atmosphere
4.2: 2 h / Reflux
5.1: hydrogen bromide / water / 4 h / 110 °C / Inert atmosphere
6.1: triethylamine / dichloromethane / 2 h / 20 °C
7.1: dichloromethane / 2 h / 20 °C / Inert atmosphere
8.1: palladium diacetate; 1,3-bis-(diphenylphosphino)propane; triethylamine / 12 h / 80 °C
9.1: lithium aluminium tetrahydride / trifluoroacetic acid / 2 h / -40 - 20 °C |
|
- 48
-
[ 33797-36-3 ]
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5-methoxy-4-methyl-2,3-dihydrobenzofuran
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 2 steps
1.1: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / 0 - 23 °C / Inert atmosphere
2.1: triethylamine; p-tolyl-λ3-iodanediyl bis(2,2,2-trifluoroacetate) / 2,2,2-trifluoroethanol / 0.25 h / 0 °C / Inert atmosphere
2.2: 14 h / 23 °C / Inert atmosphere |
|
Reference：
[1]Alvarado, Joseph; Fournier, Jeremy; Zakarian, Armen
[Angewandte Chemie - International Edition, 2016, vol. 55, # 38, p. 11625 - 11628][Angew. Chem., 2016, vol. 128, p. 11797 - 11800]
Chemistry
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Material Science
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