Alternatived Products of [ 1627494-13-6 ]
Product Details of [ 1627494-13-6 ]
CAS No. : 1627494-13-6
MDL No. : MFCD27987908
Formula :
C24 H25 F2 N3 O4
Boiling Point :
-
Linear Structure Formula : -
InChI Key : LMJFJIDLEAWOQJ-CQSZACIVSA-N
M.W :
457.47
Pubchem ID : 52913813
Synonyms :
Chemical Name : (R)-8-(1-((3,5-Difluorophenyl)amino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide
Calculated chemistry of [ 1627494-13-6 ]
Physicochemical Properties
Num. heavy atoms :
33
Num. arom. heavy atoms :
16
Fraction Csp3 :
0.33
Num. rotatable bonds :
6
Num. H-bond acceptors :
6.0
Num. H-bond donors :
1.0
Molar Refractivity :
124.62
TPSA :
75.02 Ų
Pharmacokinetics
GI absorption :
High
BBB permeant :
Yes
P-gp substrate :
Yes
CYP1A2 inhibitor :
No
CYP2C19 inhibitor :
Yes
CYP2C9 inhibitor :
Yes
CYP2D6 inhibitor :
Yes
CYP3A4 inhibitor :
Yes
Log Kp (skin permeation) :
-6.93 cm/s
Lipophilicity
Log Po/w (iLOGP) :
3.85
Log Po/w (XLOGP3) :
3.04
Log Po/w (WLOGP) :
3.73
Log Po/w (MLOGP) :
2.45
Log Po/w (SILICOS-IT) :
4.14
Consensus Log Po/w :
3.44
Druglikeness
Lipinski :
0.0
Ghose :
None
Veber :
0.0
Egan :
0.0
Muegge :
0.0
Bioavailability Score :
0.55
Water Solubility
Log S (ESOL) :
-4.55
Solubility :
0.0128 mg/ml ; 0.0000279 mol/l
Class :
Moderately soluble
Log S (Ali) :
-4.28
Solubility :
0.0239 mg/ml ; 0.0000523 mol/l
Class :
Moderately soluble
Log S (SILICOS-IT) :
-7.29
Solubility :
0.0000236 mg/ml ; 0.0000000516 mol/l
Class :
Poorly soluble
Medicinal Chemistry
PAINS :
0.0 alert
Brenk :
0.0 alert
Leadlikeness :
1.0
Synthetic accessibility :
4.3
Safety of [ 1627494-13-6 ]
Application In Synthesis of [ 1627494-13-6 ]
* 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 [ 1627494-13-6 ]
1
[ 1296270-45-5 ]
[ 1627494-13-6 ]
Yield Reaction Conditions Operation in experiment
With diethylamine In methanol; acetonitrile Resolution of racemate;
Reference:
[1]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
2
[ CAS Unavailable ]
[ 1644433-41-9 ]
[ 1627494-13-6 ]
Yield Reaction Conditions Operation in experiment
With tris-(dibenzylideneacetone)dipalladium(0) ; caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 95℃; for 16h; Inert atmosphere; Sealed tube;
Reference:
[1]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
3
[ 1627494-13-6 ]
[ 77-78-1 ]
[ CAS Unavailable ]
Yield Reaction Conditions Operation in experiment
67.9%
Stage #1: 8-((1R)-1-(3,5-difluorophenylamino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide With lithium hexamethyldisilazane In tetrahydrofuran at -60 - -10℃; for 0.25h; Inert atmosphere;
Stage #2: dimethyl sulfate In tetrahydrofuran at -60 - 0℃; for 0.25h; Inert atmosphere;
Reference:
[1]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
4
[ 1296271-46-9 ]
[ 1627494-13-6 ]
Yield Reaction Conditions Operation in experiment
Multi-step reaction with 4 steps
1.1: O-(N-succinimidyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 1.5 h / 25 °C / Inert atmosphere
1.2: 0.5 h / Inert atmosphere
2.1: phosphorus tribromide / dichloromethane / 96 h / 25 °C / Inert atmosphere
3.1: N,N-dimethyl-formamide / 5 h / 50 °C / Inert atmosphere
4.1: diethylamine / acetonitrile; methanol / Resolution of racemate
Reference:
[1]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
5
[ CAS Unavailable ]
[ 1627494-13-6 ]
Yield Reaction Conditions Operation in experiment
Multi-step reaction with 8 steps
1.1: boron trifluoride diethyl etherate / toluene / 18 h / 25 °C / Inert atmosphere
1.2: 12 h / 90 °C / Inert atmosphere
2.1: sodium hydroxide; water / methanol / 16 h / 25 °C / Inert atmosphere
3.1: bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere
3.2: 0.42 h / 50 °C / Inert atmosphere
4.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 25 °C / Inert atmosphere
5.1: titanium(IV) isopropylate / tetrahydrofuran / 24 h / Inert atmosphere; Reflux
6.1: acetic acid; sodium cyanoborohydride / dichloromethane; methanol / 5 h / -15 °C / Inert atmosphere
7.1: hydrogenchloride / water; 1,4-dioxane / 1 h / 25 °C / Inert atmosphere
8.1: tris-(dibenzylideneacetone)dipalladium(0) ; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; caesium carbonate / 1,4-dioxane / 16 h / 95 °C / Inert atmosphere; Sealed tube
Multi-step reaction with 8 steps
1.1: boron trifluoride diethyl etherate / toluene / 18 h / 25 °C / Inert atmosphere
1.2: 12 h / 90 °C / Inert atmosphere
2.1: bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane / 21 h / 90 °C / Inert atmosphere
2.2: 0.5 h / 45 °C / Inert atmosphere
3.1: sodium tetrahydroborate / dichloromethane; methanol / 0.25 h / -10 °C / Inert atmosphere
4.1: sodium hydroxide; water / methanol / 1.25 h / -15 - 25 °C / Inert atmosphere
5.1: O-(N-succinimidyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 1.5 h / 25 °C / Inert atmosphere
5.2: 0.5 h / Inert atmosphere
6.1: phosphorus tribromide / dichloromethane / 96 h / 25 °C / Inert atmosphere
7.1: N,N-dimethyl-formamide / 5 h / 50 °C / Inert atmosphere
8.1: diethylamine / acetonitrile; methanol / Resolution of racemate
Multi-step reaction with 9 steps
1.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -65 - 0 °C / Inert atmosphere
1.2: 2 h / -65 - 25 °C / Inert atmosphere
2.1: trifluoromethylsulfonic anhydride / 1,2-dichloro-ethane / 18 h / 25 - 50 °C / Inert atmosphere
3.1: bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane / 21 h / 90 °C / Inert atmosphere
3.2: 0.5 h / 45 °C / Inert atmosphere
4.1: sodium tetrahydroborate / dichloromethane; methanol / 0.25 h / -10 °C / Inert atmosphere
5.1: sodium hydroxide; water / methanol / 1.25 h / -15 - 25 °C / Inert atmosphere
6.1: O-(N-succinimidyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 1.5 h / 25 °C / Inert atmosphere
6.2: 0.5 h / Inert atmosphere
7.1: phosphorus tribromide / dichloromethane / 96 h / 25 °C / Inert atmosphere
8.1: N,N-dimethyl-formamide / 5 h / 50 °C / Inert atmosphere
9.1: diethylamine / acetonitrile; methanol / Resolution of racemate
Multi-step reaction with 9 steps
1.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -65 - 0 °C / Inert atmosphere
1.2: 2 h / -65 - 25 °C / Inert atmosphere
2.1: trifluoromethylsulfonic anhydride / 1,2-dichloro-ethane / 18 h / 25 - 50 °C / Inert atmosphere
3.1: sodium hydroxide; water / methanol / 16 h / 25 °C / Inert atmosphere
4.1: bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere
4.2: 0.42 h / 50 °C / Inert atmosphere
5.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 25 °C / Inert atmosphere
6.1: titanium(IV) isopropylate / tetrahydrofuran / 24 h / Inert atmosphere; Reflux
7.1: acetic acid; sodium cyanoborohydride / dichloromethane; methanol / 5 h / -15 °C / Inert atmosphere
8.1: hydrogenchloride / water; 1,4-dioxane / 1 h / 25 °C / Inert atmosphere
9.1: tris-(dibenzylideneacetone)dipalladium(0) ; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; caesium carbonate / 1,4-dioxane / 16 h / 95 °C / Inert atmosphere; Sealed tube
Reference:
[1]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
[2]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
[3]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
[4]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
6
[ 1296271-49-2 ]
[ 1627494-13-6 ]
Yield Reaction Conditions Operation in experiment
Multi-step reaction with 3 steps
1: phosphorus tribromide / dichloromethane / 96 h / 25 °C / Inert atmosphere
2: N,N-dimethyl-formamide / 5 h / 50 °C / Inert atmosphere
3: diethylamine / acetonitrile; methanol / Resolution of racemate
Reference:
[1]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
7
[ CAS Unavailable ]
[ 1627494-13-6 ]
Yield Reaction Conditions Operation in experiment
Multi-step reaction with 2 steps
1: N,N-dimethyl-formamide / 5 h / 50 °C / Inert atmosphere
2: diethylamine / acetonitrile; methanol / Resolution of racemate
Reference:
[1]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
8
[ 1296271-35-6 ]
[ 1627494-13-6 ]
Yield Reaction Conditions Operation in experiment
Multi-step reaction with 6 steps
1.1: bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere
1.2: 0.42 h / 50 °C / Inert atmosphere
2.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 25 °C / Inert atmosphere
3.1: titanium(IV) isopropylate / tetrahydrofuran / 24 h / Inert atmosphere; Reflux
4.1: acetic acid; sodium cyanoborohydride / dichloromethane; methanol / 5 h / -15 °C / Inert atmosphere
5.1: hydrogenchloride / water; 1,4-dioxane / 1 h / 25 °C / Inert atmosphere
6.1: tris-(dibenzylideneacetone)dipalladium(0) ; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; caesium carbonate / 1,4-dioxane / 16 h / 95 °C / Inert atmosphere; Sealed tube
Reference:
[1]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
9
[ 1296271-36-7 ]
[ 1627494-13-6 ]
Yield Reaction Conditions Operation in experiment
Multi-step reaction with 5 steps
1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 25 °C / Inert atmosphere
2: titanium(IV) isopropylate / tetrahydrofuran / 24 h / Inert atmosphere; Reflux
3: acetic acid; sodium cyanoborohydride / dichloromethane; methanol / 5 h / -15 °C / Inert atmosphere
4: hydrogenchloride / water; 1,4-dioxane / 1 h / 25 °C / Inert atmosphere
5: tris-(dibenzylideneacetone)dipalladium(0) ; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; caesium carbonate / 1,4-dioxane / 16 h / 95 °C / Inert atmosphere; Sealed tube
Reference:
[1]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
10
[ 1296271-61-8 ]
[ 1627494-13-6 ]
Yield Reaction Conditions Operation in experiment
Multi-step reaction with 4 steps
1: titanium(IV) isopropylate / tetrahydrofuran / 24 h / Inert atmosphere; Reflux
2: acetic acid; sodium cyanoborohydride / dichloromethane; methanol / 5 h / -15 °C / Inert atmosphere
3: hydrogenchloride / water; 1,4-dioxane / 1 h / 25 °C / Inert atmosphere
4: tris-(dibenzylideneacetone)dipalladium(0) ; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; caesium carbonate / 1,4-dioxane / 16 h / 95 °C / Inert atmosphere; Sealed tube
Multi-step reaction with 3 steps
1.1: triethylammonium formate; C4 -[(S,S)-teth-MsDPEN RuCl] / tetrahydrofuran; methanol / 3 h / 55 °C / Inert atmosphere; Large scale
2.1: triphenylphosphine / acetonitrile / 0.5 h / 20 °C / Inert atmosphere; Large scale
2.2: 25 h / 3 - 20 °C / Inert atmosphere; Large scale
3.1: mercaptoacetic acid; potassium carbonate / water; dimethyl sulfoxide / 3 h / 30 - 60 °C / Inert atmosphere; Large scale
Reference:
[1]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
[2]Moore, Peter R.; Muir, James C.; Dubiez, Jerome; Leslie, Kevin W.; Tomlin, Paula; McCormick, Marc; Janbon, Sophie L.; Cornwall, Philip; Ryberg, Per; Berg, Robert
[Organic Process Research and Development, 2021, vol. 25, # 8, p. 1889 - 1897]
11
[ 1296271-62-9 ]
[ 1627494-13-6 ]
Yield Reaction Conditions Operation in experiment
Multi-step reaction with 3 steps
1: acetic acid; sodium cyanoborohydride / dichloromethane; methanol / 5 h / -15 °C / Inert atmosphere
2: hydrogenchloride / water; 1,4-dioxane / 1 h / 25 °C / Inert atmosphere
3: tris-(dibenzylideneacetone)dipalladium(0) ; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; caesium carbonate / 1,4-dioxane / 16 h / 95 °C / Inert atmosphere; Sealed tube
Reference:
[1]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
12
[ 1296271-33-4 ]
[ 1627494-13-6 ]
Yield Reaction Conditions Operation in experiment
Multi-step reaction with 7 steps
1.1: sodium hydroxide; water / methanol / 16 h / 25 °C / Inert atmosphere
2.1: bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere
2.2: 0.42 h / 50 °C / Inert atmosphere
3.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 25 °C / Inert atmosphere
4.1: titanium(IV) isopropylate / tetrahydrofuran / 24 h / Inert atmosphere; Reflux
5.1: acetic acid; sodium cyanoborohydride / dichloromethane; methanol / 5 h / -15 °C / Inert atmosphere
6.1: hydrogenchloride / water; 1,4-dioxane / 1 h / 25 °C / Inert atmosphere
7.1: tris-(dibenzylideneacetone)dipalladium(0) ; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; caesium carbonate / 1,4-dioxane / 16 h / 95 °C / Inert atmosphere; Sealed tube
Multi-step reaction with 7 steps
1.1: bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane / 21 h / 90 °C / Inert atmosphere
1.2: 0.5 h / 45 °C / Inert atmosphere
2.1: sodium tetrahydroborate / dichloromethane; methanol / 0.25 h / -10 °C / Inert atmosphere
3.1: sodium hydroxide; water / methanol / 1.25 h / -15 - 25 °C / Inert atmosphere
4.1: O-(N-succinimidyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 1.5 h / 25 °C / Inert atmosphere
4.2: 0.5 h / Inert atmosphere
5.1: phosphorus tribromide / dichloromethane / 96 h / 25 °C / Inert atmosphere
6.1: N,N-dimethyl-formamide / 5 h / 50 °C / Inert atmosphere
7.1: diethylamine / acetonitrile; methanol / Resolution of racemate
Reference:
[1]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
[2]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
13
[ 1644410-91-2 ]
[ 1627494-13-6 ]
Yield Reaction Conditions Operation in experiment
Multi-step reaction with 2 steps
1: hydrogenchloride / water; 1,4-dioxane / 1 h / 25 °C / Inert atmosphere
2: tris-(dibenzylideneacetone)dipalladium(0) ; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; caesium carbonate / 1,4-dioxane / 16 h / 95 °C / Inert atmosphere; Sealed tube
Reference:
[1]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
14
[ 29415-97-2 ]
8-((1R)-1-(3,5-difluorophenylamino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide
[ No CAS ]
Reference:
[1]Journal of Medicinal Chemistry,2015,vol. 58,p. 943 - 962
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 943 - 962
[3]Journal of Medicinal Chemistry,2015,vol. 58,p. 943 - 962
[4]Journal of Medicinal Chemistry,2015,vol. 58,p. 943 - 962
15
[ CAS Unavailable ]
[ 1627494-13-6 ]
Yield Reaction Conditions Operation in experiment
Multi-step reaction with 10 steps
1.1: bromine; pyridine / dichloromethane / 2 h / 0 - 25 °C / Inert atmosphere
2.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -65 - 0 °C / Inert atmosphere
2.2: 2 h / -65 - 25 °C / Inert atmosphere
3.1: trifluoromethylsulfonic anhydride / 1,2-dichloro-ethane / 18 h / 25 - 50 °C / Inert atmosphere
4.1: sodium hydroxide; water / methanol / 16 h / 25 °C / Inert atmosphere
5.1: bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere
5.2: 0.42 h / 50 °C / Inert atmosphere
6.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 25 °C / Inert atmosphere
7.1: titanium(IV) isopropylate / tetrahydrofuran / 24 h / Inert atmosphere; Reflux
8.1: acetic acid; sodium cyanoborohydride / dichloromethane; methanol / 5 h / -15 °C / Inert atmosphere
9.1: hydrogenchloride / water; 1,4-dioxane / 1 h / 25 °C / Inert atmosphere
10.1: tris-(dibenzylideneacetone)dipalladium(0) ; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; caesium carbonate / 1,4-dioxane / 16 h / 95 °C / Inert atmosphere; Sealed tube
Multi-step reaction with 10 steps
1.1: bromine; pyridine / dichloromethane / 2 h / 0 - 25 °C / Inert atmosphere
2.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -65 - 0 °C / Inert atmosphere
2.2: 2 h / -65 - 25 °C / Inert atmosphere
3.1: trifluoromethylsulfonic anhydride / 1,2-dichloro-ethane / 18 h / 25 - 50 °C / Inert atmosphere
4.1: bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane / 21 h / 90 °C / Inert atmosphere
4.2: 0.5 h / 45 °C / Inert atmosphere
5.1: sodium tetrahydroborate / dichloromethane; methanol / 0.25 h / -10 °C / Inert atmosphere
6.1: sodium hydroxide; water / methanol / 1.25 h / -15 - 25 °C / Inert atmosphere
7.1: O-(N-succinimidyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 1.5 h / 25 °C / Inert atmosphere
7.2: 0.5 h / Inert atmosphere
8.1: phosphorus tribromide / dichloromethane / 96 h / 25 °C / Inert atmosphere
9.1: N,N-dimethyl-formamide / 5 h / 50 °C / Inert atmosphere
10.1: diethylamine / acetonitrile; methanol / Resolution of racemate
Multi-step reaction with 9 steps
1.1: bromine; pyridine / dichloromethane / 2 h / 0 - 25 °C / Inert atmosphere
2.1: boron trifluoride diethyl etherate / toluene / 18 h / 25 °C / Inert atmosphere
2.2: 12 h / 90 °C / Inert atmosphere
3.1: sodium hydroxide; water / methanol / 16 h / 25 °C / Inert atmosphere
4.1: bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere
4.2: 0.42 h / 50 °C / Inert atmosphere
5.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 25 °C / Inert atmosphere
6.1: titanium(IV) isopropylate / tetrahydrofuran / 24 h / Inert atmosphere; Reflux
7.1: acetic acid; sodium cyanoborohydride / dichloromethane; methanol / 5 h / -15 °C / Inert atmosphere
8.1: hydrogenchloride / water; 1,4-dioxane / 1 h / 25 °C / Inert atmosphere
9.1: tris-(dibenzylideneacetone)dipalladium(0) ; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; caesium carbonate / 1,4-dioxane / 16 h / 95 °C / Inert atmosphere; Sealed tube
Multi-step reaction with 9 steps
1.1: bromine; pyridine / dichloromethane / 2 h / 0 - 25 °C / Inert atmosphere
2.1: boron trifluoride diethyl etherate / toluene / 18 h / 25 °C / Inert atmosphere
2.2: 12 h / 90 °C / Inert atmosphere
3.1: bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane / 21 h / 90 °C / Inert atmosphere
3.2: 0.5 h / 45 °C / Inert atmosphere
4.1: sodium tetrahydroborate / dichloromethane; methanol / 0.25 h / -10 °C / Inert atmosphere
5.1: sodium hydroxide; water / methanol / 1.25 h / -15 - 25 °C / Inert atmosphere
6.1: O-(N-succinimidyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 1.5 h / 25 °C / Inert atmosphere
6.2: 0.5 h / Inert atmosphere
7.1: phosphorus tribromide / dichloromethane / 96 h / 25 °C / Inert atmosphere
8.1: N,N-dimethyl-formamide / 5 h / 50 °C / Inert atmosphere
9.1: diethylamine / acetonitrile; methanol / Resolution of racemate
Reference:
[1]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
[2]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
[3]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
[4]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
16
[ CAS Unavailable ]
[ 1627494-13-6 ]
Yield Reaction Conditions Operation in experiment
Multi-step reaction with 11 steps
1.1: bromine / dichloromethane / 24 h / 0 - 25 °C / Inert atmosphere
2.1: triethylamine; 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate / ethanol / 70 °C / Inert atmosphere
2.2: 2 h / 25 °C
3.1: bromine; pyridine / dichloromethane / 2 h / 0 - 25 °C / Inert atmosphere
4.1: boron trifluoride diethyl etherate / toluene / 18 h / 25 °C / Inert atmosphere
4.2: 12 h / 90 °C / Inert atmosphere
5.1: sodium hydroxide; water / methanol / 16 h / 25 °C / Inert atmosphere
6.1: bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere
6.2: 0.42 h / 50 °C / Inert atmosphere
7.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 25 °C / Inert atmosphere
8.1: titanium(IV) isopropylate / tetrahydrofuran / 24 h / Inert atmosphere; Reflux
9.1: acetic acid; sodium cyanoborohydride / dichloromethane; methanol / 5 h / -15 °C / Inert atmosphere
10.1: hydrogenchloride / water; 1,4-dioxane / 1 h / 25 °C / Inert atmosphere
11.1: tris-(dibenzylideneacetone)dipalladium(0) ; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; caesium carbonate / 1,4-dioxane / 16 h / 95 °C / Inert atmosphere; Sealed tube
Multi-step reaction with 11 steps
1.1: bromine / dichloromethane / 24 h / 0 - 25 °C / Inert atmosphere
2.1: triethylamine; 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate / ethanol / 70 °C / Inert atmosphere
2.2: 2 h / 25 °C
3.1: bromine; pyridine / dichloromethane / 2 h / 0 - 25 °C / Inert atmosphere
4.1: boron trifluoride diethyl etherate / toluene / 18 h / 25 °C / Inert atmosphere
4.2: 12 h / 90 °C / Inert atmosphere
5.1: bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane / 21 h / 90 °C / Inert atmosphere
5.2: 0.5 h / 45 °C / Inert atmosphere
6.1: sodium tetrahydroborate / dichloromethane; methanol / 0.25 h / -10 °C / Inert atmosphere
7.1: sodium hydroxide; water / methanol / 1.25 h / -15 - 25 °C / Inert atmosphere
8.1: O-(N-succinimidyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 1.5 h / 25 °C / Inert atmosphere
8.2: 0.5 h / Inert atmosphere
9.1: phosphorus tribromide / dichloromethane / 96 h / 25 °C / Inert atmosphere
10.1: N,N-dimethyl-formamide / 5 h / 50 °C / Inert atmosphere
11.1: diethylamine / acetonitrile; methanol / Resolution of racemate
Multi-step reaction with 12 steps
1.1: bromine / dichloromethane / 24 h / 0 - 25 °C / Inert atmosphere
2.1: triethylamine; 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate / ethanol / 70 °C / Inert atmosphere
2.2: 2 h / 25 °C
3.1: bromine; pyridine / dichloromethane / 2 h / 0 - 25 °C / Inert atmosphere
4.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -65 - 0 °C / Inert atmosphere
4.2: 2 h / -65 - 25 °C / Inert atmosphere
5.1: trifluoromethylsulfonic anhydride / 1,2-dichloro-ethane / 18 h / 25 - 50 °C / Inert atmosphere
6.1: sodium hydroxide; water / methanol / 16 h / 25 °C / Inert atmosphere
7.1: bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere
7.2: 0.42 h / 50 °C / Inert atmosphere
8.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 25 °C / Inert atmosphere
9.1: titanium(IV) isopropylate / tetrahydrofuran / 24 h / Inert atmosphere; Reflux
10.1: acetic acid; sodium cyanoborohydride / dichloromethane; methanol / 5 h / -15 °C / Inert atmosphere
11.1: hydrogenchloride / water; 1,4-dioxane / 1 h / 25 °C / Inert atmosphere
12.1: tris-(dibenzylideneacetone)dipalladium(0) ; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; caesium carbonate / 1,4-dioxane / 16 h / 95 °C / Inert atmosphere; Sealed tube
Multi-step reaction with 12 steps
1.1: bromine / dichloromethane / 24 h / 0 - 25 °C / Inert atmosphere
2.1: triethylamine; 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate / ethanol / 70 °C / Inert atmosphere
2.2: 2 h / 25 °C
3.1: bromine; pyridine / dichloromethane / 2 h / 0 - 25 °C / Inert atmosphere
4.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -65 - 0 °C / Inert atmosphere
4.2: 2 h / -65 - 25 °C / Inert atmosphere
5.1: trifluoromethylsulfonic anhydride / 1,2-dichloro-ethane / 18 h / 25 - 50 °C / Inert atmosphere
6.1: bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane / 21 h / 90 °C / Inert atmosphere
6.2: 0.5 h / 45 °C / Inert atmosphere
7.1: sodium tetrahydroborate / dichloromethane; methanol / 0.25 h / -10 °C / Inert atmosphere
8.1: sodium hydroxide; water / methanol / 1.25 h / -15 - 25 °C / Inert atmosphere
9.1: O-(N-succinimidyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 1.5 h / 25 °C / Inert atmosphere
9.2: 0.5 h / Inert atmosphere
10.1: phosphorus tribromide / dichloromethane / 96 h / 25 °C / Inert atmosphere
11.1: N,N-dimethyl-formamide / 5 h / 50 °C / Inert atmosphere
12.1: diethylamine / acetonitrile; methanol / Resolution of racemate
Reference:
[1]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
[2]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
[3]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
[4]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
17
[ CAS Unavailable ]
[ 1627494-13-6 ]
Yield Reaction Conditions Operation in experiment
Multi-step reaction with 10 steps
1.1: thionyl chloride / 3 h / 80 °C / Inert atmosphere
2.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -65 - 0 °C / Inert atmosphere
2.2: 2 h / -65 - 25 °C / Inert atmosphere
3.1: trifluoromethylsulfonic anhydride / 1,2-dichloro-ethane / 18 h / 25 - 50 °C / Inert atmosphere
4.1: sodium hydroxide; water / methanol / 16 h / 25 °C / Inert atmosphere
5.1: bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere
5.2: 0.42 h / 50 °C / Inert atmosphere
6.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 25 °C / Inert atmosphere
7.1: titanium(IV) isopropylate / tetrahydrofuran / 24 h / Inert atmosphere; Reflux
8.1: acetic acid; sodium cyanoborohydride / dichloromethane; methanol / 5 h / -15 °C / Inert atmosphere
9.1: hydrogenchloride / water; 1,4-dioxane / 1 h / 25 °C / Inert atmosphere
10.1: tris-(dibenzylideneacetone)dipalladium(0) ; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; caesium carbonate / 1,4-dioxane / 16 h / 95 °C / Inert atmosphere; Sealed tube
Multi-step reaction with 10 steps
1.1: thionyl chloride / 3 h / 80 °C / Inert atmosphere
2.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -65 - 0 °C / Inert atmosphere
2.2: 2 h / -65 - 25 °C / Inert atmosphere
3.1: trifluoromethylsulfonic anhydride / 1,2-dichloro-ethane / 18 h / 25 - 50 °C / Inert atmosphere
4.1: bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane / 21 h / 90 °C / Inert atmosphere
4.2: 0.5 h / 45 °C / Inert atmosphere
5.1: sodium tetrahydroborate / dichloromethane; methanol / 0.25 h / -10 °C / Inert atmosphere
6.1: sodium hydroxide; water / methanol / 1.25 h / -15 - 25 °C / Inert atmosphere
7.1: O-(N-succinimidyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 1.5 h / 25 °C / Inert atmosphere
7.2: 0.5 h / Inert atmosphere
8.1: phosphorus tribromide / dichloromethane / 96 h / 25 °C / Inert atmosphere
9.1: N,N-dimethyl-formamide / 5 h / 50 °C / Inert atmosphere
10.1: diethylamine / acetonitrile; methanol / Resolution of racemate
Multi-step reaction with 9 steps
1.1: thionyl chloride / 3 h / 80 °C / Inert atmosphere
2.1: boron trifluoride diethyl etherate / toluene / 18 h / 25 °C / Inert atmosphere
2.2: 12 h / 90 °C / Inert atmosphere
3.1: sodium hydroxide; water / methanol / 16 h / 25 °C / Inert atmosphere
4.1: bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere
4.2: 0.42 h / 50 °C / Inert atmosphere
5.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 25 °C / Inert atmosphere
6.1: titanium(IV) isopropylate / tetrahydrofuran / 24 h / Inert atmosphere; Reflux
7.1: acetic acid; sodium cyanoborohydride / dichloromethane; methanol / 5 h / -15 °C / Inert atmosphere
8.1: hydrogenchloride / water; 1,4-dioxane / 1 h / 25 °C / Inert atmosphere
9.1: tris-(dibenzylideneacetone)dipalladium(0) ; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; caesium carbonate / 1,4-dioxane / 16 h / 95 °C / Inert atmosphere; Sealed tube
Multi-step reaction with 9 steps
1.1: thionyl chloride / 3 h / 80 °C / Inert atmosphere
2.1: boron trifluoride diethyl etherate / toluene / 18 h / 25 °C / Inert atmosphere
2.2: 12 h / 90 °C / Inert atmosphere
3.1: bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane / 21 h / 90 °C / Inert atmosphere
3.2: 0.5 h / 45 °C / Inert atmosphere
4.1: sodium tetrahydroborate / dichloromethane; methanol / 0.25 h / -10 °C / Inert atmosphere
5.1: sodium hydroxide; water / methanol / 1.25 h / -15 - 25 °C / Inert atmosphere
6.1: O-(N-succinimidyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 1.5 h / 25 °C / Inert atmosphere
6.2: 0.5 h / Inert atmosphere
7.1: phosphorus tribromide / dichloromethane / 96 h / 25 °C / Inert atmosphere
8.1: N,N-dimethyl-formamide / 5 h / 50 °C / Inert atmosphere
9.1: diethylamine / acetonitrile; methanol / Resolution of racemate
Reference:
[1]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
[2]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
[3]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
[4]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
18
[ CAS Unavailable ]
[ 1627494-13-6 ]
Yield Reaction Conditions Operation in experiment
Multi-step reaction with 8 steps
1.1: trifluoromethylsulfonic anhydride / 1,2-dichloro-ethane / 18 h / 25 - 50 °C / Inert atmosphere
2.1: sodium hydroxide; water / methanol / 16 h / 25 °C / Inert atmosphere
3.1: bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere
3.2: 0.42 h / 50 °C / Inert atmosphere
4.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 25 °C / Inert atmosphere
5.1: titanium(IV) isopropylate / tetrahydrofuran / 24 h / Inert atmosphere; Reflux
6.1: acetic acid; sodium cyanoborohydride / dichloromethane; methanol / 5 h / -15 °C / Inert atmosphere
7.1: hydrogenchloride / water; 1,4-dioxane / 1 h / 25 °C / Inert atmosphere
8.1: tris-(dibenzylideneacetone)dipalladium(0) ; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; caesium carbonate / 1,4-dioxane / 16 h / 95 °C / Inert atmosphere; Sealed tube
Multi-step reaction with 8 steps
1.1: trifluoromethylsulfonic anhydride / 1,2-dichloro-ethane / 18 h / 25 - 50 °C / Inert atmosphere
2.1: bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane / 21 h / 90 °C / Inert atmosphere
2.2: 0.5 h / 45 °C / Inert atmosphere
3.1: sodium tetrahydroborate / dichloromethane; methanol / 0.25 h / -10 °C / Inert atmosphere
4.1: sodium hydroxide; water / methanol / 1.25 h / -15 - 25 °C / Inert atmosphere
5.1: O-(N-succinimidyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 1.5 h / 25 °C / Inert atmosphere
5.2: 0.5 h / Inert atmosphere
6.1: phosphorus tribromide / dichloromethane / 96 h / 25 °C / Inert atmosphere
7.1: N,N-dimethyl-formamide / 5 h / 50 °C / Inert atmosphere
8.1: diethylamine / acetonitrile; methanol / Resolution of racemate
Reference:
[1]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
[2]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
19
[ 1296271-39-0 ]
[ 1627494-13-6 ]
Yield Reaction Conditions Operation in experiment
Multi-step reaction with 6 steps
1.1: sodium tetrahydroborate / dichloromethane; methanol / 0.25 h / -10 °C / Inert atmosphere
2.1: sodium hydroxide; water / methanol / 1.25 h / -15 - 25 °C / Inert atmosphere
3.1: O-(N-succinimidyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 1.5 h / 25 °C / Inert atmosphere
3.2: 0.5 h / Inert atmosphere
4.1: phosphorus tribromide / dichloromethane / 96 h / 25 °C / Inert atmosphere
5.1: N,N-dimethyl-formamide / 5 h / 50 °C / Inert atmosphere
6.1: diethylamine / acetonitrile; methanol / Resolution of racemate
Reference:
[1]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
20
[ 1296271-40-3 ]
[ 1627494-13-6 ]
Yield Reaction Conditions Operation in experiment
Multi-step reaction with 5 steps
1.1: sodium hydroxide; water / methanol / 1.25 h / -15 - 25 °C / Inert atmosphere
2.1: O-(N-succinimidyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 1.5 h / 25 °C / Inert atmosphere
2.2: 0.5 h / Inert atmosphere
3.1: phosphorus tribromide / dichloromethane / 96 h / 25 °C / Inert atmosphere
4.1: N,N-dimethyl-formamide / 5 h / 50 °C / Inert atmosphere
5.1: diethylamine / acetonitrile; methanol / Resolution of racemate
Reference:
[1]Barlaam, Bernard; Cosulich, Sabina; Degorce, Sébastien; Fitzek, Martina; Green, Stephen; Hancox, Urs; Lambert-Van Der Brempt, Christine; Lohmann, Jean-Jacques; Maudet, Mickaël; Morgentin, Rémy; Pasquet, Marie-Jeanne; Péru, Aurélien; Plé, Patrick; Saleh, Twana; Vautier, Michel; Walker, Mike; Ward, Lara; Warin, Nicolas
[Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962]
21
[ CAS Unavailable ]
[ 1627494-13-6 ]
Yield Reaction Conditions Operation in experiment
100 % ee
With potassium carbonate; mercaptoacetic acid In water; dimethyl sulfoxide at 30 - 60℃; for 3h; Inert atmosphere; Large scale; enantioselective reaction;
Reference:
[1]Moore, Peter R.; Muir, James C.; Dubiez, Jerome; Leslie, Kevin W.; Tomlin, Paula; McCormick, Marc; Janbon, Sophie L.; Cornwall, Philip; Ryberg, Per; Berg, Robert
[Organic Process Research and Development, 2021, vol. 25, # 8, p. 1889 - 1897]
22
[ 881766-59-2 ]
[ 2663665-47-0 ]
[ 1627494-13-6 ]
Yield Reaction Conditions Operation in experiment
Multi-step reaction with 2 steps
1.1: triphenylphosphine / acetonitrile / 0.5 h / 20 °C / Inert atmosphere; Large scale
1.2: 25 h / 3 - 20 °C / Inert atmosphere; Large scale
2.1: mercaptoacetic acid; potassium carbonate / water; dimethyl sulfoxide / 3 h / 30 - 60 °C / Inert atmosphere; Large scale
Reference:
[1]Moore, Peter R.; Muir, James C.; Dubiez, Jerome; Leslie, Kevin W.; Tomlin, Paula; McCormick, Marc; Janbon, Sophie L.; Cornwall, Philip; Ryberg, Per; Berg, Robert
[Organic Process Research and Development, 2021, vol. 25, # 8, p. 1889 - 1897]
23
[ 372-39-4 ]
[ 1627494-13-6 ]
Yield Reaction Conditions Operation in experiment
Multi-step reaction with 3 steps
1.1: pyridine; dmap / Inert atmosphere
2.1: triphenylphosphine / acetonitrile / 0.5 h / 20 °C / Inert atmosphere; Large scale
2.2: 25 h / 3 - 20 °C / Inert atmosphere; Large scale
3.1: mercaptoacetic acid; potassium carbonate / water; dimethyl sulfoxide / 3 h / 30 - 60 °C / Inert atmosphere; Large scale
Reference:
[1]Moore, Peter R.; Muir, James C.; Dubiez, Jerome; Leslie, Kevin W.; Tomlin, Paula; McCormick, Marc; Janbon, Sophie L.; Cornwall, Philip; Ryberg, Per; Berg, Robert
[Organic Process Research and Development, 2021, vol. 25, # 8, p. 1889 - 1897]
24
[ CAS Unavailable ]
[ 1627494-13-6 ]
Yield Reaction Conditions Operation in experiment
Multi-step reaction with 5 steps
1.1: potassium carbonate; 1,3-bis-(diphenylphosphino)propane; palladium diacetate / water / 80 °C / Inert atmosphere; Large scale
2.1: phosphoric acid / water / 35 °C / Inert atmosphere; Large scale
3.1: triethylammonium formate; C4 -[(S,S)-teth-MsDPEN RuCl] / tetrahydrofuran; methanol / 3 h / 55 °C / Inert atmosphere; Large scale
4.1: triphenylphosphine / acetonitrile / 0.5 h / 20 °C / Inert atmosphere; Large scale
4.2: 25 h / 3 - 20 °C / Inert atmosphere; Large scale
5.1: mercaptoacetic acid; potassium carbonate / water; dimethyl sulfoxide / 3 h / 30 - 60 °C / Inert atmosphere; Large scale
Reference:
[1]Moore, Peter R.; Muir, James C.; Dubiez, Jerome; Leslie, Kevin W.; Tomlin, Paula; McCormick, Marc; Janbon, Sophie L.; Cornwall, Philip; Ryberg, Per; Berg, Robert
[Organic Process Research and Development, 2021, vol. 25, # 8, p. 1889 - 1897]
25
[ CAS Unavailable ]
[ 1627494-13-6 ]
Yield Reaction Conditions Operation in experiment
Multi-step reaction with 4 steps
1.1: phosphoric acid / water / 35 °C / Inert atmosphere; Large scale
2.1: triethylammonium formate; C4 -[(S,S)-teth-MsDPEN RuCl] / tetrahydrofuran; methanol / 3 h / 55 °C / Inert atmosphere; Large scale
3.1: triphenylphosphine / acetonitrile / 0.5 h / 20 °C / Inert atmosphere; Large scale
3.2: 25 h / 3 - 20 °C / Inert atmosphere; Large scale
4.1: mercaptoacetic acid; potassium carbonate / water; dimethyl sulfoxide / 3 h / 30 - 60 °C / Inert atmosphere; Large scale
Reference:
[1]Moore, Peter R.; Muir, James C.; Dubiez, Jerome; Leslie, Kevin W.; Tomlin, Paula; McCormick, Marc; Janbon, Sophie L.; Cornwall, Philip; Ryberg, Per; Berg, Robert
[Organic Process Research and Development, 2021, vol. 25, # 8, p. 1889 - 1897]