(S)-Bicalutamide-d4
Número de catálogo B1140949
Peso molecular: 434.4
Clave InChI:
Atención: Solo para uso de investigación. No para uso humano o veterinario.
Patent
US07186854B2
Procedure details
180 mg of the chiral epoxide of example 17 was dissolved in a mixture of 12 ml chloroform and 12 ml of water. 133 mg of sodium-p-fluorobenzenesulfinate and 107 mg of tetrabutylammonium bromide were added. The reaction mixture was heated till reflux and kept at reflux, while stirring vigorously. The reaction was monitored with HPLC. After 4 days at reflux, the starting epoxide was completely converted. The mixture was cooled to room temperature. 10 ml of chloroform was added. The organic layer was washed with 3×20 ml of water, dried (Na2SO4), filtrated and evaporated to dryness. Residue: 226 mg (brown oil). Purification of the residue by column chromatography (Merck silica gel 60; eluens: heptane/ethyl acetate=1/1) afforded R-enantiomer of bicalutamide as a white/yellow solid material. Purified yield: 122 mg (43%). HPLC: 96.3% purity. HPLC (chiral column): 94.7% e.e. 1H and 13C NMR in agreement with R-bicalutamide
Name
sodium p-fluorobenzenesulfinate
Quantity
133 mg
Type
reactant
Reaction Step Two
[Compound]
Name
epoxide
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Three
Identifiers
|
REACTION_CXSMILES
|
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([C@:12]2([CH3:15])[CH2:14][O:13]2)=[O:11])=[CH:5][C:4]=1[C:16]([F:19])([F:18])[F:17])#[N:2].[Na].[F:21][C:22]1[CH:27]=[CH:26][C:25]([S:28]([O-:30])=[O:29])=[CH:24][CH:23]=1>C(Cl)(Cl)Cl.O.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:15][C:12]([OH:13])([C:10]([NH:9][C:6]1[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[C:4]([C:16]([F:19])([F:18])[F:17])[CH:5]=1)=[O:11])[CH2:14][S:28]([C:25]1[CH:24]=[CH:23][C:22]([F:21])=[CH:27][CH:26]=1)(=[O:30])=[O:29] |f:1.2,5.6,^1:19|
|
Inputs
Step One
|
Name
|
|
|
Quantity
|
180 mg
|
|
Type
|
reactant
|
|
Smiles
|
C(#N)C1=C(C=C(C=C1)NC(=O)[C@]1(OC1)C)C(F)(F)F
|
|
Name
|
|
|
Quantity
|
12 mL
|
|
Type
|
solvent
|
|
Smiles
|
C(Cl)(Cl)Cl
|
|
Name
|
|
|
Quantity
|
12 mL
|
|
Type
|
solvent
|
|
Smiles
|
O
|
Step Two
|
Name
|
sodium p-fluorobenzenesulfinate
|
|
Quantity
|
133 mg
|
|
Type
|
reactant
|
|
Smiles
|
[Na].FC1=CC=C(C=C1)S(=O)[O-]
|
|
Name
|
|
|
Quantity
|
107 mg
|
|
Type
|
catalyst
|
|
Smiles
|
[Br-].C(CCC)[N+](CCCC)(CCCC)CCCC
|
Step Three
[Compound]
|
Name
|
epoxide
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Four
|
Name
|
|
|
Quantity
|
10 mL
|
|
Type
|
solvent
|
|
Smiles
|
C(Cl)(Cl)Cl
|
Conditions
Temperature
|
Control Type
|
AMBIENT
|
Stirring
|
Type
|
CUSTOM
|
|
Details
|
while stirring vigorously
|
|
Rate
|
UNSPECIFIED
|
|
RPM
|
0
|
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
The reaction mixture was heated
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
till reflux
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
at reflux
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
After 4 days at reflux
|
|
Duration
|
4 d
|
WASH
|
Type
|
WASH
|
|
Details
|
The organic layer was washed with 3×20 ml of water
|
DRY_WITH_MATERIAL
|
Type
|
DRY_WITH_MATERIAL
|
|
Details
|
dried (Na2SO4)
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
filtrated
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
evaporated to dryness
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
Purification of the residue by column chromatography (Merck silica gel 60; eluens: heptane/ethyl acetate=1/1)
|
Outcomes
Product
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
CC(CS(=O)(=O)C=1C=CC(=CC1)F)(C(=O)NC=2C=CC(=C(C2)C(F)(F)F)C#N)O
|
Source
|
Source
|
Open Reaction Database (ORD) |
|
Description
|
The Open Reaction Database (ORD) is an open-access schema and infrastructure for structuring and sharing organic reaction data, including a centralized data repository. The ORD schema supports conventional and emerging technologies, from benchtop reactions to automated high-throughput experiments and flow chemistry. Our vision is that a consistent data representation and infrastructure to support data sharing will enable downstream applications that will greatly improve the state of the art with respect to computer-aided synthesis planning, reaction prediction, and other predictive chemistry tasks. |
Patent
US07186854B2
Procedure details
180 mg of the chiral epoxide of example 17 was dissolved in a mixture of 12 ml chloroform and 12 ml of water. 133 mg of sodium-p-fluorobenzenesulfinate and 107 mg of tetrabutylammonium bromide were added. The reaction mixture was heated till reflux and kept at reflux, while stirring vigorously. The reaction was monitored with HPLC. After 4 days at reflux, the starting epoxide was completely converted. The mixture was cooled to room temperature. 10 ml of chloroform was added. The organic layer was washed with 3×20 ml of water, dried (Na2SO4), filtrated and evaporated to dryness. Residue: 226 mg (brown oil). Purification of the residue by column chromatography (Merck silica gel 60; eluens: heptane/ethyl acetate=1/1) afforded R-enantiomer of bicalutamide as a white/yellow solid material. Purified yield: 122 mg (43%). HPLC: 96.3% purity. HPLC (chiral column): 94.7% e.e. 1H and 13C NMR in agreement with R-bicalutamide
Name
sodium p-fluorobenzenesulfinate
Quantity
133 mg
Type
reactant
Reaction Step Two
[Compound]
Name
epoxide
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Three
Identifiers
|
REACTION_CXSMILES
|
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([C@:12]2([CH3:15])[CH2:14][O:13]2)=[O:11])=[CH:5][C:4]=1[C:16]([F:19])([F:18])[F:17])#[N:2].[Na].[F:21][C:22]1[CH:27]=[CH:26][C:25]([S:28]([O-:30])=[O:29])=[CH:24][CH:23]=1>C(Cl)(Cl)Cl.O.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:15][C:12]([OH:13])([C:10]([NH:9][C:6]1[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[C:4]([C:16]([F:19])([F:18])[F:17])[CH:5]=1)=[O:11])[CH2:14][S:28]([C:25]1[CH:24]=[CH:23][C:22]([F:21])=[CH:27][CH:26]=1)(=[O:30])=[O:29] |f:1.2,5.6,^1:19|
|
Inputs
Step One
|
Name
|
|
|
Quantity
|
180 mg
|
|
Type
|
reactant
|
|
Smiles
|
C(#N)C1=C(C=C(C=C1)NC(=O)[C@]1(OC1)C)C(F)(F)F
|
|
Name
|
|
|
Quantity
|
12 mL
|
|
Type
|
solvent
|
|
Smiles
|
C(Cl)(Cl)Cl
|
|
Name
|
|
|
Quantity
|
12 mL
|
|
Type
|
solvent
|
|
Smiles
|
O
|
Step Two
|
Name
|
sodium p-fluorobenzenesulfinate
|
|
Quantity
|
133 mg
|
|
Type
|
reactant
|
|
Smiles
|
[Na].FC1=CC=C(C=C1)S(=O)[O-]
|
|
Name
|
|
|
Quantity
|
107 mg
|
|
Type
|
catalyst
|
|
Smiles
|
[Br-].C(CCC)[N+](CCCC)(CCCC)CCCC
|
Step Three
[Compound]
|
Name
|
epoxide
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Four
|
Name
|
|
|
Quantity
|
10 mL
|
|
Type
|
solvent
|
|
Smiles
|
C(Cl)(Cl)Cl
|
Conditions
Temperature
|
Control Type
|
AMBIENT
|
Stirring
|
Type
|
CUSTOM
|
|
Details
|
while stirring vigorously
|
|
Rate
|
UNSPECIFIED
|
|
RPM
|
0
|
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
The reaction mixture was heated
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
till reflux
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
at reflux
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
After 4 days at reflux
|
|
Duration
|
4 d
|
WASH
|
Type
|
WASH
|
|
Details
|
The organic layer was washed with 3×20 ml of water
|
DRY_WITH_MATERIAL
|
Type
|
DRY_WITH_MATERIAL
|
|
Details
|
dried (Na2SO4)
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
filtrated
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
evaporated to dryness
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
Purification of the residue by column chromatography (Merck silica gel 60; eluens: heptane/ethyl acetate=1/1)
|
Outcomes
Product
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
CC(CS(=O)(=O)C=1C=CC(=CC1)F)(C(=O)NC=2C=CC(=C(C2)C(F)(F)F)C#N)O
|
Source
|
Source
|
Open Reaction Database (ORD) |
|
Description
|
The Open Reaction Database (ORD) is an open-access schema and infrastructure for structuring and sharing organic reaction data, including a centralized data repository. The ORD schema supports conventional and emerging technologies, from benchtop reactions to automated high-throughput experiments and flow chemistry. Our vision is that a consistent data representation and infrastructure to support data sharing will enable downstream applications that will greatly improve the state of the art with respect to computer-aided synthesis planning, reaction prediction, and other predictive chemistry tasks. |
