Nevirapine-D4
Katalognummer B3026168
Molekulargewicht: 270.32 g/mol
InChI-Schlüssel: NQDJXKOVJZTUJA-CQOLUAMGSA-N
Achtung: Nur für Forschungszwecke. Nicht für den menschlichen oder tierärztlichen Gebrauch.
Patent
US05569760
Procedure details
The process according to claim 4, wherein 2-chloro-N-(2-chloro-4-methyl-3-pyridyl)-3-pyridine carboxamide is heated with cyclopropylamine in the presence of 1 to 2 mol of calcium oxide in diglyme to 135° to 145° C. for 6 to 7 hours, the reaction mixture is then cooled down to 20° to 30° C. and filtered, the filter cake is washed with diglyme and the combined filtrates are concentrated, the residue is then diluted with diglyme and this solution is added to a solution or suspension of sodium hydride in diglyme, heated to 130° to 140° C., and the reaction mixture is kept at a temperature of 130° to 140° C. for 30 minutes to one hour and then the reaction medium is distilled off, the residue is hydrolysed at a temperature of 50° to 80° C. and then cooled to a temperature of about 25° C. and mixed with an inert solvent and an organic acid and the reaction mixture is stirred for about 1 hour at 10° to 25° C., the resultant suspension of the product is separated, washed with an inert solvent, followed by water and alcohol to give nevirapine.
Quantity
0 (± 1) mol
Type
reactant
Reaction Step One
Identifiers
|
REACTION_CXSMILES
|
Cl[C:2]1[C:7]([C:8]([NH:10][C:11]2[C:12](Cl)=[N:13][CH:14]=[CH:15][C:16]=2[CH3:17])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[CH:19]1([NH2:22])[CH2:21][CH2:20]1.[O-2].[Ca+2]>COCCOCCOC>[CH3:17][C:16]1[CH:15]=[CH:14][N:13]=[C:12]2[N:22]([CH:19]3[CH2:21][CH2:20]3)[C:2]3[N:3]=[CH:4][CH:5]=[CH:6][C:7]=3[C:8](=[O:9])[NH:10][C:11]=12 |f:2.3|
|
Inputs
Step One
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
ClC1=NC=CC=C1C(=O)NC=1C(=NC=CC1C)Cl
|
Step Two
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
C1(CC1)N
|
|
Name
|
|
|
Quantity
|
1.5 (± 0.5) mol
|
|
Type
|
reactant
|
|
Smiles
|
[O-2].[Ca+2]
|
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
COCCOCCOC
|
Conditions
Temperature
|
Control Type
|
UNSPECIFIED
|
|
Setpoint
|
25 °C
|
Stirring
|
Type
|
CUSTOM
|
|
Details
|
an organic acid and the reaction mixture is stirred for about 1 hour at 10° to 25° C.
|
|
Rate
|
UNSPECIFIED
|
|
RPM
|
0
|
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
the reaction mixture is then cooled down to 20° to 30° C.
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
filtered
|
WASH
|
Type
|
WASH
|
|
Details
|
the filter cake is washed with diglyme
|
CONCENTRATION
|
Type
|
CONCENTRATION
|
|
Details
|
the combined filtrates are concentrated
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
the residue is then diluted with diglyme
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
this solution is added to a solution or suspension of sodium hydride in diglyme
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
heated to 130° to 140° C.
|
WAIT
|
Type
|
WAIT
|
|
Details
|
the reaction mixture is kept at a temperature of 130° to 140° C. for 30 minutes to one hour
|
DISTILLATION
|
Type
|
DISTILLATION
|
|
Details
|
the reaction medium is distilled off
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
is hydrolysed at a temperature of 50° to 80° C.
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
mixed with an inert solvent
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
the resultant suspension of the product
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
is separated
|
WASH
|
Type
|
WASH
|
|
Details
|
washed with an inert solvent
|
Outcomes
Product
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
US05569760
Procedure details
The process according to claim 4, wherein 2-chloro-N-(2-chloro-4-methyl-3-pyridyl)-3-pyridine carboxamide is heated with cyclopropylamine in the presence of 1 to 2 mol of calcium oxide in diglyme to 135° to 145° C. for 6 to 7 hours, the reaction mixture is then cooled down to 20° to 30° C. and filtered, the filter cake is washed with diglyme and the combined filtrates are concentrated, the residue is then diluted with diglyme and this solution is added to a solution or suspension of sodium hydride in diglyme, heated to 130° to 140° C., and the reaction mixture is kept at a temperature of 130° to 140° C. for 30 minutes to one hour and then the reaction medium is distilled off, the residue is hydrolysed at a temperature of 50° to 80° C. and then cooled to a temperature of about 25° C. and mixed with an inert solvent and an organic acid and the reaction mixture is stirred for about 1 hour at 10° to 25° C., the resultant suspension of the product is separated, washed with an inert solvent, followed by water and alcohol to give nevirapine.
Quantity
0 (± 1) mol
Type
reactant
Reaction Step One
Identifiers
|
REACTION_CXSMILES
|
Cl[C:2]1[C:7]([C:8]([NH:10][C:11]2[C:12](Cl)=[N:13][CH:14]=[CH:15][C:16]=2[CH3:17])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[CH:19]1([NH2:22])[CH2:21][CH2:20]1.[O-2].[Ca+2]>COCCOCCOC>[CH3:17][C:16]1[CH:15]=[CH:14][N:13]=[C:12]2[N:22]([CH:19]3[CH2:21][CH2:20]3)[C:2]3[N:3]=[CH:4][CH:5]=[CH:6][C:7]=3[C:8](=[O:9])[NH:10][C:11]=12 |f:2.3|
|
Inputs
Step One
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
ClC1=NC=CC=C1C(=O)NC=1C(=NC=CC1C)Cl
|
Step Two
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
C1(CC1)N
|
|
Name
|
|
|
Quantity
|
1.5 (± 0.5) mol
|
|
Type
|
reactant
|
|
Smiles
|
[O-2].[Ca+2]
|
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
COCCOCCOC
|
Conditions
Temperature
|
Control Type
|
UNSPECIFIED
|
|
Setpoint
|
25 °C
|
Stirring
|
Type
|
CUSTOM
|
|
Details
|
an organic acid and the reaction mixture is stirred for about 1 hour at 10° to 25° C.
|
|
Rate
|
UNSPECIFIED
|
|
RPM
|
0
|
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
the reaction mixture is then cooled down to 20° to 30° C.
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
filtered
|
WASH
|
Type
|
WASH
|
|
Details
|
the filter cake is washed with diglyme
|
CONCENTRATION
|
Type
|
CONCENTRATION
|
|
Details
|
the combined filtrates are concentrated
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
the residue is then diluted with diglyme
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
this solution is added to a solution or suspension of sodium hydride in diglyme
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
heated to 130° to 140° C.
|
WAIT
|
Type
|
WAIT
|
|
Details
|
the reaction mixture is kept at a temperature of 130° to 140° C. for 30 minutes to one hour
|
DISTILLATION
|
Type
|
DISTILLATION
|
|
Details
|
the reaction medium is distilled off
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
is hydrolysed at a temperature of 50° to 80° C.
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
mixed with an inert solvent
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
the resultant suspension of the product
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
is separated
|
WASH
|
Type
|
WASH
|
|
Details
|
washed with an inert solvent
|
Outcomes
Product
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. |
