Gefitinib-d3
Katalognummer B563487
Molekulargewicht: 449.926
InChI-Schlüssel: XGALLCVXEZPNRQ-FIBGUPNXSA-N
Achtung: Nur für Forschungszwecke. Nicht für den menschlichen oder tierärztlichen Gebrauch.
Patent
US08350029B2
Procedure details
Methanol (1200 ml) and 6-(3-morpholino propoxy)-7-methoxy-4-chloro quinazoline (200 gm) were stirred for 15 minutes at 25-30° C., then a solution of 4-fluoro-3-chloroaniline in methanol (213 gm in 400 ml) was charged and refluxed for 6 hours. The reaction mass was cooled to 15-20° C., hydrochloric acid (40 ml) was added drop wise, and stirred at 5-10° C. for 30 minutes. The solid obtained was filtered and washed with chilled methanol (150 ml). The solid was dissolved in a mixture of toluene (30 volume) and methanol (5 volume), the reaction mass was concentrated to half the volume and cooled to 5-10° C. The solid obtained was filtered, washed with toluene (200 ml) and dried at 45-50° C. to yield the title compound (183 gm, 70% yield).
Quantity
200 g
Type
reactant
Reaction Step Three
Name
Yield
70%
Identifiers
|
REACTION_CXSMILES
|
[O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][C:20]=2[O:21][CH3:22])[N:17]=[CH:16][N:15]=[C:14]3Cl)[CH2:3][CH2:2]1.[F:24][C:25]1[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][C:26]=1[Cl:32].Cl>CO>[Cl:32][C:26]1[CH:27]=[C:28]([CH:30]=[CH:31][C:25]=1[F:24])[NH:29][C:14]1[C:13]2[C:18](=[CH:19][C:20]([O:21][CH3:22])=[C:11]([O:10][CH2:9][CH2:8][CH2:7][N:4]3[CH2:5][CH2:6][O:1][CH2:2][CH2:3]3)[CH:12]=2)[N:17]=[CH:16][N:15]=1
|
Inputs
Step One
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
FC1=C(C=C(N)C=C1)Cl
|
|
Name
|
|
|
Quantity
|
400 mL
|
|
Type
|
solvent
|
|
Smiles
|
CO
|
Step Two
|
Name
|
|
|
Quantity
|
40 mL
|
|
Type
|
reactant
|
|
Smiles
|
Cl
|
Step Three
|
Name
|
|
|
Quantity
|
200 g
|
|
Type
|
reactant
|
|
Smiles
|
O1CCN(CC1)CCCOC=1C=C2C(=NC=NC2=CC1OC)Cl
|
|
Name
|
|
|
Quantity
|
1200 mL
|
|
Type
|
solvent
|
|
Smiles
|
CO
|
Conditions
Temperature
|
Control Type
|
UNSPECIFIED
|
|
Setpoint
|
17.5 (± 2.5) °C
|
Stirring
|
Type
|
CUSTOM
|
|
Details
|
stirred at 5-10° C. for 30 minutes
|
|
Rate
|
UNSPECIFIED
|
|
RPM
|
0
|
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
refluxed for 6 hours
|
|
Duration
|
6 h
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The solid obtained
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
was filtered
|
WASH
|
Type
|
WASH
|
|
Details
|
washed with chilled methanol (150 ml)
|
DISSOLUTION
|
Type
|
DISSOLUTION
|
|
Details
|
The solid was dissolved in a mixture of toluene (30 volume) and methanol (5 volume)
|
CONCENTRATION
|
Type
|
CONCENTRATION
|
|
Details
|
the reaction mass was concentrated to half the volume
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
cooled to 5-10° C
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The solid obtained
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
was filtered
|
WASH
|
Type
|
WASH
|
|
Details
|
washed with toluene (200 ml)
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
dried at 45-50° C.
|
Outcomes
Product
Details
Reaction Time |
30 min |
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
ClC=1C=C(NC2=NC=NC3=CC(=C(C=C23)OCCCN2CCOCC2)OC)C=CC1F
|
Measurements
| Type | Value | Analysis |
|---|---|---|
| AMOUNT: MASS | 183 g | |
| YIELD: PERCENTYIELD | 70% |
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
US08350029B2
Procedure details
Methanol (1200 ml) and 6-(3-morpholino propoxy)-7-methoxy-4-chloro quinazoline (200 gm) were stirred for 15 minutes at 25-30° C., then a solution of 4-fluoro-3-chloroaniline in methanol (213 gm in 400 ml) was charged and refluxed for 6 hours. The reaction mass was cooled to 15-20° C., hydrochloric acid (40 ml) was added drop wise, and stirred at 5-10° C. for 30 minutes. The solid obtained was filtered and washed with chilled methanol (150 ml). The solid was dissolved in a mixture of toluene (30 volume) and methanol (5 volume), the reaction mass was concentrated to half the volume and cooled to 5-10° C. The solid obtained was filtered, washed with toluene (200 ml) and dried at 45-50° C. to yield the title compound (183 gm, 70% yield).
Quantity
200 g
Type
reactant
Reaction Step Three
Name
Yield
70%
Identifiers
|
REACTION_CXSMILES
|
[O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][C:20]=2[O:21][CH3:22])[N:17]=[CH:16][N:15]=[C:14]3Cl)[CH2:3][CH2:2]1.[F:24][C:25]1[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][C:26]=1[Cl:32].Cl>CO>[Cl:32][C:26]1[CH:27]=[C:28]([CH:30]=[CH:31][C:25]=1[F:24])[NH:29][C:14]1[C:13]2[C:18](=[CH:19][C:20]([O:21][CH3:22])=[C:11]([O:10][CH2:9][CH2:8][CH2:7][N:4]3[CH2:5][CH2:6][O:1][CH2:2][CH2:3]3)[CH:12]=2)[N:17]=[CH:16][N:15]=1
|
Inputs
Step One
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
FC1=C(C=C(N)C=C1)Cl
|
|
Name
|
|
|
Quantity
|
400 mL
|
|
Type
|
solvent
|
|
Smiles
|
CO
|
Step Two
|
Name
|
|
|
Quantity
|
40 mL
|
|
Type
|
reactant
|
|
Smiles
|
Cl
|
Step Three
|
Name
|
|
|
Quantity
|
200 g
|
|
Type
|
reactant
|
|
Smiles
|
O1CCN(CC1)CCCOC=1C=C2C(=NC=NC2=CC1OC)Cl
|
|
Name
|
|
|
Quantity
|
1200 mL
|
|
Type
|
solvent
|
|
Smiles
|
CO
|
Conditions
Temperature
|
Control Type
|
UNSPECIFIED
|
|
Setpoint
|
17.5 (± 2.5) °C
|
Stirring
|
Type
|
CUSTOM
|
|
Details
|
stirred at 5-10° C. for 30 minutes
|
|
Rate
|
UNSPECIFIED
|
|
RPM
|
0
|
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
refluxed for 6 hours
|
|
Duration
|
6 h
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The solid obtained
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
was filtered
|
WASH
|
Type
|
WASH
|
|
Details
|
washed with chilled methanol (150 ml)
|
DISSOLUTION
|
Type
|
DISSOLUTION
|
|
Details
|
The solid was dissolved in a mixture of toluene (30 volume) and methanol (5 volume)
|
CONCENTRATION
|
Type
|
CONCENTRATION
|
|
Details
|
the reaction mass was concentrated to half the volume
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
cooled to 5-10° C
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The solid obtained
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
was filtered
|
WASH
|
Type
|
WASH
|
|
Details
|
washed with toluene (200 ml)
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
dried at 45-50° C.
|
Outcomes
Product
Details
Reaction Time |
30 min |
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
ClC=1C=C(NC2=NC=NC3=CC(=C(C=C23)OCCCN2CCOCC2)OC)C=CC1F
|
Measurements
| Type | Value | Analysis |
|---|---|---|
| AMOUNT: MASS | 183 g | |
| YIELD: PERCENTYIELD | 70% |
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. |
