Erlotinib
Número de catálogo B000232
Peso molecular: 393.4 g/mol
Clave InChI: AAKJLRGGTJKAMG-UHFFFAOYSA-N
Atención: Solo para uso de investigación. No para uso humano o veterinario.
Patent
US08669265B2
Procedure details
Crude erlotinib hydrochloride (37 gm, obtained in reference example 1), water (370 ml) and chloroform (370 ml) are taken into a reaction flask at 25-30° C. and start stirring. The contents are heated to 5-55° C., sodium hydroxide solution is added at 50-55° C. and then stirred for 15 minutes at 50° C. (clear solution not observed). To the reaction mass added chloroform (200 ml) and methanol (60 ml) and stirred for 15 minutes at 50° C. (clear solution observed). Separated the layers at 50° C., the organic layer is washed with water (200 ml) at 50° C. and then combined the organic layers. To the organic layer added methanol (60 ml) dried over sodium sulfate and distilled the total solvent under vacuum at 50-55° C. To the residue added n-heptane (300 ml) and stirred for 30 minutes at 25-30° C. Filtered the material, washed with n-heptane (70 ml) and then dried the material at 60-65° C. under vacuum for 3 hours 30 minutes to give 34 gm of anhydrous erlotinib free base (HPLC Purity: 98.2%, Moisture Content: 0.2%).
Name
erlotinib hydrochloride
Quantity
37 g
Type
reactant
Reaction Step One
Name
Yield
0.2%
Identifiers
|
REACTION_CXSMILES
|
[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:20]([NH:21][C:22]3[CH:23]=[CH:24][CH:25]=[C:26]([C:28]#[CH:29])[CH:27]=3)=[N:19][CH:18]=[N:17][C:9]2=[CH:10][C:11]=1[O:12][CH2:13][CH2:14][O:15][CH3:16].Cl.O.C(Cl)(Cl)Cl.[OH-].[Na+]>CO>[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:20]([NH:21][C:22]3[CH:23]=[CH:24][CH:25]=[C:26]([C:28]#[CH:29])[CH:27]=3)=[N:19][CH:18]=[N:17][C:9]2=[CH:10][C:11]=1[O:12][CH2:13][CH2:14][O:15][CH3:16] |f:0.1,4.5|
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Inputs
Step One
|
Name
|
erlotinib hydrochloride
|
|
Quantity
|
37 g
|
|
Type
|
reactant
|
|
Smiles
|
COCCOC=1C=C2C(=CC1OCCOC)N=CN=C2NC=3C=CC=C(C3)C#C.Cl
|
|
Name
|
|
|
Quantity
|
370 mL
|
|
Type
|
reactant
|
|
Smiles
|
O
|
|
Name
|
|
|
Quantity
|
370 mL
|
|
Type
|
reactant
|
|
Smiles
|
C(Cl)(Cl)Cl
|
Step Two
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
[OH-].[Na+]
|
Step Three
|
Name
|
|
|
Quantity
|
200 mL
|
|
Type
|
reactant
|
|
Smiles
|
C(Cl)(Cl)Cl
|
|
Name
|
|
|
Quantity
|
60 mL
|
|
Type
|
solvent
|
|
Smiles
|
CO
|
Conditions
Temperature
|
Control Type
|
UNSPECIFIED
|
|
Setpoint
|
30 (± 25) °C
|
Stirring
|
Type
|
CUSTOM
|
|
Details
|
start stirring
|
|
Rate
|
UNSPECIFIED
|
|
RPM
|
0
|
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
STIRRING
|
Type
|
STIRRING
|
|
Details
|
stirred for 15 minutes at 50° C. (clear solution not
|
|
Duration
|
15 min
|
STIRRING
|
Type
|
STIRRING
|
|
Details
|
stirred for 15 minutes at 50° C. (clear solution observed)
|
|
Duration
|
15 min
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
Separated the layers at 50° C.
|
WASH
|
Type
|
WASH
|
|
Details
|
the organic layer is washed with water (200 ml) at 50° C.
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
To the organic layer added methanol (60 ml)
|
DRY_WITH_MATERIAL
|
Type
|
DRY_WITH_MATERIAL
|
|
Details
|
dried over sodium sulfate
|
DISTILLATION
|
Type
|
DISTILLATION
|
|
Details
|
distilled the total solvent under vacuum at 50-55° C
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
To the residue added n-heptane (300 ml)
|
STIRRING
|
Type
|
STIRRING
|
|
Details
|
stirred for 30 minutes at 25-30° C
|
|
Duration
|
30 min
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
Filtered the material
|
WASH
|
Type
|
WASH
|
|
Details
|
washed with n-heptane (70 ml)
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
dried the material at 60-65° C. under vacuum for 3 hours 30 minutes
|
|
Duration
|
30 min
|
Outcomes
Product
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
COCCOC=1C=C2C(=CC1OCCOC)N=CN=C2NC=3C=CC=C(C3)C#C
|
Measurements
| Type | Value | Analysis |
|---|---|---|
| AMOUNT: MASS | 34 g | |
| YIELD: PERCENTYIELD | 0.2% | |
| YIELD: CALCULATEDPERCENTYIELD | 100.4% |
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. |
