![molecular formula C26H23FIN5O4 B1429255 N-(3-(3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidin-5-ylamino)phenyl)acetamide CAS No. 871700-25-3](/img/structure/B1429255.png)
N-(3-(3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidin-5-ylamino)phenyl)acetamide
货号 B1429255
分子量: 615.4 g/mol
InChI 键: VUCVSBZRQBGJPT-UHFFFAOYSA-N
注意: 仅供研究使用。不适用于人类或兽医用途。
Patent
US09181243B2
Procedure details
Under a nitrogen atmosphere, tetrahydrofuran (40 mL) was added to N-{3-[3-cyclopropyl-1-(2-fluoro-4-iodo-phenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-ylamino]-phenyl}-acetamide (5 g) and a methanol solution (1.57 g) containing 28% sodium methoxide was added and the mixture was stirred at room temperature for 4 hours. Acetic acid (0.56 mL) was added to the mixture and the mixture was stirred at room temperature for 30 min. And then water (40 mL) was added and the mixture was further stirred for 1 hour. The crystals were collected by filtration and dried under reduced pressure at 40° C. to give trametinib (4.75 g). Its HPLC content of A impurity is 0.42 wt %.
Quantity
5 g
Type
reactant
Reaction Step One
Name
sodium methoxide
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Two
Name
Identifiers
|
REACTION_CXSMILES
|
O1CCCC1.[CH:6]1([N:9]2[C:14](=[O:15])[C:13]3[C:16]([NH:23][C:24]4[CH:25]=[C:26]([NH:30][C:31](=[O:33])[CH3:32])[CH:27]=[CH:28][CH:29]=4)=[C:17]([CH3:22])[C:18](=[O:21])[N:19]([CH3:20])[C:12]=3[N:11]([C:34]3[CH:39]=[CH:38][C:37]([I:40])=[CH:36][C:35]=3[F:41])[C:10]2=[O:42])[CH2:8][CH2:7]1.CO.C[O-].[Na+]>O.C(O)(=O)C>[CH3:22][C:17]1[C:18](=[O:21])[N:19]([CH3:20])[C:12]([NH:11][C:34]2[CH:39]=[CH:38][C:37]([I:40])=[CH:36][C:35]=2[F:41])=[C:13]2[C:14]([N:9]([CH:6]3[CH2:8][CH2:7]3)[C:10]([N:23]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([NH:30][C:31]([CH3:32])=[O:33])[CH:25]=3)[C:16]=12)=[O:42])=[O:15] |f:3.4|
|
Inputs
Step One
|
Name
|
|
|
Quantity
|
40 mL
|
|
Type
|
reactant
|
|
Smiles
|
O1CCCC1
|
|
Name
|
|
|
Quantity
|
5 g
|
|
Type
|
reactant
|
|
Smiles
|
C1(CC1)N1C(N(C2=C(C1=O)C(=C(C(N2C)=O)C)NC=2C=C(C=CC2)NC(C)=O)C2=C(C=C(C=C2)I)F)=O
|
Step Two
|
Name
|
|
|
Quantity
|
1.57 g
|
|
Type
|
reactant
|
|
Smiles
|
CO
|
|
Name
|
sodium methoxide
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
C[O-].[Na+]
|
Step Three
|
Name
|
|
|
Quantity
|
40 mL
|
|
Type
|
solvent
|
|
Smiles
|
O
|
Step Four
|
Name
|
|
|
Quantity
|
0.56 mL
|
|
Type
|
solvent
|
|
Smiles
|
C(C)(=O)O
|
Conditions
Temperature
|
Control Type
|
AMBIENT
|
Stirring
|
Type
|
CUSTOM
|
|
Details
|
the mixture was stirred at room temperature for 4 hours
|
|
Rate
|
UNSPECIFIED
|
|
RPM
|
0
|
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
ADDITION
|
Type
|
ADDITION
|
|
Details
|
was added
|
STIRRING
|
Type
|
STIRRING
|
|
Details
|
the mixture was stirred at room temperature for 30 min
|
|
Duration
|
30 min
|
STIRRING
|
Type
|
STIRRING
|
|
Details
|
the mixture was further stirred for 1 hour
|
|
Duration
|
1 h
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
The crystals were collected by filtration
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
dried under reduced pressure at 40° C.
|
Outcomes
Product
Details
Reaction Time |
4 h |
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
CC1=C2C(=C(N(C1=O)C)NC=3C=CC(=CC3F)I)C(=O)N(C(=O)N2C=4C=CC=C(C4)NC(=O)C)C5CC5
|
Measurements
| Type | Value | Analysis |
|---|---|---|
| AMOUNT: MASS | 4.75 g | |
| YIELD: CALCULATEDPERCENTYIELD | 95% |
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. |
