Osimertinib D6
Número de catálogo B2766964
Peso molecular: 505.656
Clave InChI: DUYJMQONPNNFPI-XERRXZQWSA-N
Atención: Solo para uso de investigación. No para uso humano o veterinario.
Patent
US08946235B2
Procedure details
To a stirred solution of 3-chloro-N-[2-[2-dimethylaminoethyl(methyl)amino]-4-methoxy-5-[[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino]phenyl]propanamide (Intermediate 174, 31.5 g, 58.76 mmol) in acetonitrile (310 mL) was added triethylamine (17.84 g, 176.28 mmol) at r.t. The resulting mixture was heated to 80° C. for 6 h then cooled to r.t. Water (130 mL) was then added and the mixture stirred for 12 h. The mixture was then filtered, washed with a mixture of water and acetonitrile (160 mL, 1:1) and dried at 50° C. for overnight to give the title compound (19.2 g, 94%) as a solid form identified herein as polymorphic form D. 1H NMR: 2.69 (3H, s), 2.83 (6H, d), 3.35 (4H, s), 3.84 (3H, s), 3.91 (3H, s), 5.75 (1H, d), 6.28 (1H, d), 6.67 (1H, dd), 7.05-7.23 (2H, m), 7.29 (1H, t), 7.43 (1H, d), 7.56 (1H, d), 8.21 (2H, s), 8.81 (1H, s), 9.47 (1H, s), 9.52 (1H, s), m/z: ES+ MH+ 500.26.
Quantity
31.5 g
Type
reactant
Reaction Step One
Name
Yield
94%
Identifiers
|
REACTION_CXSMILES
|
Cl[CH2:2][CH2:3][C:4]([NH:6][C:7]1[CH:12]=[C:11]([NH:13][C:14]2[N:19]=[C:18]([C:20]3[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[N:22]([CH3:29])[CH:21]=3)[CH:17]=[CH:16][N:15]=2)[C:10]([O:30][CH3:31])=[CH:9][C:8]=1[N:32]([CH2:34][CH2:35][N:36]([CH3:38])[CH3:37])[CH3:33])=[O:5].C(N(CC)CC)C.O>C(#N)C>[CH3:38][N:36]([CH3:37])[CH2:35][CH2:34][N:32]([CH3:33])[C:8]1[CH:9]=[C:10]([O:30][CH3:31])[C:11]([NH:13][C:14]2[N:19]=[C:18]([C:20]3[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[N:22]([CH3:29])[CH:21]=3)[CH:17]=[CH:16][N:15]=2)=[CH:12][C:7]=1[NH:6][C:4](=[O:5])[CH:3]=[CH2:2]
|
Inputs
Step One
|
Name
|
|
|
Quantity
|
31.5 g
|
|
Type
|
reactant
|
|
Smiles
|
ClCCC(=O)NC1=C(C=C(C(=C1)NC1=NC=CC(=N1)C1=CN(C2=CC=CC=C12)C)OC)N(C)CCN(C)C
|
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
ClCCC(=O)NC1=C(C=C(C(=C1)NC1=NC=CC(=N1)C1=CN(C2=CC=CC=C12)C)OC)N(C)CCN(C)C
|
|
Name
|
|
|
Quantity
|
17.84 g
|
|
Type
|
reactant
|
|
Smiles
|
C(C)N(CC)CC
|
|
Name
|
|
|
Quantity
|
310 mL
|
|
Type
|
solvent
|
|
Smiles
|
C(C)#N
|
Step Two
|
Name
|
|
|
Quantity
|
130 mL
|
|
Type
|
reactant
|
|
Smiles
|
O
|
Conditions
Temperature
|
Control Type
|
UNSPECIFIED
|
|
Setpoint
|
80 °C
|
Stirring
|
Type
|
CUSTOM
|
|
Details
|
the mixture stirred for 12 h
|
|
Rate
|
UNSPECIFIED
|
|
RPM
|
0
|
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
then cooled to r.t
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
The mixture was then filtered
|
WASH
|
Type
|
WASH
|
|
Details
|
washed with a mixture of water and acetonitrile (160 mL, 1:1)
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
dried at 50° C. for overnight
|
|
Duration
|
8 (± 8) h
|
Outcomes
Product
Details
Reaction Time |
12 h |
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
CN(CCN(C1=C(C=C(C(=C1)OC)NC1=NC=CC(=N1)C1=CN(C2=CC=CC=C12)C)NC(C=C)=O)C)C
|
Measurements
| Type | Value | Analysis |
|---|---|---|
| AMOUNT: MASS | 19.2 g | |
| YIELD: PERCENTYIELD | 94% | |
| YIELD: CALCULATEDPERCENTYIELD | 65.4% |
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. |
Patent
US08946235B2
Procedure details
To a stirred solution of 3-chloro-N-[2-[2-dimethylaminoethyl(methyl)amino]-4-methoxy-5-[[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino]phenyl]propanamide (Intermediate 174, 31.5 g, 58.76 mmol) in acetonitrile (310 mL) was added triethylamine (17.84 g, 176.28 mmol) at r.t. The resulting mixture was heated to 80° C. for 6 h then cooled to r.t. Water (130 mL) was then added and the mixture stirred for 12 h. The mixture was then filtered, washed with a mixture of water and acetonitrile (160 mL, 1:1) and dried at 50° C. for overnight to give the title compound (19.2 g, 94%) as a solid form identified herein as polymorphic form D. 1H NMR: 2.69 (3H, s), 2.83 (6H, d), 3.35 (4H, s), 3.84 (3H, s), 3.91 (3H, s), 5.75 (1H, d), 6.28 (1H, d), 6.67 (1H, dd), 7.05-7.23 (2H, m), 7.29 (1H, t), 7.43 (1H, d), 7.56 (1H, d), 8.21 (2H, s), 8.81 (1H, s), 9.47 (1H, s), 9.52 (1H, s), m/z: ES+ MH+ 500.26.
Quantity
31.5 g
Type
reactant
Reaction Step One
Name
Yield
94%
Identifiers
|
REACTION_CXSMILES
|
Cl[CH2:2][CH2:3][C:4]([NH:6][C:7]1[CH:12]=[C:11]([NH:13][C:14]2[N:19]=[C:18]([C:20]3[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[N:22]([CH3:29])[CH:21]=3)[CH:17]=[CH:16][N:15]=2)[C:10]([O:30][CH3:31])=[CH:9][C:8]=1[N:32]([CH2:34][CH2:35][N:36]([CH3:38])[CH3:37])[CH3:33])=[O:5].C(N(CC)CC)C.O>C(#N)C>[CH3:38][N:36]([CH3:37])[CH2:35][CH2:34][N:32]([CH3:33])[C:8]1[CH:9]=[C:10]([O:30][CH3:31])[C:11]([NH:13][C:14]2[N:19]=[C:18]([C:20]3[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[N:22]([CH3:29])[CH:21]=3)[CH:17]=[CH:16][N:15]=2)=[CH:12][C:7]=1[NH:6][C:4](=[O:5])[CH:3]=[CH2:2]
|
Inputs
Step One
|
Name
|
|
|
Quantity
|
31.5 g
|
|
Type
|
reactant
|
|
Smiles
|
ClCCC(=O)NC1=C(C=C(C(=C1)NC1=NC=CC(=N1)C1=CN(C2=CC=CC=C12)C)OC)N(C)CCN(C)C
|
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
ClCCC(=O)NC1=C(C=C(C(=C1)NC1=NC=CC(=N1)C1=CN(C2=CC=CC=C12)C)OC)N(C)CCN(C)C
|
|
Name
|
|
|
Quantity
|
17.84 g
|
|
Type
|
reactant
|
|
Smiles
|
C(C)N(CC)CC
|
|
Name
|
|
|
Quantity
|
310 mL
|
|
Type
|
solvent
|
|
Smiles
|
C(C)#N
|
Step Two
|
Name
|
|
|
Quantity
|
130 mL
|
|
Type
|
reactant
|
|
Smiles
|
O
|
Conditions
Temperature
|
Control Type
|
UNSPECIFIED
|
|
Setpoint
|
80 °C
|
Stirring
|
Type
|
CUSTOM
|
|
Details
|
the mixture stirred for 12 h
|
|
Rate
|
UNSPECIFIED
|
|
RPM
|
0
|
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
then cooled to r.t
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
The mixture was then filtered
|
WASH
|
Type
|
WASH
|
|
Details
|
washed with a mixture of water and acetonitrile (160 mL, 1:1)
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
dried at 50° C. for overnight
|
|
Duration
|
8 (± 8) h
|
Outcomes
Product
Details
Reaction Time |
12 h |
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
CN(CCN(C1=C(C=C(C(=C1)OC)NC1=NC=CC(=N1)C1=CN(C2=CC=CC=C12)C)NC(C=C)=O)C)C
|
Measurements
| Type | Value | Analysis |
|---|---|---|
| AMOUNT: MASS | 19.2 g | |
| YIELD: PERCENTYIELD | 94% | |
| YIELD: CALCULATEDPERCENTYIELD | 65.4% |
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. |
