![molecular formula C14H14ClF5N4O2S B8278460 4-(2-Chloro-2,2-difluoroethyl)-1-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}pyrrolidin-2-one](/img/structure/B8278460.png)
4-(2-Chloro-2,2-difluoroethyl)-1-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}pyrrolidin-2-one
カタログ番号 B8278460
分子量: 432.8 g/mol
InChIキー: DCXFIOLWWRXEQH-UHFFFAOYSA-N
注意: 研究専用です。人間または獣医用ではありません。
Patent
US08822508B2
Procedure details
To a hot solution (80° C.) of ZnCl2 (0.23 g, 1.69 mmol, 10 mol %) and 2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazole a28 (4 g, 16.96 mmol) in dioxane (200 ml) is added a solution of 4-(2-chloro-2,2-difluoroethyl)-1-(chloromethyl)pyrrolidin-2-one a18 in dioxane (5 ml). The reaction mixture is heated at 85° C. for 5 days, then a further 2 g of pyrrolidinone a18 is added in one portion and the reaction mixture is kept under agitation at 90° C. for 1 day. A further addition of pyrrolidinone a18 (2 g) in order to insure complete conversion of compound a28 and further heating of the reaction mixture at reflux for 3 days increased significatively the conversion of imidazo[2,1-b][1,3,4]thiadiazole a28. After cooling and hydrolysis (250 ml of water), the crude mixture is extracted by CH2Cl2 (2×250 ml). The cumulated organic layers are dried over MgSO4, filtered and condensed under reduced pressure. The residue is purified over silicagel (eluent: CH2Cl2/MeOH/NH4OH 99/1/0.1) to afford 4-(2-chloro-2,2-difluoroethyl)-1-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}pyrrolidin-2-one 4.
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Four
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Four
Identifiers
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REACTION_CXSMILES
|
[CH3:1][O:2][CH2:3][C:4]1[S:8][C:7]2=[N:9][C:10]([C:12]([F:15])([F:14])[F:13])=[CH:11][N:6]2[N:5]=1.[Cl:16][C:17]([F:28])([F:27])[CH2:18][CH:19]1[CH2:23][N:22]([CH2:24]Cl)[C:21](=[O:26])[CH2:20]1.N1CCCC1=O.S1C=NN2C=CN=C12>O1CCOCC1.[Cl-].[Cl-].[Zn+2].O>[Cl:16][C:17]([F:27])([F:28])[CH2:18][CH:19]1[CH2:23][N:22]([CH2:24][C:11]2[N:6]3[C:7]([S:8][C:4]([CH2:3][O:2][CH3:1])=[N:5]3)=[N:9][C:10]=2[C:12]([F:15])([F:13])[F:14])[C:21](=[O:26])[CH2:20]1 |f:5.6.7|
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Inputs
Step One
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Name
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|
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Quantity
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2 g
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Type
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reactant
|
|
Smiles
|
N1C(CCC1)=O
|
Step Two
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Name
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|
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Quantity
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0 (± 1) mol
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Type
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reactant
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Smiles
|
N1C(CCC1)=O
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Step Three
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Name
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Quantity
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0 (± 1) mol
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Type
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reactant
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Smiles
|
S1C=2N(N=C1)C=CN2
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Step Four
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Name
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Quantity
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0 (± 1) mol
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Type
|
reactant
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Smiles
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COCC1=NN2C(S1)=NC(=C2)C(F)(F)F
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Name
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|
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Quantity
|
0 (± 1) mol
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Type
|
reactant
|
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Smiles
|
ClC(CC1CC(N(C1)CCl)=O)(F)F
|
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Name
|
|
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Quantity
|
200 mL
|
|
Type
|
solvent
|
|
Smiles
|
O1CCOCC1
|
|
Name
|
|
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Quantity
|
5 mL
|
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Type
|
solvent
|
|
Smiles
|
O1CCOCC1
|
|
Name
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|
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Quantity
|
0.23 g
|
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Type
|
catalyst
|
|
Smiles
|
[Cl-].[Cl-].[Zn+2]
|
Step Five
|
Name
|
|
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Quantity
|
250 mL
|
|
Type
|
solvent
|
|
Smiles
|
O
|
Conditions
Temperature
|
Control Type
|
UNSPECIFIED
|
|
Setpoint
|
85 °C
|
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
further heating of the reaction mixture
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
at reflux for 3 days
|
|
Duration
|
3 d
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
After cooling
|
EXTRACTION
|
Type
|
EXTRACTION
|
|
Details
|
the crude mixture is extracted by CH2Cl2 (2×250 ml)
|
DRY_WITH_MATERIAL
|
Type
|
DRY_WITH_MATERIAL
|
|
Details
|
The cumulated organic layers are dried over MgSO4
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
filtered
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
condensed under reduced pressure
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The residue is purified over silicagel (eluent: CH2Cl2/MeOH/NH4OH 99/1/0.1)
|
Outcomes
Product
Details
Reaction Time |
1 d |
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
ClC(CC1CC(N(C1)CC1=C(N=C2SC(=NN21)COC)C(F)(F)F)=O)(F)F
|
Measurements
| Type | Value | Analysis |
|---|---|---|
| YIELD: PERCENTYIELD | 74% |
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
US08822508B2
Procedure details
To a hot solution (80° C.) of ZnCl2 (0.23 g, 1.69 mmol, 10 mol %) and 2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazole a28 (4 g, 16.96 mmol) in dioxane (200 ml) is added a solution of 4-(2-chloro-2,2-difluoroethyl)-1-(chloromethyl)pyrrolidin-2-one a18 in dioxane (5 ml). The reaction mixture is heated at 85° C. for 5 days, then a further 2 g of pyrrolidinone a18 is added in one portion and the reaction mixture is kept under agitation at 90° C. for 1 day. A further addition of pyrrolidinone a18 (2 g) in order to insure complete conversion of compound a28 and further heating of the reaction mixture at reflux for 3 days increased significatively the conversion of imidazo[2,1-b][1,3,4]thiadiazole a28. After cooling and hydrolysis (250 ml of water), the crude mixture is extracted by CH2Cl2 (2×250 ml). The cumulated organic layers are dried over MgSO4, filtered and condensed under reduced pressure. The residue is purified over silicagel (eluent: CH2Cl2/MeOH/NH4OH 99/1/0.1) to afford 4-(2-chloro-2,2-difluoroethyl)-1-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}pyrrolidin-2-one 4.
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Four
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Four
Identifiers
|
REACTION_CXSMILES
|
[CH3:1][O:2][CH2:3][C:4]1[S:8][C:7]2=[N:9][C:10]([C:12]([F:15])([F:14])[F:13])=[CH:11][N:6]2[N:5]=1.[Cl:16][C:17]([F:28])([F:27])[CH2:18][CH:19]1[CH2:23][N:22]([CH2:24]Cl)[C:21](=[O:26])[CH2:20]1.N1CCCC1=O.S1C=NN2C=CN=C12>O1CCOCC1.[Cl-].[Cl-].[Zn+2].O>[Cl:16][C:17]([F:27])([F:28])[CH2:18][CH:19]1[CH2:23][N:22]([CH2:24][C:11]2[N:6]3[C:7]([S:8][C:4]([CH2:3][O:2][CH3:1])=[N:5]3)=[N:9][C:10]=2[C:12]([F:15])([F:13])[F:14])[C:21](=[O:26])[CH2:20]1 |f:5.6.7|
|
Inputs
Step One
|
Name
|
|
|
Quantity
|
2 g
|
|
Type
|
reactant
|
|
Smiles
|
N1C(CCC1)=O
|
Step Two
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
N1C(CCC1)=O
|
Step Three
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
S1C=2N(N=C1)C=CN2
|
Step Four
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
COCC1=NN2C(S1)=NC(=C2)C(F)(F)F
|
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
ClC(CC1CC(N(C1)CCl)=O)(F)F
|
|
Name
|
|
|
Quantity
|
200 mL
|
|
Type
|
solvent
|
|
Smiles
|
O1CCOCC1
|
|
Name
|
|
|
Quantity
|
5 mL
|
|
Type
|
solvent
|
|
Smiles
|
O1CCOCC1
|
|
Name
|
|
|
Quantity
|
0.23 g
|
|
Type
|
catalyst
|
|
Smiles
|
[Cl-].[Cl-].[Zn+2]
|
Step Five
|
Name
|
|
|
Quantity
|
250 mL
|
|
Type
|
solvent
|
|
Smiles
|
O
|
Conditions
Temperature
|
Control Type
|
UNSPECIFIED
|
|
Setpoint
|
85 °C
|
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
further heating of the reaction mixture
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
at reflux for 3 days
|
|
Duration
|
3 d
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
After cooling
|
EXTRACTION
|
Type
|
EXTRACTION
|
|
Details
|
the crude mixture is extracted by CH2Cl2 (2×250 ml)
|
DRY_WITH_MATERIAL
|
Type
|
DRY_WITH_MATERIAL
|
|
Details
|
The cumulated organic layers are dried over MgSO4
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
filtered
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
condensed under reduced pressure
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The residue is purified over silicagel (eluent: CH2Cl2/MeOH/NH4OH 99/1/0.1)
|
Outcomes
Product
Details
Reaction Time |
1 d |
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
ClC(CC1CC(N(C1)CC1=C(N=C2SC(=NN21)COC)C(F)(F)F)=O)(F)F
|
Measurements
| Type | Value | Analysis |
|---|---|---|
| YIELD: PERCENTYIELD | 74% |
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. |
