Sitagliptin
Katalognummer B1680988
Molekulargewicht: 407.31 g/mol
InChI-Schlüssel: MFFMDFFZMYYVKS-SECBINFHSA-N
Achtung: Nur für Forschungszwecke. Nicht für den menschlichen oder tierärztlichen Gebrauch.
Patent
US08476437B2
Procedure details
Dibenzoyl-D-tartaric acid salt of 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine was prepared by reacting Dibezoyl-D-tartaric acid monohydrate and 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine in molar equivalent ratio in methanol. The salt was filtered off and filtrate was collected. Solvent was distilled out from the filtrate to obtain enantiomerically enriched desired isomer which was basified in aq. methanol by using NaHCO3. Solvent was again distilled out. The residue was dissolved in ethyl acetate and washed with water and brine solution. Ethyl acetate extract was collected and dried over anhydrous sodium sulfate. Ethyl acetate was distilled out to obtain (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine (% Purity by HPLC-88%, % Chiral purity by HPLC-90.0%).
Name
Dibezoyl-D-tartaric acid monohydrate
Quantity
0 (± 1) mol
Type
reactant
Reaction Step One
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Two
Identifiers
|
REACTION_CXSMILES
|
O.[C:2]([C@:10]([C:25]([OH:27])=[O:26])([OH:24])[C@:11]([C:16](=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)([OH:15])[C:12]([OH:14])=[O:13])(=[O:9])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[O:28]=[C:29]([N:43]1[CH2:48][CH2:47][N:46]2[C:49]([C:52]([F:55])([F:54])[F:53])=[N:50][N:51]=[C:45]2[CH2:44]1)[CH2:30][CH:31]([NH2:42])[CH2:32][C:33]1[CH:38]=[C:37]([F:39])[C:36]([F:40])=[CH:35][C:34]=1[F:41].C([O-])(O)=O.[Na+]>CO>[C:16]([C@:11]([C:12]([OH:14])=[O:13])([OH:15])[C@:10]([C:2](=[O:9])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)([OH:24])[C:25]([OH:27])=[O:26])(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[O:28]=[C:29]([N:43]1[CH2:48][CH2:47][N:46]2[C:49]([C:52]([F:55])([F:54])[F:53])=[N:50][N:51]=[C:45]2[CH2:44]1)[CH2:30][CH:31]([NH2:42])[CH2:32][C:33]1[CH:38]=[C:37]([F:39])[C:36]([F:40])=[CH:35][C:34]=1[F:41].[O:28]=[C:29]([N:43]1[CH2:48][CH2:47][N:46]2[C:49]([C:52]([F:55])([F:54])[F:53])=[N:50][N:51]=[C:45]2[CH2:44]1)[CH2:30][C@H:31]([NH2:42])[CH2:32][C:33]1[CH:38]=[C:37]([F:39])[C:36]([F:40])=[CH:35][C:34]=1[F:41] |f:0.1,3.4|
|
Inputs
Step One
|
Name
|
Dibezoyl-D-tartaric acid monohydrate
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
O.C(C1=CC=CC=C1)(=O)[C@@]([C@@](C(=O)O)(O)C(C1=CC=CC=C1)=O)(O)C(=O)O
|
Step Two
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
O=C(CC(CC1=C(C=C(C(=C1)F)F)F)N)N1CC=2N(CC1)C(=NN2)C(F)(F)F
|
Step Three
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
C(=O)(O)[O-].[Na+]
|
Step Four
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
CO
|
Step Five
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
CO
|
Conditions
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
The salt was filtered off
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
filtrate was collected
|
DISTILLATION
|
Type
|
DISTILLATION
|
|
Details
|
Solvent was distilled out from the filtrate
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
to obtain enantiomerically
|
DISTILLATION
|
Type
|
DISTILLATION
|
|
Details
|
Solvent was again distilled out
|
DISSOLUTION
|
Type
|
DISSOLUTION
|
|
Details
|
The residue was dissolved in ethyl acetate
|
WASH
|
Type
|
WASH
|
|
Details
|
washed with water and brine solution
|
EXTRACTION
|
Type
|
EXTRACTION
|
|
Details
|
Ethyl acetate extract
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
was collected
|
DRY_WITH_MATERIAL
|
Type
|
DRY_WITH_MATERIAL
|
|
Details
|
dried over anhydrous sodium sulfate
|
DISTILLATION
|
Type
|
DISTILLATION
|
|
Details
|
Ethyl acetate was distilled out
|
Outcomes
Product
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
C(C1=CC=CC=C1)(=O)[C@@]([C@@](C(=O)O)(O)C(C1=CC=CC=C1)=O)(O)C(=O)O
|
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
O=C(CC(CC1=C(C=C(C(=C1)F)F)F)N)N1CC=2N(CC1)C(=NN2)C(F)(F)F
|
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
O=C(C[C@@H](CC1=C(C=C(C(=C1)F)F)F)N)N1CC=2N(CC1)C(=NN2)C(F)(F)F
|
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
US08476437B2
Procedure details
Dibenzoyl-D-tartaric acid salt of 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine was prepared by reacting Dibezoyl-D-tartaric acid monohydrate and 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine in molar equivalent ratio in methanol. The salt was filtered off and filtrate was collected. Solvent was distilled out from the filtrate to obtain enantiomerically enriched desired isomer which was basified in aq. methanol by using NaHCO3. Solvent was again distilled out. The residue was dissolved in ethyl acetate and washed with water and brine solution. Ethyl acetate extract was collected and dried over anhydrous sodium sulfate. Ethyl acetate was distilled out to obtain (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine (% Purity by HPLC-88%, % Chiral purity by HPLC-90.0%).
Name
Dibezoyl-D-tartaric acid monohydrate
Quantity
0 (± 1) mol
Type
reactant
Reaction Step One
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Two
Identifiers
|
REACTION_CXSMILES
|
O.[C:2]([C@:10]([C:25]([OH:27])=[O:26])([OH:24])[C@:11]([C:16](=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)([OH:15])[C:12]([OH:14])=[O:13])(=[O:9])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[O:28]=[C:29]([N:43]1[CH2:48][CH2:47][N:46]2[C:49]([C:52]([F:55])([F:54])[F:53])=[N:50][N:51]=[C:45]2[CH2:44]1)[CH2:30][CH:31]([NH2:42])[CH2:32][C:33]1[CH:38]=[C:37]([F:39])[C:36]([F:40])=[CH:35][C:34]=1[F:41].C([O-])(O)=O.[Na+]>CO>[C:16]([C@:11]([C:12]([OH:14])=[O:13])([OH:15])[C@:10]([C:2](=[O:9])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)([OH:24])[C:25]([OH:27])=[O:26])(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[O:28]=[C:29]([N:43]1[CH2:48][CH2:47][N:46]2[C:49]([C:52]([F:55])([F:54])[F:53])=[N:50][N:51]=[C:45]2[CH2:44]1)[CH2:30][CH:31]([NH2:42])[CH2:32][C:33]1[CH:38]=[C:37]([F:39])[C:36]([F:40])=[CH:35][C:34]=1[F:41].[O:28]=[C:29]([N:43]1[CH2:48][CH2:47][N:46]2[C:49]([C:52]([F:55])([F:54])[F:53])=[N:50][N:51]=[C:45]2[CH2:44]1)[CH2:30][C@H:31]([NH2:42])[CH2:32][C:33]1[CH:38]=[C:37]([F:39])[C:36]([F:40])=[CH:35][C:34]=1[F:41] |f:0.1,3.4|
|
Inputs
Step One
|
Name
|
Dibezoyl-D-tartaric acid monohydrate
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
O.C(C1=CC=CC=C1)(=O)[C@@]([C@@](C(=O)O)(O)C(C1=CC=CC=C1)=O)(O)C(=O)O
|
Step Two
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
O=C(CC(CC1=C(C=C(C(=C1)F)F)F)N)N1CC=2N(CC1)C(=NN2)C(F)(F)F
|
Step Three
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
C(=O)(O)[O-].[Na+]
|
Step Four
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
CO
|
Step Five
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
CO
|
Conditions
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
The salt was filtered off
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
filtrate was collected
|
DISTILLATION
|
Type
|
DISTILLATION
|
|
Details
|
Solvent was distilled out from the filtrate
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
to obtain enantiomerically
|
DISTILLATION
|
Type
|
DISTILLATION
|
|
Details
|
Solvent was again distilled out
|
DISSOLUTION
|
Type
|
DISSOLUTION
|
|
Details
|
The residue was dissolved in ethyl acetate
|
WASH
|
Type
|
WASH
|
|
Details
|
washed with water and brine solution
|
EXTRACTION
|
Type
|
EXTRACTION
|
|
Details
|
Ethyl acetate extract
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
was collected
|
DRY_WITH_MATERIAL
|
Type
|
DRY_WITH_MATERIAL
|
|
Details
|
dried over anhydrous sodium sulfate
|
DISTILLATION
|
Type
|
DISTILLATION
|
|
Details
|
Ethyl acetate was distilled out
|
Outcomes
Product
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
C(C1=CC=CC=C1)(=O)[C@@]([C@@](C(=O)O)(O)C(C1=CC=CC=C1)=O)(O)C(=O)O
|
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
O=C(CC(CC1=C(C=C(C(=C1)F)F)F)N)N1CC=2N(CC1)C(=NN2)C(F)(F)F
|
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
O=C(C[C@@H](CC1=C(C=C(C(=C1)F)F)F)N)N1CC=2N(CC1)C(=NN2)C(F)(F)F
|
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
US08476437B2
Procedure details
Dibenzoyl-D-tartaric acid salt of 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine was prepared by reacting Dibezoyl-D-tartaric acid monohydrate and 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine in molar equivalent ratio in methanol. The salt was filtered off and filtrate was collected. Solvent was distilled out from the filtrate to obtain enantiomerically enriched desired isomer which was basified in aq. methanol by using NaHCO3. Solvent was again distilled out. The residue was dissolved in ethyl acetate and washed with water and brine solution. Ethyl acetate extract was collected and dried over anhydrous sodium sulfate. Ethyl acetate was distilled out to obtain (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine (% Purity by HPLC-88%, % Chiral purity by HPLC-90.0%).
Name
Dibezoyl-D-tartaric acid monohydrate
Quantity
0 (± 1) mol
Type
reactant
Reaction Step One
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Two
Identifiers
|
REACTION_CXSMILES
|
O.[C:2]([C@:10]([C:25]([OH:27])=[O:26])([OH:24])[C@:11]([C:16](=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)([OH:15])[C:12]([OH:14])=[O:13])(=[O:9])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[O:28]=[C:29]([N:43]1[CH2:48][CH2:47][N:46]2[C:49]([C:52]([F:55])([F:54])[F:53])=[N:50][N:51]=[C:45]2[CH2:44]1)[CH2:30][CH:31]([NH2:42])[CH2:32][C:33]1[CH:38]=[C:37]([F:39])[C:36]([F:40])=[CH:35][C:34]=1[F:41].C([O-])(O)=O.[Na+]>CO>[C:16]([C@:11]([C:12]([OH:14])=[O:13])([OH:15])[C@:10]([C:2](=[O:9])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)([OH:24])[C:25]([OH:27])=[O:26])(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[O:28]=[C:29]([N:43]1[CH2:48][CH2:47][N:46]2[C:49]([C:52]([F:55])([F:54])[F:53])=[N:50][N:51]=[C:45]2[CH2:44]1)[CH2:30][CH:31]([NH2:42])[CH2:32][C:33]1[CH:38]=[C:37]([F:39])[C:36]([F:40])=[CH:35][C:34]=1[F:41].[O:28]=[C:29]([N:43]1[CH2:48][CH2:47][N:46]2[C:49]([C:52]([F:55])([F:54])[F:53])=[N:50][N:51]=[C:45]2[CH2:44]1)[CH2:30][C@H:31]([NH2:42])[CH2:32][C:33]1[CH:38]=[C:37]([F:39])[C:36]([F:40])=[CH:35][C:34]=1[F:41] |f:0.1,3.4|
|
Inputs
Step One
|
Name
|
Dibezoyl-D-tartaric acid monohydrate
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
O.C(C1=CC=CC=C1)(=O)[C@@]([C@@](C(=O)O)(O)C(C1=CC=CC=C1)=O)(O)C(=O)O
|
Step Two
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
O=C(CC(CC1=C(C=C(C(=C1)F)F)F)N)N1CC=2N(CC1)C(=NN2)C(F)(F)F
|
Step Three
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
C(=O)(O)[O-].[Na+]
|
Step Four
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
CO
|
Step Five
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
CO
|
Conditions
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
The salt was filtered off
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
filtrate was collected
|
DISTILLATION
|
Type
|
DISTILLATION
|
|
Details
|
Solvent was distilled out from the filtrate
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
to obtain enantiomerically
|
DISTILLATION
|
Type
|
DISTILLATION
|
|
Details
|
Solvent was again distilled out
|
DISSOLUTION
|
Type
|
DISSOLUTION
|
|
Details
|
The residue was dissolved in ethyl acetate
|
WASH
|
Type
|
WASH
|
|
Details
|
washed with water and brine solution
|
EXTRACTION
|
Type
|
EXTRACTION
|
|
Details
|
Ethyl acetate extract
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
was collected
|
DRY_WITH_MATERIAL
|
Type
|
DRY_WITH_MATERIAL
|
|
Details
|
dried over anhydrous sodium sulfate
|
DISTILLATION
|
Type
|
DISTILLATION
|
|
Details
|
Ethyl acetate was distilled out
|
Outcomes
Product
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
C(C1=CC=CC=C1)(=O)[C@@]([C@@](C(=O)O)(O)C(C1=CC=CC=C1)=O)(O)C(=O)O
|
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
O=C(CC(CC1=C(C=C(C(=C1)F)F)F)N)N1CC=2N(CC1)C(=NN2)C(F)(F)F
|
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
O=C(C[C@@H](CC1=C(C=C(C(=C1)F)F)F)N)N1CC=2N(CC1)C(=NN2)C(F)(F)F
|
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. |
