Sitagliptin
カタログ番号 B1680988
分子量: 407.31 g/mol
InChIキー: MFFMDFFZMYYVKS-SECBINFHSA-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
US08476437B2
Procedure details
In a 50 mL three neck flask IPA (5 mL) and Dibenzoyl-L-tartaric acid monohydrate (1.84 g) were taken. It was heated to 60-65° C. 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 (2.0 g, % purity-70%) dissolved in methanol (6 mL) was added into reaction mixture at 60-65° C. After 20 min. Dibenzoyl-L-tartaric acid salt of (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 (20 mg, % Chiral purity by HPLC of R-isomer 99.6%) was added as a seeding. It was stirred for 60 min. at 60-65° C. Solid salt was precipitated. It was gradually cooled to room temperature over a period of 2-3 h. The salt was filtered and washed with a mixture of IPA: MeOH (2:1). An enantiomerically enriched desired Dibenzoyl-L-tartaric acid salt of a mixture of (2R) and (2S)-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 obtained (Wt.-0.742 g, % Y-19.2%, Purity by HPLC-99.0%, % Chiral purity by HPLC of R-isomer 78.3%).
[Compound]
Name
three
Quantity
50 mL
Type
reactant
Reaction Step One
Name
Dibenzoyl-L-tartaric acid monohydrate
Quantity
1.84 g
Type
reactant
Reaction Step Two
Quantity
2 g
Type
reactant
Reaction Step Three
Quantity
20 mg
Type
reactant
Reaction Step Four
Identifiers
|
REACTION_CXSMILES
|
O.C([C@@](C(O)=O)(O)[C@@](C(=O)C1C=CC=CC=1)(O)C(O)=O)(=O)C1C=CC=CC=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([C@@](C(O)=O)(O)[C@@](C(=O)C1C=CC=CC=1)(O)C(O)=O)(=O)C1C=CC=CC=1.O=C(N1CCN2C(C(F)(F)F)=NN=C2C1)C[C@H](N)CC1C=C(F)C(F)=CC=1F>CO.CC(O)C>[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|
|
Inputs
Step One
[Compound]
|
Name
|
three
|
|
Quantity
|
50 mL
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Two
|
Name
|
Dibenzoyl-L-tartaric acid monohydrate
|
|
Quantity
|
1.84 g
|
|
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 Three
|
Name
|
|
|
Quantity
|
2 g
|
|
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
|
|
Name
|
|
|
Quantity
|
6 mL
|
|
Type
|
solvent
|
|
Smiles
|
CO
|
Step Four
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
C(C1=CC=CC=C1)(=O)[C@]([C@](C(=O)O)(O)C(C1=CC=CC=C1)=O)(O)C(=O)O
|
|
Name
|
|
|
Quantity
|
20 mg
|
|
Type
|
reactant
|
|
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
|
Step Five
|
Name
|
|
|
Quantity
|
5 mL
|
|
Type
|
solvent
|
|
Smiles
|
CC(C)O
|
Conditions
Temperature
|
Control Type
|
UNSPECIFIED
|
|
Setpoint
|
62.5 (± 2.5) °C
|
Stirring
|
Type
|
CUSTOM
|
|
Details
|
It was stirred for 60 min. at 60-65° C
|
|
Rate
|
UNSPECIFIED
|
|
RPM
|
0
|
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
ADDITION
|
Type
|
ADDITION
|
|
Details
|
was added into reaction mixture at 60-65° C
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
Solid salt was precipitated
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
It was gradually cooled to room temperature over a period of 2-3 h
|
|
Duration
|
2.5 (± 0.5) h
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
The salt was filtered
|
WASH
|
Type
|
WASH
|
|
Details
|
washed with a mixture of IPA: MeOH (2:1)
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
An enantiomerically enriched desired Dibenzoyl-L-tartaric acid salt of a mixture of (2R)
|
Outcomes
Product
Details
Reaction Time |
20 min |
|
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
In a 50 mL three neck flask IPA (5 mL) and Dibenzoyl-L-tartaric acid monohydrate (1.84 g) were taken. It was heated to 60-65° C. 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 (2.0 g, % purity-70%) dissolved in methanol (6 mL) was added into reaction mixture at 60-65° C. After 20 min. Dibenzoyl-L-tartaric acid salt of (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 (20 mg, % Chiral purity by HPLC of R-isomer 99.6%) was added as a seeding. It was stirred for 60 min. at 60-65° C. Solid salt was precipitated. It was gradually cooled to room temperature over a period of 2-3 h. The salt was filtered and washed with a mixture of IPA: MeOH (2:1). An enantiomerically enriched desired Dibenzoyl-L-tartaric acid salt of a mixture of (2R) and (2S)-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 obtained (Wt.-0.742 g, % Y-19.2%, Purity by HPLC-99.0%, % Chiral purity by HPLC of R-isomer 78.3%).
[Compound]
Name
three
Quantity
50 mL
Type
reactant
Reaction Step One
Name
Dibenzoyl-L-tartaric acid monohydrate
Quantity
1.84 g
Type
reactant
Reaction Step Two
Quantity
2 g
Type
reactant
Reaction Step Three
Quantity
20 mg
Type
reactant
Reaction Step Four
Identifiers
|
REACTION_CXSMILES
|
O.C([C@@](C(O)=O)(O)[C@@](C(=O)C1C=CC=CC=1)(O)C(O)=O)(=O)C1C=CC=CC=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([C@@](C(O)=O)(O)[C@@](C(=O)C1C=CC=CC=1)(O)C(O)=O)(=O)C1C=CC=CC=1.O=C(N1CCN2C(C(F)(F)F)=NN=C2C1)C[C@H](N)CC1C=C(F)C(F)=CC=1F>CO.CC(O)C>[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|
|
Inputs
Step One
[Compound]
|
Name
|
three
|
|
Quantity
|
50 mL
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Two
|
Name
|
Dibenzoyl-L-tartaric acid monohydrate
|
|
Quantity
|
1.84 g
|
|
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 Three
|
Name
|
|
|
Quantity
|
2 g
|
|
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
|
|
Name
|
|
|
Quantity
|
6 mL
|
|
Type
|
solvent
|
|
Smiles
|
CO
|
Step Four
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
C(C1=CC=CC=C1)(=O)[C@]([C@](C(=O)O)(O)C(C1=CC=CC=C1)=O)(O)C(=O)O
|
|
Name
|
|
|
Quantity
|
20 mg
|
|
Type
|
reactant
|
|
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
|
Step Five
|
Name
|
|
|
Quantity
|
5 mL
|
|
Type
|
solvent
|
|
Smiles
|
CC(C)O
|
Conditions
Temperature
|
Control Type
|
UNSPECIFIED
|
|
Setpoint
|
62.5 (± 2.5) °C
|
Stirring
|
Type
|
CUSTOM
|
|
Details
|
It was stirred for 60 min. at 60-65° C
|
|
Rate
|
UNSPECIFIED
|
|
RPM
|
0
|
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
ADDITION
|
Type
|
ADDITION
|
|
Details
|
was added into reaction mixture at 60-65° C
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
Solid salt was precipitated
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
It was gradually cooled to room temperature over a period of 2-3 h
|
|
Duration
|
2.5 (± 0.5) h
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
The salt was filtered
|
WASH
|
Type
|
WASH
|
|
Details
|
washed with a mixture of IPA: MeOH (2:1)
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
An enantiomerically enriched desired Dibenzoyl-L-tartaric acid salt of a mixture of (2R)
|
Outcomes
Product
Details
Reaction Time |
20 min |
|
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
In a 50 mL three neck flask IPA (5 mL) and Dibenzoyl-L-tartaric acid monohydrate (1.84 g) were taken. It was heated to 60-65° C. 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 (2.0 g, % purity-70%) dissolved in methanol (6 mL) was added into reaction mixture at 60-65° C. After 20 min. Dibenzoyl-L-tartaric acid salt of (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 (20 mg, % Chiral purity by HPLC of R-isomer 99.6%) was added as a seeding. It was stirred for 60 min. at 60-65° C. Solid salt was precipitated. It was gradually cooled to room temperature over a period of 2-3 h. The salt was filtered and washed with a mixture of IPA: MeOH (2:1). An enantiomerically enriched desired Dibenzoyl-L-tartaric acid salt of a mixture of (2R) and (2S)-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 obtained (Wt.-0.742 g, % Y-19.2%, Purity by HPLC-99.0%, % Chiral purity by HPLC of R-isomer 78.3%).
[Compound]
Name
three
Quantity
50 mL
Type
reactant
Reaction Step One
Name
Dibenzoyl-L-tartaric acid monohydrate
Quantity
1.84 g
Type
reactant
Reaction Step Two
Quantity
2 g
Type
reactant
Reaction Step Three
Quantity
20 mg
Type
reactant
Reaction Step Four
Identifiers
|
REACTION_CXSMILES
|
O.C([C@@](C(O)=O)(O)[C@@](C(=O)C1C=CC=CC=1)(O)C(O)=O)(=O)C1C=CC=CC=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([C@@](C(O)=O)(O)[C@@](C(=O)C1C=CC=CC=1)(O)C(O)=O)(=O)C1C=CC=CC=1.O=C(N1CCN2C(C(F)(F)F)=NN=C2C1)C[C@H](N)CC1C=C(F)C(F)=CC=1F>CO.CC(O)C>[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|
|
Inputs
Step One
[Compound]
|
Name
|
three
|
|
Quantity
|
50 mL
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Two
|
Name
|
Dibenzoyl-L-tartaric acid monohydrate
|
|
Quantity
|
1.84 g
|
|
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 Three
|
Name
|
|
|
Quantity
|
2 g
|
|
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
|
|
Name
|
|
|
Quantity
|
6 mL
|
|
Type
|
solvent
|
|
Smiles
|
CO
|
Step Four
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
C(C1=CC=CC=C1)(=O)[C@]([C@](C(=O)O)(O)C(C1=CC=CC=C1)=O)(O)C(=O)O
|
|
Name
|
|
|
Quantity
|
20 mg
|
|
Type
|
reactant
|
|
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
|
Step Five
|
Name
|
|
|
Quantity
|
5 mL
|
|
Type
|
solvent
|
|
Smiles
|
CC(C)O
|
Conditions
Temperature
|
Control Type
|
UNSPECIFIED
|
|
Setpoint
|
62.5 (± 2.5) °C
|
Stirring
|
Type
|
CUSTOM
|
|
Details
|
It was stirred for 60 min. at 60-65° C
|
|
Rate
|
UNSPECIFIED
|
|
RPM
|
0
|
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
ADDITION
|
Type
|
ADDITION
|
|
Details
|
was added into reaction mixture at 60-65° C
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
Solid salt was precipitated
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
It was gradually cooled to room temperature over a period of 2-3 h
|
|
Duration
|
2.5 (± 0.5) h
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
The salt was filtered
|
WASH
|
Type
|
WASH
|
|
Details
|
washed with a mixture of IPA: MeOH (2:1)
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
An enantiomerically enriched desired Dibenzoyl-L-tartaric acid salt of a mixture of (2R)
|
Outcomes
Product
Details
Reaction Time |
20 min |
|
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. |
