Sitagliptin
货号 B1680988
分子量: 407.31 g/mol
InChI 键: MFFMDFFZMYYVKS-SECBINFHSA-N
注意: 仅供研究使用。不适用于人类或兽医用途。
Patent
US08476437B2
Procedure details
In a 50 mL three neck flask IPA (5 mL), water (2 mL) and Dibenzoyl-L-tartaric acid monohydrate (1.84 g) were taken. It was heated to 40-45° 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-94%) dissolved in IPA (5 mL) was added into reaction mixture at 60-65° C. It was stirred for 1 h at 60-65° C. It was gradually cooled to room temperature. Then it was further cooled to 0-5° C. and stirred for 1 h. The salt was filtered and washed with cold IPA. An enantiomerically enriched desired Dibenzoyl-L-tartaric acid salt of 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.-1.1 g, % Y-28.7%, Purity by HPLC-99.1%, % Chiral purity by HPLC of R-isomer 74%).
[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 Three
Quantity
2 g
Type
reactant
Reaction Step Four
Identifiers
|
REACTION_CXSMILES
|
O.O.C([C@@](C(O)=O)(O)[C@@](C(=O)C1C=CC=CC=1)(O)C(O)=O)(=O)C1C=CC=CC=1.[O:29]=[C:30]([N:44]1[CH2:49][CH2:48][N:47]2[C:50]([C:53]([F:56])([F:55])[F:54])=[N:51][N:52]=[C:46]2[CH2:45]1)[CH2:31][CH:32]([NH2:43])[CH2:33][C:34]1[CH:39]=[C:38]([F:40])[C:37]([F:41])=[CH:36][C:35]=1[F:42]>CC(O)C>[O:29]=[C:30]([N:44]1[CH2:49][CH2:48][N:47]2[C:50]([C:53]([F:56])([F:55])[F:54])=[N:51][N:52]=[C:46]2[CH2:45]1)[CH2:31][C@@H:32]([NH2:43])[CH2:33][C:34]1[CH:39]=[C:38]([F:40])[C:37]([F:41])=[CH:36][C:35]=1[F:42] |f:1.2|
|
Inputs
Step One
[Compound]
|
Name
|
three
|
|
Quantity
|
50 mL
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Two
|
Name
|
|
|
Quantity
|
2 mL
|
|
Type
|
reactant
|
|
Smiles
|
O
|
Step Three
|
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 Four
|
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
|
5 mL
|
|
Type
|
solvent
|
|
Smiles
|
CC(C)O
|
Step Five
|
Name
|
|
|
Quantity
|
5 mL
|
|
Type
|
solvent
|
|
Smiles
|
CC(C)O
|
Conditions
Temperature
|
Control Type
|
UNSPECIFIED
|
|
Setpoint
|
42.5 (± 2.5) °C
|
Stirring
|
Type
|
CUSTOM
|
|
Details
|
It was stirred for 1 h 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
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
It was gradually cooled to room temperature
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
Then it was further cooled to 0-5° C.
|
STIRRING
|
Type
|
STIRRING
|
|
Details
|
stirred for 1 h
|
|
Duration
|
1 h
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
The salt was filtered
|
WASH
|
Type
|
WASH
|
|
Details
|
washed with cold IPA
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
An enantiomerically enriched desired Dibenzoyl-L-tartaric acid salt of mixture of (2R)
|
Outcomes
Product
Details
Reaction Time |
1 h |
|
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), water (2 mL) and Dibenzoyl-L-tartaric acid monohydrate (1.84 g) were taken. It was heated to 40-45° 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-94%) dissolved in IPA (5 mL) was added into reaction mixture at 60-65° C. It was stirred for 1 h at 60-65° C. It was gradually cooled to room temperature. Then it was further cooled to 0-5° C. and stirred for 1 h. The salt was filtered and washed with cold IPA. An enantiomerically enriched desired Dibenzoyl-L-tartaric acid salt of 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.-1.1 g, % Y-28.7%, Purity by HPLC-99.1%, % Chiral purity by HPLC of R-isomer 74%).
[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 Three
Quantity
2 g
Type
reactant
Reaction Step Four
Identifiers
|
REACTION_CXSMILES
|
O.O.C([C@@](C(O)=O)(O)[C@@](C(=O)C1C=CC=CC=1)(O)C(O)=O)(=O)C1C=CC=CC=1.[O:29]=[C:30]([N:44]1[CH2:49][CH2:48][N:47]2[C:50]([C:53]([F:56])([F:55])[F:54])=[N:51][N:52]=[C:46]2[CH2:45]1)[CH2:31][CH:32]([NH2:43])[CH2:33][C:34]1[CH:39]=[C:38]([F:40])[C:37]([F:41])=[CH:36][C:35]=1[F:42]>CC(O)C>[O:29]=[C:30]([N:44]1[CH2:49][CH2:48][N:47]2[C:50]([C:53]([F:56])([F:55])[F:54])=[N:51][N:52]=[C:46]2[CH2:45]1)[CH2:31][C@@H:32]([NH2:43])[CH2:33][C:34]1[CH:39]=[C:38]([F:40])[C:37]([F:41])=[CH:36][C:35]=1[F:42] |f:1.2|
|
Inputs
Step One
[Compound]
|
Name
|
three
|
|
Quantity
|
50 mL
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Two
|
Name
|
|
|
Quantity
|
2 mL
|
|
Type
|
reactant
|
|
Smiles
|
O
|
Step Three
|
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 Four
|
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
|
5 mL
|
|
Type
|
solvent
|
|
Smiles
|
CC(C)O
|
Step Five
|
Name
|
|
|
Quantity
|
5 mL
|
|
Type
|
solvent
|
|
Smiles
|
CC(C)O
|
Conditions
Temperature
|
Control Type
|
UNSPECIFIED
|
|
Setpoint
|
42.5 (± 2.5) °C
|
Stirring
|
Type
|
CUSTOM
|
|
Details
|
It was stirred for 1 h 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
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
It was gradually cooled to room temperature
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
Then it was further cooled to 0-5° C.
|
STIRRING
|
Type
|
STIRRING
|
|
Details
|
stirred for 1 h
|
|
Duration
|
1 h
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
The salt was filtered
|
WASH
|
Type
|
WASH
|
|
Details
|
washed with cold IPA
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
An enantiomerically enriched desired Dibenzoyl-L-tartaric acid salt of mixture of (2R)
|
Outcomes
Product
Details
Reaction Time |
1 h |
|
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), water (2 mL) and Dibenzoyl-L-tartaric acid monohydrate (1.84 g) were taken. It was heated to 40-45° 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-94%) dissolved in IPA (5 mL) was added into reaction mixture at 60-65° C. It was stirred for 1 h at 60-65° C. It was gradually cooled to room temperature. Then it was further cooled to 0-5° C. and stirred for 1 h. The salt was filtered and washed with cold IPA. An enantiomerically enriched desired Dibenzoyl-L-tartaric acid salt of 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.-1.1 g, % Y-28.7%, Purity by HPLC-99.1%, % Chiral purity by HPLC of R-isomer 74%).
[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 Three
Quantity
2 g
Type
reactant
Reaction Step Four
Identifiers
|
REACTION_CXSMILES
|
O.O.C([C@@](C(O)=O)(O)[C@@](C(=O)C1C=CC=CC=1)(O)C(O)=O)(=O)C1C=CC=CC=1.[O:29]=[C:30]([N:44]1[CH2:49][CH2:48][N:47]2[C:50]([C:53]([F:56])([F:55])[F:54])=[N:51][N:52]=[C:46]2[CH2:45]1)[CH2:31][CH:32]([NH2:43])[CH2:33][C:34]1[CH:39]=[C:38]([F:40])[C:37]([F:41])=[CH:36][C:35]=1[F:42]>CC(O)C>[O:29]=[C:30]([N:44]1[CH2:49][CH2:48][N:47]2[C:50]([C:53]([F:56])([F:55])[F:54])=[N:51][N:52]=[C:46]2[CH2:45]1)[CH2:31][C@@H:32]([NH2:43])[CH2:33][C:34]1[CH:39]=[C:38]([F:40])[C:37]([F:41])=[CH:36][C:35]=1[F:42] |f:1.2|
|
Inputs
Step One
[Compound]
|
Name
|
three
|
|
Quantity
|
50 mL
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Two
|
Name
|
|
|
Quantity
|
2 mL
|
|
Type
|
reactant
|
|
Smiles
|
O
|
Step Three
|
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 Four
|
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
|
5 mL
|
|
Type
|
solvent
|
|
Smiles
|
CC(C)O
|
Step Five
|
Name
|
|
|
Quantity
|
5 mL
|
|
Type
|
solvent
|
|
Smiles
|
CC(C)O
|
Conditions
Temperature
|
Control Type
|
UNSPECIFIED
|
|
Setpoint
|
42.5 (± 2.5) °C
|
Stirring
|
Type
|
CUSTOM
|
|
Details
|
It was stirred for 1 h 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
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
It was gradually cooled to room temperature
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
Then it was further cooled to 0-5° C.
|
STIRRING
|
Type
|
STIRRING
|
|
Details
|
stirred for 1 h
|
|
Duration
|
1 h
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
The salt was filtered
|
WASH
|
Type
|
WASH
|
|
Details
|
washed with cold IPA
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
An enantiomerically enriched desired Dibenzoyl-L-tartaric acid salt of mixture of (2R)
|
Outcomes
Product
Details
Reaction Time |
1 h |
|
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. |
