Nilotinib
货号 B1678881
分子量: 529.5 g/mol
InChI 键: HHZIURLSWUIHRB-UHFFFAOYSA-N
注意: 仅供研究使用。不适用于人类或兽医用途。
Patent
US08937082B2
Procedure details
To a 1 liter reactor was fed 40 g of 4-methyl-3-(4-(pyridine-3-yl)pyrimidin-2-ylamino)benzoic acid (0.13 mol), 200 ml of N-methylpyrrolidone (NMP) (5V) and 13 ml of thionyl chloride (0.18 mol). The reactor was heated to 60° C. and maintained at 60° C. for 1.5 hr. After 1.5 hr of heating, 31.5 g of 3-(trifluoromethyl)-5-(4-methyl-1H-imidazol-1-yl)benzenamine (0.13 mol) was fed into the reactor. The reactor was then heated to 90° C., and maintained for 30 minutes at this temperature. Then 200 ml (5V) of water was added. The resulting mixture was maintained for 2 hours at 90° C. Then, an additional 240 ml (6V) of N-methylpyrrolidone was added, followed by 26.5 ml of sodium hydroxide (47% aqueous) to raise the pH to 6.5-7. The reactor was then cooled to 40° C. and maintained for 3 hours. The mixture was then filtered and the filter cake was washed with ethanol and water. The washed material was then dried in a vacuum tray oven overnight to provide dry Nilotinib base (62.1 g, Yield 90%)
Quantity
40 g
Type
reactant
Reaction Step One
Quantity
31.5 g
Type
reactant
Reaction Step Three
Identifiers
|
REACTION_CXSMILES
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[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[NH:11][C:12]1[N:17]=[C:16]([C:18]2[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=2)[CH:15]=[CH:14][N:13]=1.S(Cl)(Cl)=O.[F:28][C:29]([F:44])([F:43])[C:30]1[CH:31]=[C:32]([NH2:42])[CH:33]=[C:34]([N:36]2[CH:40]=[C:39]([CH3:41])[N:38]=[CH:37]2)[CH:35]=1.[OH-].[Na+]>CN1CCCC1=O>[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:42][C:32]2[CH:31]=[C:30]([C:29]([F:44])([F:43])[F:28])[CH:35]=[C:34]([N:36]3[CH:37]=[N:38][C:39]([CH3:41])=[CH:40]3)[CH:33]=2)=[O:8])=[CH:4][C:3]=1[NH:11][C:12]1[N:13]=[CH:14][CH:15]=[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[N:20][CH:19]=2)[N:17]=1 |f:3.4|
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Inputs
Step One
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Name
|
|
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Quantity
|
40 g
|
|
Type
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reactant
|
|
Smiles
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CC1=C(C=C(C(=O)O)C=C1)NC1=NC=CC(=N1)C=1C=NC=CC1
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Step Two
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Name
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|
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Quantity
|
13 mL
|
|
Type
|
reactant
|
|
Smiles
|
S(=O)(Cl)Cl
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Step Three
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Name
|
|
|
Quantity
|
31.5 g
|
|
Type
|
reactant
|
|
Smiles
|
FC(C=1C=C(C=C(C1)N1C=NC(=C1)C)N)(F)F
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Step Four
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Name
|
|
|
Quantity
|
26.5 mL
|
|
Type
|
reactant
|
|
Smiles
|
[OH-].[Na+]
|
Step Five
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Name
|
|
|
Quantity
|
240 mL
|
|
Type
|
solvent
|
|
Smiles
|
CN1C(CCC1)=O
|
Step Six
|
Name
|
|
|
Quantity
|
200 mL
|
|
Type
|
solvent
|
|
Smiles
|
CN1C(CCC1)=O
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Step Seven
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Name
|
|
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Quantity
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200 mL
|
|
Type
|
solvent
|
|
Smiles
|
CN1C(CCC1)=O
|
Conditions
Temperature
|
Control Type
|
UNSPECIFIED
|
|
Setpoint
|
60 °C
|
Other
|
Conditions are dynamic
|
1
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Details
|
See reaction.notes.procedure_details.
|
Workups
CUSTOM
|
Type
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CUSTOM
|
|
Details
|
To a 1 liter reactor was fed
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
maintained at 60° C. for 1.5 hr
|
|
Duration
|
1.5 h
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
After 1.5 hr of heating
|
|
Duration
|
1.5 h
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
The reactor was then heated to 90° C.
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
maintained for 30 minutes at this temperature
|
|
Duration
|
30 min
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
The resulting mixture was maintained for 2 hours at 90° C
|
|
Duration
|
2 h
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
to raise the pH to 6.5-7
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
The reactor was then cooled to 40° C.
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
maintained for 3 hours
|
|
Duration
|
3 h
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
The mixture was then filtered
|
WASH
|
Type
|
WASH
|
|
Details
|
the filter cake was washed with ethanol and water
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CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The washed material was then dried in a vacuum tray oven overnight
|
|
Duration
|
8 (± 8) h
|
Outcomes
Product
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
CC=1C=CC(=CC1NC=2N=CC=C(N2)C=3C=CC=NC3)C(=O)NC=4C=C(C=C(C4)N5C=C(N=C5)C)C(F)(F)F
|
Measurements
| Type | Value | Analysis |
|---|---|---|
| AMOUNT: MASS | 62.1 g | |
| YIELD: PERCENTYIELD | 90% | |
| YIELD: CALCULATEDPERCENTYIELD | 90.2% |
Source
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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. |
