Imatinib
Numéro de catalogue B000729
Poids moléculaire: 493.6 g/mol
Clé InChI: KTUFNOKKBVMGRW-UHFFFAOYSA-N
Attention: Uniquement pour un usage de recherche. Non destiné à un usage humain ou vétérinaire.
Patent
US07456283B2
Procedure details
To a mixture of 4-(3-pyridyl)-2-pyrimidine-amine (172.2 mg, 1.0 mmol), N-(3-bromo-4-methyl-phenyl)-4-(4-methyl-piperazin-1-ylmethyl)-benzamide (402.4 mg, 1.0 mmol) and sodium tert.-butylate (144.2 mg, 1.5 mmol) is added a mixture of rac-BINAP (31.2 mg, 0.050 mmol) and Pd2(dba)3*CHCl3 (13 mg, 0.013 mmol) under argon. After addition of 3 ml of xylene the suspension is sonicated for 10 minutes then stirred for 5 hours under reflux. After cooling to room temperature, water (10 ml) is added to the dark brown oil and the product extracted 4 times with methylene chloride (10 ml each). The combined organic extracts are dried over MgSO4 and concentrated in vacuo. The brown oil is purified by flash-chromatography (SiO2, methanol). The product, a pale yellow solid is dissolved in methylene chloride, filtered and concentrated in vacuo. Yield: 484.3 mg of the title compound, 72% of theory, (99.9% area by HPLC). The product contains typically roughly 10% of isomers which can be eliminated by preparative reversed phase chromatography.
Name
N-(3-bromo-4-methyl-phenyl)-4-(4-methyl-piperazin-1-ylmethyl)-benzamide
Quantity
402.4 mg
Type
reactant
Reaction Step One
[Compound]
Name
sodium tert.-butylate
Quantity
144.2 mg
Type
reactant
Reaction Step One
Identifiers
|
REACTION_CXSMILES
|
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH2:13])[N:8]=2)[CH:2]=1.Br[C:15]1[CH:16]=[C:17]([NH:22][C:23](=[O:38])[C:24]2[CH:29]=[CH:28][C:27]([CH2:30][N:31]3[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]3)=[CH:26][CH:25]=2)[CH:18]=[CH:19][C:20]=1[CH3:21].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C(C)=CC=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH3:37][N:34]1[CH2:33][CH2:32][N:31]([CH2:30][C:27]2[CH:28]=[CH:29][C:24]([C:23]([NH:22][C:17]3[CH:16]=[CH:15][C:20]([CH3:21])=[C:19]([NH:13][C:9]4[N:8]=[C:7]([C:3]5[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=5)[CH:12]=[CH:11][N:10]=4)[CH:18]=3)=[O:38])=[CH:25][CH:26]=2)[CH2:36][CH2:35]1 |f:4.5.6.7.8|
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Inputs
Step One
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Name
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|
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Quantity
|
172.2 mg
|
|
Type
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reactant
|
|
Smiles
|
N1=CC(=CC=C1)C1=NC(=NC=C1)N
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|
Name
|
N-(3-bromo-4-methyl-phenyl)-4-(4-methyl-piperazin-1-ylmethyl)-benzamide
|
|
Quantity
|
402.4 mg
|
|
Type
|
reactant
|
|
Smiles
|
BrC=1C=C(C=CC1C)NC(C1=CC=C(C=C1)CN1CCN(CC1)C)=O
|
[Compound]
|
Name
|
sodium tert.-butylate
|
|
Quantity
|
144.2 mg
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Two
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Name
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|
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Quantity
|
31.2 mg
|
|
Type
|
reactant
|
|
Smiles
|
C=1C=CC(=CC1)P(C=2C=CC=CC2)C3=CC=C4C=CC=CC4=C3C5=C6C=CC=CC6=CC=C5P(C=7C=CC=CC7)C=8C=CC=CC8
|
|
Name
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Quantity
|
13 mg
|
|
Type
|
catalyst
|
|
Smiles
|
C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd]
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Step Three
|
Name
|
|
|
Quantity
|
3 mL
|
|
Type
|
reactant
|
|
Smiles
|
C=1(C(=CC=CC1)C)C
|
Step Four
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Name
|
|
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Quantity
|
10 mL
|
|
Type
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solvent
|
|
Smiles
|
O
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Conditions
Temperature
|
Control Type
|
AMBIENT
|
Stirring
|
Type
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CUSTOM
|
|
Details
|
then stirred for 5 hours
|
|
Rate
|
UNSPECIFIED
|
|
RPM
|
0
|
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
ADDITION
|
Type
|
ADDITION
|
|
Details
|
is added
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CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
is sonicated for 10 minutes
|
|
Duration
|
10 min
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TEMPERATURE
|
Type
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TEMPERATURE
|
|
Details
|
under reflux
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EXTRACTION
|
Type
|
EXTRACTION
|
|
Details
|
the product extracted 4 times with methylene chloride (10 ml each)
|
DRY_WITH_MATERIAL
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Type
|
DRY_WITH_MATERIAL
|
|
Details
|
The combined organic extracts are dried over MgSO4
|
CONCENTRATION
|
Type
|
CONCENTRATION
|
|
Details
|
concentrated in vacuo
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The brown oil is purified by flash-chromatography (SiO2, methanol)
|
DISSOLUTION
|
Type
|
DISSOLUTION
|
|
Details
|
The product, a pale yellow solid is dissolved in methylene chloride
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
filtered
|
CONCENTRATION
|
Type
|
CONCENTRATION
|
|
Details
|
concentrated in vacuo
|
Outcomes
Product
Details
Reaction Time |
5 h |
|
Name
|
|
|
Type
|
|
|
Smiles
|
CN1CCN(CC1)CC1=CC=C(C(=O)NC2=CC(=C(C=C2)C)NC2=NC=CC(=N2)C=2C=NC=CC2)C=C1
|
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. |
