283173-50-2 Usage
Description
8-FLUOR-2-4-[(METHYLAMINO)METHYL]FENYL-1,3,4,5-TETRAHYDRO-6HAZEPINO[5,4,3-CD]INDOOL-6-ON is a complex organic compound with a molecular structure that features a fluorine atom at the 8th position, a methylamino group attached to a phenyl ring, and a tetrahydroazepinoindol core. 8-FLUOR-2-4-[(METHYLAMINO)METHYL]FENYL-1,3,4,5-TETRAHYDRO-6HAZEPINO[5,4,3-CD]INDOOL-6-ON is characterized by its unique chemical properties and potential applications in various fields.
Uses
1. Used in Pharmaceutical Industry:
8-FLUOR-2-4-[(METHYLAMINO)METHYL]FENYL-1,3,4,5-TETRAHYDRO-6HAZEPINO[5,4,3-CD]INDOOL-6-ON is used as a pharmaceutical compound for its potential therapeutic effects. 8-FLUOR-2-4-[(METHYLAMINO)METHYL]FENYL-1,3,4,5-TETRAHYDRO-6HAZEPINO[5,4,3-CD]INDOOL-6-ON's unique structure may allow it to interact with specific biological targets, making it a candidate for the development of new drugs.
2. Used in Chemical Research:
8-FLUOR-2-4-[(METHYLAMINO)METHYL]FENYL-1,3,4,5-TETRAHYDRO-6HAZEPINO[5,4,3-CD]INDOOL-6-ON is used as a research tool in chemical screening to identify drugs that enhance or mitigate cellular responses to various stimuli. Its unique chemical properties make it a valuable compound for studying the mechanisms of cellular responses and developing targeted therapies.
3. Used in Material Science:
8-FLUOR-2-4-[(METHYLAMINO)METHYL]FENYL-1,3,4,5-TETRAHYDRO-6HAZEPINO[5,4,3-CD]INDOOL-6-ON may also find applications in material science due to its potential to form novel materials with specific properties. 8-FLUOR-2-4-[(METHYLAMINO)METHYL]FENYL-1,3,4,5-TETRAHYDRO-6HAZEPINO[5,4,3-CD]INDOOL-6-ON's structure could be exploited to create new materials with applications in various industries, such as electronics, coatings, or adhesives.
Mechanism of action
Rucaparib inhibits "the contraction of isolated vascular smooth muscle, including that from the tumours of cancer patients. It also reduces the migration of some cancer and normal cells in culture." As a PARP inhibitor, rucaparib is expected to be more effective in the 9% of pancreatic cancers with a BRCA mutation (BRCA1 or BRCA2).
Synthesis
Synthesis of rucaparib camsylate begins from commercially
available phthalimide acetal 151. Unveiling of
the aldehyde via treatment with aqueous HCl and precipitation
from toluene provided aldehyde 152 in 62% yield. To avoid
polymerization, 152 was immediately subjected to 6-fluoro-1Hindole-
4-carboxylic acid methyl ester (153) under reductive
conditions in the presence of acid to give rise to tryptamine
derivative 154. After considerable research, optimal conditions
for this transformation (triethylsilane in DCM/TFA) were
found that were successful on up to 15.7 kg scale, enabling
clean separation of the aldehyde reduction byproduct following
crystallization. Conversion of the phthalimide within 154 to
the corresponding amine using aqueous methylamine at room
temperature was accompanied by an intramolecular cyclization
reaction to secure the intermediate lactam as a solid in 89%
isolated yield. This was followed by a high-yielding bromination
reaction (83%) at the indole C-2 position employing
pyridinium tribromide, providing access to indoloazepinone
155. After screening various catalysts for the coupling of
bromide 155 and commercial boronic acid 156, Pd(dppf)Cl2·
DCM was found to reliably deliver the desired coupling
product with reasonable rates of reaction. Thus, after
development of an extensively optimized reaction protocol,
Suzuki coupling of 155 and 4-formylphenylboronic acid (156)
with Pd(dppf)Cl2·DCM and Na2CO3 in DMA at 90 °C
generated the desired 2-arylated indole 157 in high yield (92%)
after trituration and reslurry with methanol. Conversion of
aldehyde 157 to amine 158 necessitated a two-pot procedure
designed to limit the formation of dimerization and aldehyde
reduction products that generally arise under conventional onepot
reductive amination conditions and have traditionally been
problematic on scale. Toward this end, subjection of aldehyde
157 to a methylamine solution in EtOH/MeOH/THF and
wash of the resulting reaction solids with methanol led to
efficient isolation of pure imine intermediate, which could be
immediately reduced with NaBH4 in THF/MeOH, providing
hydrochloride salt 158 upon acidic workup in 76% over two steps. The two remaining steps for conversion to the drug
involve a salt-swap, first breaking the HCl salt with NaOH in
MeOH, then treatment with (S)-camphorsulfonic acid/IPA/
H2O at 70 °C. Filtration and washing of the cake with water
generated rucaparib camsylate (XVII) in 95% yield.
Check Digit Verification of cas no
The CAS Registry Mumber 283173-50-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,8,3,1,7 and 3 respectively; the second part has 2 digits, 5 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 283173-50:
(8*2)+(7*8)+(6*3)+(5*1)+(4*7)+(3*3)+(2*5)+(1*0)=142
142 % 10 = 2
So 283173-50-2 is a valid CAS Registry Number.
283173-50-2Relevant articles and documents
Late-Stage C-H Arylation of Azepinoindole via Pd/Cu Catalysis: A Step Efficient and Convergent Synthesis of Rucaparib
Beckers, Igor,De Vos, Dirk,O'Rourke, Galahad
, (2021/10/01)
The C-H arylation of indoles holds the promise to shorten synthetic routes in the production of pharmaceuticals. However, latestage C-H activation reactions often rely on the presence of protecting groups or stoichiometric metal additives. The regiospecific C-H arylation of a highly functionalized azepino[5,3,4-cd]indole scaffold lacking directing groups via Pd(II) and Cu(II) co-catalysis is reported. The direct C-H coupling was demonstrated in the convergent synthesis of rucaparib, an FDA approved anticancer drug.
Preparation method of 3, 4-bridged ring indole compound and synthetic method of Rucaparib
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Paragraph 0045; 0050, (2020/09/20)
The invention relates to a preparation method of a 3, 4-bridged ring indole compound. The method comprises the following steps of: adding an o-alkyne iodobenzene derivative (1), diazacycloacetone (2),a palladium salt, a ligand, an inorganic base and an organic solvent into a reaction tube, replacing the system with inert gas, carrying out heating reaction, and then performing separating and purifying to obtain the 3, 4-bridged ring indole compound (3). The invention further provides a preparation method of a Rucaparib drug molecule capable of being used for treating ovarian cancer. The methodis efficient and simple, the traditional method of synthesizing a target product by using functionalized indole is avoided, and the method has high atomic economic effect, is greener and more environmentally friendly, the synthetic method has the characteristics of cheap and easily available raw materials, mild reaction conditions, simple operation, stable product quality, high purity and the like, and has great application value in the synthesis of physiologically active natural products and drug molecules containing 3, 4-bridged ring indole skeleton.
CRYSTALLINE OF CAMPHORSULFONIC ACID SALT OF RUCAPARIB AND METHOD OF PREPARING OF TRICYCLIC COMPOUNDS, RUCAPARIB AND CRYSTALLINE OF CAMPHORSULFONIC ACID SALT OF RUCAPARIB
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, (2020/06/15)
A method of preparing a tricyclic compound of formula (I), comprising the step of converting a compound of formula (II) into a compound of formula (III); and hydrogenating the compound of formula (III) in the presence of hydrogenation catalyst and hydrogen to form the tricyclic compound of formula (I); wherein R1 is H or a C1-3 alkyl group; and R2 is H, a halogen element or a C1-3 alkyl group.