1256589-74-8 Usage
Description
9-Ethyl-6,6-dimethyl-8-(4-morpholinopiperidin-1-yl)-11-oxo-5a,6,11,11a-tetrahydro-5H-benzo[b]carbazole-3-carbonitrile hydrochloride, also known as CH5424802 hydrochloride, is a potent and selective anaplastic lymphoma kinase (ALK) inhibitor. It is capable of blocking the resistant gatekeeper mutant, which results in reduced cell growth. 9-Ethyl-6,6-dimethyl-8-(4-morpholinopiperidin-1-yl)-11-oxo-5a,6,11,11a-tetrahydro-5H-benzo[b]carbazole-3-carbonitrile hydrochloride is also an intermediate of Alectinib (C183360), another highly selective and potent ALK inhibitor.
Used in Pharmaceutical Industry:
9-Ethyl-6,6-dimethyl-8-(4-morpholinopiperidin-1-yl)-11-oxo-5a,6,11,11a-tetrahydro-5H-benzo[b]carbazole-3-carbonitrile hydrochloride is used as an intermediate in the development of Alectinib hydrochloride, a second-generation ALK inhibitor. Alectinib hydrochloride, developed by Chugai Pharmaceutical/Hoffman-La Roche under the trade name Alecensa, was approved in Japan in April 2014 for the treatment of anaplastic lymphoma kinase (ALK) fusion-gene positive, unresectable, advanced, or recurrent non-small cell lung cancer (NSCLC). It has been granted orphan drug designation in Japan after showing a 93.5% objective response rate in phase II clinical trials and a 76% 2-year progression-free survival rate. Alectinib has shown significant promise for overcoming drug resistance developed with other ALK inhibitors, providing rapid treatment response time in a majority of patients.
Synthesis
The synthetic route to alectinib as reported by Chugai
begins with 7-methoxy-2-tetralone (1). Bis-methylation
with tetrabutylammonium hydrogen sulfide (TBAHS)/aq KOH/MeI
followed by bromination with N-bromosuccinimide (NBS) provided
the bromo-tetralone 2 in 67% yield over the two steps. Further
reaction of 2 with 3-hydrazinobenzonitrile/trifluoroacetic acid (TFA) led to formation of the desired Fischer indole product,
albeit as a 1:1 mixture of regioisomers (3/4), which were carried
forward as a mixture to oxidation with 2,3-dichloro-5,6-dicyano-
1,4-benzoquinone (DDQ).
Check Digit Verification of cas no
The CAS Registry Mumber 1256589-74-8 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,2,5,6,5,8 and 9 respectively; the second part has 2 digits, 7 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 1256589-74:
(9*1)+(8*2)+(7*5)+(6*6)+(5*5)+(4*8)+(3*9)+(2*7)+(1*4)=198
198 % 10 = 8
So 1256589-74-8 is a valid CAS Registry Number.
1256589-74-8Relevant articles and documents
IMPROVED PROCESS FOR THE PREPARATION OF 9-ETHYL-6,6-DIMETHYL-8-[4-(MORPHOLIN-4-YL) PIPERIDIN-1-YL]-11-OXO-6,11-DIHYDRO-5H-BENZO[B]CARBAZOLE-3-CARBONITRILE HYDROCHLORIDE
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Page/Page column 22-24; 27-28, (2019/11/19)
The present invention relates to novel process for the preparation of 9-ethyl-6,6-dimethyl-8-[4-(morpholin-4-yl)piperidin-1-yl]-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile hydrochloride compound of formula-1a, represented by the following structural formula: The present invention also provides an improved process for the preparation of tert-butyl-4-(4-ethyl-3-iodophenyl)-4-methyl-3-oxopentanoate having the following structural formula which is useful in the preparation of Alectinib and its pharmaceutical acceptable salts.
AMORPHOUS FORM OF TETRACYCLIC COMPOUND
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Paragraph 0120; 0121; 0123; 0124, (2017/08/26)
An amorphous form of 9-ethyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile and a solid dispersion containing the amorphous form can be used extremely advantageously as drugs for oral administration.
