290297-26-6 Usage
Description
2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]propanamide is a complex organic compound with a unique chemical structure. It is a monocarboxylic acid amide derived from the formal condensation of the carboxy group of 2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoic acid with the secondary amino group of N-methyl-4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-amine.
Uses
Used in Pharmaceutical Industry:
2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]propanamide is used as an antiemetic agent for the treatment of nausea and vomiting in patients undergoing cancer chemotherapy. It is used in combination with palonosetron hydrochloride under the trade name Akynzeo.
Used in Cancer Treatment:
In the pharmaceutical industry, 2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]propanamide is used as a potent and selective neurokinin-1 receptor (NK1) receptor antagonist. It provides a synergistic effect with palonosetron, assisting in the prevention of nausea and emesis in later stages (25–120 hours) following chemotherapy treatment. This combination leads to an improved percentage of patients in all phases who do not experience any nausea and emesis after undergoing chemotherapy.
Additionally, it is an insurmountable antagonist of the neurokinin-1 (NK1) receptor and is selective for human NK1 over other receptors. It has been shown to decrease the maximal response to substance P-induced contractions and inhibit substance P-induced responses in mice and gerbils, making it a potential candidate for therapies beyond chemotherapy-induced nausea and emesis, such as depression and anxiety treatments.
Synthesis
The most likely process-scale synthesis
of netupitant begins with 6-chloronicotinic acid (185). From
185, a one-pot 1,4-Grignard addition/oxidation reaction, developed
to provide an improved route to NK1 receptor antagonists, was
employed for direct installation of the C4-o-tolyl substituent. Using
this procedure, treatment of 6-chloronicotinic acid (185) with otolyl
magnesium chloride and subsequent oxidation with Mn
(OAc)2 in THF/AcOH generated the o-tolyl nicotinic acid intermediate
187 in 51% overall yield. From this intermediate, a one-pot
amide formation could be realized in high yield by conversion of
the acid to the corresponding acyl chloride and addition of NH4OH
(95% yield). Chloride displacement with 1-methyl piperazine under
heating conditions provided intermediate 189 in 95% yield.
Employing Hoffman reaction conditions originally reported by
Senanayake,171 rearrangement of amide 189 with NBS/NaOMe/
MeOH enabled formation of carbamate 190 in quantitative yield.
Reduction of the carbamate with Red-Al provided the desired
mono-methylated amine. To access the final drug target, acylation
of the intermediate methyl amine with 2-(3,5-bis(trifluoromethyl)
phenyl)-2-methylpropanoyl chloride (191) provided the final drug
netupitant (XXII) in 81% yield. In this case, due to the cost of 193,
the acid precursor to 191, and starting materials previously
reported for generating 191/193, as well as issues with isolation
of pure intermediates on scale, a novel route to 191 and 193 was
also developed during this synthesis, beginning with the inexpensive
and readily available bromide 192. This 2-step synthesis of 193 includes Grignard
reagent formation, quenching with acetone to yield the intermediary
tertiary alcohol, and subsequent carbonylation (TfOH, H2O, CO then NaOH/H2O) to provide 2-(3,5-bis(trifluoromethyl)-phenyl)-2-
methylpropanoic acid 193. Finally, conversion of acid 193 to the
acyl chloride with oxalyl chloride in DCM provided the necessary
acyl chloride 191 in quantitative yield (86% purity).
Check Digit Verification of cas no
The CAS Registry Mumber 290297-26-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,9,0,2,9 and 7 respectively; the second part has 2 digits, 2 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 290297-26:
(8*2)+(7*9)+(6*0)+(5*2)+(4*9)+(3*7)+(2*2)+(1*6)=156
156 % 10 = 6
So 290297-26-6 is a valid CAS Registry Number.
InChI:InChI=1/C30H32F6N4O/c1-19-8-6-7-9-23(19)24-17-26(40-12-10-38(4)11-13-40)37-18-25(24)39(5)27(41)28(2,3)20-14-21(29(31,32)33)16-22(15-20)30(34,35)36/h6-9,14-18H,10-13H2,1-5H3
290297-26-6Relevant articles and documents
Method for preparing netupitant
-
, (2018/04/02)
The invention discloses a method for preparing netupitant, and belongs to the field of medicine compounds. The method includes the steps: performing condensation on 2-chloro-5-aminopyridine and formicacid; performing reduction, Boc protection and iodination; performing coupling and deprotection and then performing condensation on products and 2-(3, 5-bis-trifluoromethyl-phenyl)-2-methyl propionicacid; performing substitution on products and N-methylpiperazine to obtain the netupitant. The method has the advantages that the steps of processes for preparing the netupitant have fewer side effects, the method is high in yield and less in environmental pollution, after-treatment is simple, and the netupitant which is a product prepared by the aid of the method is high in purity and low in individual impurity content.
4-(5-(2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethylpropanamido)-4-(o-tolyl)pyridin-2-yl)-1-methyl-1-((phosphonooxy)methyl)piperazin-1-ium as a neurokinin receptor modulator
-
, (2016/08/29)
Compounds and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the neurokinin (NK1) receptor, based on 4-(5-(2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethylpropanamido)-4-(o-tolyl)3yridine-2-yl)-1-methyl-1-((phosphonooxy)methyl)piperazin-1-ium and pharmaceutically acceptable salts thereof.
SUBSTITUTED 4-PHENYL-PYRIDINES FOR TREATMENT OF NK-1 RECEPTOR RELATED DISEASES
-
, (2018/10/31)
PROBLEM TO BE SOLVED: To provide new derivatives of 4-phenyl-pyridine compounds that are effective NK1 receptor antagonists, with enhanced physicochemical and/or biological properties, and methods for producing the 4-phenyl-pyridine compounds. SOLUTION: Disclosed are compounds, compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the neurokinin (NKj) receptor. The compounds have the general formula (I). COPYRIGHT: (C)2015,JPOandINPIT