ChemicalBook >> CAS DataBase List >>2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]propanamide

2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]propanamide

CAS No.
290297-26-6
Chemical Name:
2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]propanamide
Synonyms
Netupitant;Netupitan;CID6451149;CID-6451149;CID 6451149;Ro 67-31898;Ro 67-31898/000;Netupitant(CID-6451149);NETUPITANT (RO 67-31898);2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-meth...
CBNumber:
CB71483126
Molecular Formula:
C30H32F6N4O
Molecular Weight:
578.59
MDL Number:
MFCD25976831
MOL File:
290297-26-6.mol
MSDS File:
SDS
Last updated:2024-10-09 17:25:53

2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]propanamide Properties

Melting point 156.2-160.0 °C
Boiling point 597.4±50.0 °C(Predicted)
Density 1.255
storage temp. 2-8°C
solubility Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
pka 7.89±0.38(Predicted)
form Solid
color White to Off-White
InChIKey WAXQNWCZJDTGBU-UHFFFAOYSA-N
SMILES C(N(C)C1=C(C2C=CC=CC=2C)C=C(N2CCN(C)CC2)N=C1)(=O)C(C1C=C(C(F)(F)F)C=C(C(F)(F)F)C=1)(C)C
FDA UNII 7732P08TIR
NCI Drug Dictionary netupitant

SAFETY

Risk and Safety Statements

Symbol(GHS)  GHS hazard pictograms
GHS07
Signal word  Warning
Hazard statements  H315-H319
Precautionary statements  P302+P352-P305+P351+P338
NFPA 704
0
2 0

2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]propanamide price More Price(42)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Sigma-Aldrich SML2755 Netupitant ≥98% (HPLC) 290297-26-6 10MG $97.7 2024-03-01 Buy
Sigma-Aldrich SML2755 Netupitant ≥98% (HPLC) 290297-26-6 50MG $395 2024-03-01 Buy
Cayman Chemical 23809 Netupitant ≥98% 290297-26-6 10mg $89 2024-03-01 Buy
Cayman Chemical 23809 Netupitant ≥98% 290297-26-6 25mg $167 2024-03-01 Buy
Cayman Chemical 23809 Netupitant ≥98% 290297-26-6 50mg $267 2024-03-01 Buy
Product number Packaging Price Buy
SML2755 10MG $97.7 Buy
SML2755 50MG $395 Buy
23809 10mg $89 Buy
23809 25mg $167 Buy
23809 50mg $267 Buy

2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]propanamide Chemical Properties,Uses,Production

Description

Netupitant, originally developed by Helsinn Healthcare and later licensed to Eisai, Inc., was approved in the USA in October 2014 for the treatment of chemotherapy-induced nausea and emesis. Akynzeo ® is a fixed-dose combination of the new drug netupitant and the previously-approved 5-HT3 antagonist palonosetron. While palonosetron obtained approval previously for treating nausea and emesis occurring within the first 24 hours (acute phase) after chemotherapy, netupitant provides a synergistic effect with palonosetron, assisting in prevention of nausea and emesis in later stages following chemotherapy (25–120 h after chemotherapy treatment). Several clinical trials showed that this combination of netupitant and palonosetron (Akynzeo ?), in comparison to treatment with palonosetron treatment alone, led to an improved percentage of patients in all phases who did not experience any nausea and emesis after undergoing chemotherapy. Netupitant itself joins the class of selective Neurokinin- 1 (NK1) receptor antagonists which, in addition to their use for treating chemotherapy-induced nausea and emesis, also play an important role as therapies for depression and anxiety.

Description

Netupitant is an insurmountable antagonist of the neurokinin-1 (NK1) receptor (Ki = 0.95 nM in CHO cells expressing the human recombinant receptor). It is selective for human NK1 over human NK2 and NK3 and rat NK1 (Kis = >1,500 nM) and over 50 G protein-coupled receptors, monoamine transporters, and ion channels when used in the nanomolar range. Netupitant decreases the maximal response to substance P-induced contractions in isolated guinea pig ileum with long-lasting effects. It also dose-dependently inhibits the substance P-induced scratching, biting, and licking response in mice when used at doses ranging from 1-10 mg/kg and decreases NK agonist-induced foot tapping in gerbils (ID50s = 1.5 mg/kg, i.p., or 0.5 mg/kg, oral). Formulations containing netupitant have been used in the treatment of chemotherapy-induced nausea and vomiting.

Uses

Antiemetic.

Uses

Netupitant is a potent and selective neurokinin-1 receptor (NK1) receptor antagonist. It is achiral and orally active.

Definition

ChEBI: A monocarboxylic acid amide obtained by 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; an antiemetic used in combination with palonosetron hydrochloride (under the trade name Akynzeo) to treat nausea and vomiting in patients undergoing cancer chemotherapy.

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).

Synthesis_290297-26-6

290297-25-5
289686-69-7
290297-26-6
Synthesis of 2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]propanamide from 3-PYRIDINAMINE, N-METHYL-4-(2-METHYLPHENYL)-6-(4-METHYL-1-PIPERAZINYL)- and 2-(3,5-bis-trifluoromethylphenyl)-2-methyl-propionyl chloride
Global( 190)Suppliers
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Aceschem Inc.
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Hebei Chuanghai Biotechnology Co,.LTD
+86-13131129325 sales1@chuanghaibio.com China 5893 58
shandong perfect biotechnology co.ltd
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BEIJING SJAR TECHNOLOGY DEVELOPMENT CO., LTD.
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Watson Biotechnology Co.,Ltd
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Beijing Cooperate Pharmaceutical Co.,Ltd
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Henan Tianfu Chemical Co.,Ltd.
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ATK CHEMICAL COMPANY LIMITED
+undefined-21-51877795 ivan@atkchemical.com China 32951 60
TianYuan Pharmaceutical CO.,LTD
+86-755-23284190 13684996853 sales@tianpharm.com CHINA 304 58
BOC Sciences
+1-631-485-4226 inquiry@bocsci.com United States 19553 58

View Lastest Price from 2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]propanamide manufacturers

Image Update time Product Price Min. Order Purity Supply Ability Manufacturer
Netupitan pictures 2024-11-07 Netupitan
290297-26-6
US $0.00-0.00 / G 10G 99% 10KG Watson Biotechnology Co.,Ltd
Netupitant  pictures 2024-11-06 Netupitant
290297-26-6
US $0.00 / g 1g More Than 99% 100kg/Month BEIJING SJAR TECHNOLOGY DEVELOPMENT CO., LTD.
 Netupitant pictures 2024-10-11 Netupitant
290297-26-6
US $77.60 / KG 1KG 99% 5000kg Hebei Chuanghai Biotechnology Co,.LTD
  • Netupitan pictures
  • Netupitan
    290297-26-6
  • US $0.00-0.00 / G
  • 99%
  • Watson Biotechnology Co.,Ltd
  • Netupitant  pictures
  • Netupitant
    290297-26-6
  • US $0.00 / g
  • More Than 99%
  • BEIJING SJAR TECHNOLOGY DEVELOPMENT CO., LTD.
  •  Netupitant pictures
  • Netupitant
    290297-26-6
  • US $77.60 / KG
  • 99%
  • Hebei Chuanghai Biotechnology Co,.LTD

2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]propanamide Spectrum

2-[3,5-Bis(trifluoromethyl)phenyl]-N-[6-(4-methylpiperazin-1-yl)-4-(o-tolyl)pyridin-3-yl]-N-methylisobutyramide 2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]propanamide Ro 67-31898/000 2-(3,5-bis(trifluoroMethyl)phenyl)-N,2- diMethyl-N-(6-(4-Methylpiperazin-1-yl)-4- o-tolylpyridin-3-yl)propanaMide BenzeneacetaMide, N,a,a-triMethyl-N-[4-(2-Methylphenyl)-6-(4-Methyl-1-piperazinyl)-3-pyridinyl]-3,5-bis(trifluoroMethyl)- 2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3- Ro 67-31898 Netupitan CID 6451149 CID6451149 CID-6451149 Netupitant(CID-6451149) 2-[3,5-Bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methylpiperazin-1-y NETUPITANT (RO 67-31898) Benzeneacetamide, N,α,α-trimethyl-N-[4-(2-methylphenyl)-6-(4-methyl-1-piperazinyl)-3-pyridinyl]-3,5-bis(trifluoromethyl)- 2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-meth... NetupitantQ: What is Netupitant Q: What is the CAS Number of Netupitant Q: What is the storage condition of Netupitant Q: What are the applications of Netupitant Netupitant 290297-26-6 290297-36-6 C30H32F6N4O