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

Product Name
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;Ro 67-31898;CID-6451149;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
Formula Weight
578.59
MOL File
290297-26-6.mol
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2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]propanamide Property

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
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Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Warning
Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

Precautionary statements

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

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N-Bromosuccinimide Price

Sigma-Aldrich
Product number
SML2755
Product name
Netupitant
Purity
≥98% (HPLC)
Packaging
10MG
Price
$97.7
Updated
2024/03/01
Sigma-Aldrich
Product number
SML2755
Product name
Netupitant
Purity
≥98% (HPLC)
Packaging
50MG
Price
$395
Updated
2024/03/01
Cayman Chemical
Product number
23809
Product name
Netupitant
Purity
≥98%
Packaging
10mg
Price
$89
Updated
2024/03/01
Cayman Chemical
Product number
23809
Product name
Netupitant
Purity
≥98%
Packaging
25mg
Price
$167
Updated
2024/03/01
Cayman Chemical
Product number
23809
Product name
Netupitant
Purity
≥98%
Packaging
50mg
Price
$267
Updated
2024/03/01
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2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]propanamide Chemical Properties,Usage,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

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

Uses

Antiemetic.

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).

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

Raw materials

Preparation Products

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

China 165 China Hong Kong 1 India 11 Switzerland 1 United States 16 Global 194
Deyang Chengchuang Pharmaceutical Technology Co., Ltd.
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028-66569636 18227172063
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028-66569636
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sales@dyccpharma.com
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China
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Harway Pharma CO., LTD
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18254622207
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0546-5180666
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sales@harwaypharma.com
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China
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Foshan Junzheng Biotechnology Co., Ltd
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17813018085
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181367029@qq.com
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China
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Shanghai Boyle Chemical Co., Ltd.
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86-21-57758967
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sales@boylechem.com
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China
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J & K SCIENTIFIC LTD.
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010-82848833 400-666-7788
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86-10-82849933
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jkinfo@jkchemical.com
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China
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Chemvon Biotechnology Co., Ltd
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021-50790412
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+86-21-50790419
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info@chemvon.com
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Chembest Research Laboratories Limited
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+86-21-20908456
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021-58180499
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sales@BioChemBest.com
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China
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BOC Sciences
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1-631-485-4226; 16314854226
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United States
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Dalian Meilun Biotech Co., Ltd.
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0411-62910999 13889544652
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sales@meilune.com
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China
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Haoyuan Chemexpress Co., Ltd.
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021-58950125
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(86) 21-58955996
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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

Watson Biotechnology Co.,Ltd
Product
Netupitan 290297-26-6
Price
US $0.00-0.00/G
Min. Order
10G
Purity
99%
Supply Ability
10KG
Release date
2024-10-09
BEIJING SJAR TECHNOLOGY DEVELOPMENT CO., LTD.
Product
Netupitant 290297-26-6
Price
US $0.00/g
Min. Order
1g
Purity
More Than 99%
Supply Ability
100kg/Month
Release date
2024-09-19
shandong perfect biotechnology co.ltd
Product
Netupitant 290297-26-6
Price
US $0.00/g
Min. Order
1g
Purity
98% HPLC
Supply Ability
100kg
Release date
2023-08-14

290297-26-6, 2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]propanamideRelated Search:

Methyl (6-(4-Methylpiperazin-1-yl)-4-(o-tolyl)pyridin-3-yl)carbaMate 3-PYRIDINAMINE, N-METHYL-4-(2-METHYLPHENYL)-6-(4-METHYL-1-PIPERAZINYL)- 3-PYRIDINECARBOXAMIDE, 4-(2-METHYLPHENYL)-6-(4-METHYL-1-PIPERAZINYL)- N-tert-butyl-6-chloro-4-(o-tolyl)nicotinamide Sulfachoropyrazine sodium Pyrazinamide Indole Furan Pyridoxine Pyrazole Oxazole Pyrrole Pyridine

  • 2-[3,5-Bis(trifluoromethyl)phenyl]-N-[6-(4-methylpiperazin-1-yl)-4-(o-tolyl)pyridin-3-yl]-N-methylisobutyramide
  • Netupitant
  • 2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]propanamide
  • NETUPITANT (RO 67-31898)
  • 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
  • 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
  • 290297-26-6
  • 290297-36-6
  • C30H32F6N4O